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Cryo-EM structure of glycoprotein C from Crimean-Congo hemorrhagic fever virus
Na Li, Guibo Rao, Zhiqiang Li, Jiayi Yin, Tingting Chong, Kexing Tian, Yan Fu, Sheng Cao
收稿日期: 2021-10-25 录用日期: 2020-11-12 出版日期: 2021-11-26
Crimean-Congo hemorrhagic fever virus (CCHFV) is a causative agent of serious hemorrhagic diseases in humans with high mortality rates. CCHFV glycoprotein Gc plays critical roles in mediating virus-host membrane fusion and has been studied extensively as an immunogen. However, the molecular mechanisms involved in membrane fusion and Gc-specific antibody-antigen interactions remain unresolved largely because structural information of this glycoprotein is missing. We designed a trimeric protein including most of the ectodomain region of Gc from the prototype CCHFV strain, IbAr10200, which enabled the cryo-electron microscopy structure to be solved at a resolution of 2.8 Å. The structure confirms that CCHFV Gc is a class Ⅱ fusion protein. Unexpectedly, structural comparisons with other solved Gc trimers in the postfusion conformation revealed that CCHFV Gc adopts hybrid architectural features of the fusion loops from hantaviruses and domain Ⅲ from phenuiviruses, suggesting a complex evolutionary pathway among these bunyaviruses. Antigenic sites on CCHFV Gc that protective neutralizing antibodies target were mapped onto the CCHFV Gc structure, providing valuable information that improved our understanding of potential neutralization mechanisms of various antibodies.Crimean-Congo hemorrhagic fever virus (CCHFV) is a causative agent of serious hemorrhagic diseases in humans with high mortality rates. CCHFV glycoprotein Gc plays critical roles in mediating virus-host membrane fusion and has been studied extensively as an immunogen. However, the molecular mechanisms involved in membrane fusion and Gc-specific antibody-antigen interactions remain unresolved largely because structural information of this glycoprotein is missing. We designed a trimeric protein including most of the ectodomain region of Gc from the prototype CCHFV strain, IbAr10200, which enabled the cryo-electron microscopy structure to be solved at a resolution of 2.8 Å. The structure confirms that CCHFV Gc is a class Ⅱ fusion protein. Unexpectedly, structural comparisons with other solved Gc trimers in the postfusion conformation revealed that CCHFV Gc adopts hybrid architectural features of the fusion loops from hantaviruses and domain Ⅲ from phenuiviruses, suggesting a complex evolutionary pathway among these bunyaviruses. Antigenic sites on CCHFV Gc that protective neutralizing antibodies target were mapped onto the CCHFV Gc structure, providing valuable information that improved our understanding of potential neutralization mechanisms of various antibodies.
A new luciferase immunoprecipitation system assay provided serological evidence for missed diagnosis of severe fever with thrombocytopenia syndrome
Shengyao Chen, Minjun Xu, Xiaoli Wu, Yuan Bai, Junming Shi, Min Zhou, Qiaoli Wu, Shuang Tang, Fei Deng, Bo Qin, Shu Shen
收稿日期: 2021-08-11 录用日期: 2021-10-12 出版日期: 2021-11-26
Severe fever with thrombocytopenia syndrome (SFTS), caused by SFTS virus (SFTSV) infection, was first reported in 2010 in China with an initial fatality of up to 30%. The laboratory confirmation of SFTSV infection in terms of detection of viral RNA or antibody levels is critical for SFTS diagnosis and therapy. In this study, a new luciferase immunoprecipitation system (LIPS) assay based on pREN2 plasmid expressing SFTSV NP gene and tagged with Renilla luciferase (Rluc), was established and used to investigate the levels of antibody responses to SFTSV. Totally 464 serum samples from febrile patients were collected in the hospital of Shaoxing City in Zhejiang Province in 2019. The results showed that 82 of the 464 patients (17.7%) had antibody response to SFTSV, which were further supported by immunofluorescence assays (IFAs). Further, qRT-PCR and microneutralization tests showed that among the 82 positive cases, 15 patients had viremia, 10 patients had neutralizing antibody, and one had both (totally 26 patient). However, none of these patients were diagnosed as SFTS in the hospital probably because of their mild symptoms or subclinical manifestations. All the results indicated that at least the 26 patients having viremia or neutralizing antibody were the missed diagnosis of SFTS cases. The findings suggested the occurrence of SFTS and the SFTS incidence were higher than the reported level in Shaoxing in 2019, and that LIPS may provide an alternative strategy to confirm SFTSV infection in the laboratory.Severe fever with thrombocytopenia syndrome (SFTS), caused by SFTS virus (SFTSV) infection, was first reported in 2010 in China with an initial fatality of up to 30%. The laboratory confirmation of SFTSV infection in terms of detection of viral RNA or antibody levels is critical for SFTS diagnosis and therapy. In this study, a new luciferase immunoprecipitation system (LIPS) assay based on pREN2 plasmid expressing SFTSV NP gene and tagged with Renilla luciferase (Rluc), was established and used to investigate the levels of antibody responses to SFTSV. Totally 464 serum samples from febrile patients were collected in the hospital of Shaoxing City in Zhejiang Province in 2019. The results showed that 82 of the 464 patients (17.7%) had antibody response to SFTSV, which were further supported by immunofluorescence assays (IFAs). Further, qRT-PCR and microneutralization tests showed that among the 82 positive cases, 15 patients had viremia, 10 patients had neutralizing antibody, and one had both (totally 26 patient). However, none of these patients were diagnosed as SFTS in the hospital probably because of their mild symptoms or subclinical manifestations. All the results indicated that at least the 26 patients having viremia or neutralizing antibody were the missed diagnosis of SFTS cases. The findings suggested the occurrence of SFTS and the SFTS incidence were higher than the reported level in Shaoxing in 2019, and that LIPS may provide an alternative strategy to confirm SFTSV infection in the laboratory.
Tilorone confers robust in vitro and in vivo antiviral effects against severe fever with thrombocytopenia syndrome virus
Jingjing Yang, Yunzheng Yan, Qingsong Dai, Jiye Yin, Lei Zhao, Yuexiang Li, Wei Li, Wu Zhong, Ruiyuan Cao, Song Li
收稿日期: 2021-09-08 录用日期: 2021-11-25 出版日期: 2021-11-25
Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging pathogen, is a tick-borne bunyavirus belonging to the genus Bandavirus in the family Phenuiviridae (Kuhn et al. 2020). This pathogen was first identified in China during the heightened surveillance of acute febrile illness in 2009, and has been reported to cause several outbreaks in eastern Asia areas, including China, Japan, and Korea (Yu et al. 2011). Besides, Vietnam has also reported several confirmed SFTS cases (Tran et al. 2019). The mortality rate in hospitalised patients with SFTSV infection is up to 10%–30%. Moreover, SFTSV has been reported to possibly transmitted by the contact of body fluids from person-to-person, and extensive SFTSV contamination was detected in the patient rooms (Kim et al. 2015). These reports suggest that more stringent isolation measures are needed for the prevention of massive SFTSV outbreak.Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging pathogen, is a tick-borne bunyavirus belonging to the genus Bandavirus in the family Phenuiviridae (Kuhn et al. 2020). This pathogen was first identified in China during the heightened surveillance of acute febrile illness in 2009, and has been reported to cause several outbreaks in eastern Asia areas, including China, Japan, and Korea (Yu et al. 2011). Besides, Vietnam has also reported several confirmed SFTS cases (Tran et al. 2019). The mortality rate in hospitalised patients with SFTSV infection is up to 10%–30%. Moreover, SFTSV has been reported to possibly transmitted by the contact of body fluids from person-to-person, and extensive SFTSV contamination was detected in the patient rooms (Kim et al. 2015). These reports suggest that more stringent isolation measures are needed for the prevention of massive SFTSV outbreak.
A single nonsynonymous mutation on ZIKV E protein-coding sequences leads to markedly increased neurovirulence in vivo
Zhihua Liu, Yawei Zhang, Mengli Cheng, Ningning Ge, Jiayi Shu, Zhiheng Xu, Xiao Su, Zhihua Kou, Yigang Tong, Chengfeng Qin, Xia Jin
收稿日期: 2021-09-09 录用日期: 2021-10-20 出版日期: 2021-11-17
Zika virus (ZIKV) can infect a wide range of tissues including the developmental brain of human fetus. Whether specific viral genetic variants are linked to neuropathology is incompletely understood. To address this, we have intracranially serially passaged a clinical ZIKV isolate (SW01) in neonatal mice and discovered variants that exhibit markedly increased virulence and neurotropism. Deep sequencing analysis combining with molecular virology studies revealed that a single 67D (Aspartic acid) to N (Asparagine) substitution on E protein is sufficient to confer the increased virulence and neurotropism in vivo. Notably, virus clones with D67N mutation had higher viral production and caused more severe cytopathic effect (CPE) in human neural astrocytes U251 cells in vitro, indicating its potential neurological toxicity to human brain. These findings revealed that a single mutation D67N on ZIKV envelope may lead to severe neuro lesion that may help to explain the neurovirulence of ZIKV and suggest monitoring the occurrence of this mutation during nature infection maybe important.Zika virus (ZIKV) can infect a wide range of tissues including the developmental brain of human fetus. Whether specific viral genetic variants are linked to neuropathology is incompletely understood. To address this, we have intracranially serially passaged a clinical ZIKV isolate (SW01) in neonatal mice and discovered variants that exhibit markedly increased virulence and neurotropism. Deep sequencing analysis combining with molecular virology studies revealed that a single 67D (Aspartic acid) to N (Asparagine) substitution on E protein is sufficient to confer the increased virulence and neurotropism in vivo. Notably, virus clones with D67N mutation had higher viral production and caused more severe cytopathic effect (CPE) in human neural astrocytes U251 cells in vitro, indicating its potential neurological toxicity to human brain. These findings revealed that a single mutation D67N on ZIKV envelope may lead to severe neuro lesion that may help to explain the neurovirulence of ZIKV and suggest monitoring the occurrence of this mutation during nature infection maybe important.
Nano-bubble hydrogen water: an effective therapeutic agent against inflammation related disease caused by viral infection in zebrafish model
Chen Li, Yiran Cao, Fukuda Kohei, Haihong Hao, Guiqing Peng, Can Cheng, Jing Ye
收稿日期: 2021-06-09 录用日期: 2021-10-08 出版日期: 2021-11-16
Since the anti-inflammatory effect of hydrogen has been widely known, it was supposed that hydrogen could suppress tissue damage by inhibiting virus-related inflammatory reactions. However, hydrogen is slightly soluble in water, which leads to poor effect of oral hydrogen-rich water therapy. In this study, the nano-bubble hydrogen water (nano-HW) (about 0.7 ppm) was prepared and its therapeutic effect against viral infection was investigated by utilizing spring viraemia of carp virus (SVCV)-infected zebrafish as model. Three-month-old zebrafish were divided into nano-HW treatment–treated group and aquaculture water treated group (control group). The results revealed that the cumulative mortality rate of SVCV-infected zebrafish was reduced by 40% after treatment with nano-bubble hydrogen water, and qRT-PCR results showed that SVCV replication was significantly inhibited. H&E staining showed that SVCV infection caused tissue damage was greatly alleviated after treatment with nano-bubble hydrogen water. Futhermore, SVCV infection caused reactive oxygen species (ROS) accumulation was significantly reduced upon nano-HW treatment. The level of proinflammatory cytokines IL-1β, IL-8, and TNF-α was remarkably reduced in the nano-HW-treated group in vivo and in vitro. Taken together, our data demonstrated for the first time that nano-HW could inhibit the inflammatory response caused by viral infection in zebrafish, which suggests that nano-HW can be applied to antiviral research, and provides a novel therapeutic strategy for virus-caused inflammation related disease.Since the anti-inflammatory effect of hydrogen has been widely known, it was supposed that hydrogen could suppress tissue damage by inhibiting virus-related inflammatory reactions. However, hydrogen is slightly soluble in water, which leads to poor effect of oral hydrogen-rich water therapy. In this study, the nano-bubble hydrogen water (nano-HW) (about 0.7 ppm) was prepared and its therapeutic effect against viral infection was investigated by utilizing spring viraemia of carp virus (SVCV)-infected zebrafish as model. Three-month-old zebrafish were divided into nano-HW treatment–treated group and aquaculture water treated group (control group). The results revealed that the cumulative mortality rate of SVCV-infected zebrafish was reduced by 40% after treatment with nano-bubble hydrogen water, and qRT-PCR results showed that SVCV replication was significantly inhibited. H&E staining showed that SVCV infection caused tissue damage was greatly alleviated after treatment with nano-bubble hydrogen water. Futhermore, SVCV infection caused reactive oxygen species (ROS) accumulation was significantly reduced upon nano-HW treatment. The level of proinflammatory cytokines IL-1β, IL-8, and TNF-α was remarkably reduced in the nano-HW-treated group in vivo and in vitro. Taken together, our data demonstrated for the first time that nano-HW could inhibit the inflammatory response caused by viral infection in zebrafish, which suggests that nano-HW can be applied to antiviral research, and provides a novel therapeutic strategy for virus-caused inflammation related disease.
Updates on CRISPR-based gene editing in HIV-1/AIDS therapy
Zhihao Zhang, Wei Hou, Shuliang Chen
收稿日期: 2021-08-11 录用日期: 2021-11-10 出版日期: 2021-11-15
Although tremendous efforts have been made to prevent and treat HIV-1 infection, HIV-1/AIDS remains a major threat to global human health. The combination antiretroviral therapy (cART), although able to suppress HIV-1 replication, cannot eliminate the proviral DNA integrated into the human genome and thus requires lifelong treatment that may lead to various side effects. In recent years, clustered regularly interspaced short palindromic repeat (CRISPR)-associated nuclease 9 (Cas9) related gene-editing systems have been developed and designed as effective ways to treat HIV-1 infection. However, new gene-targeting tools derived from or functioning like CRISPR/Cas9, including base editor, prime editing, SHERLOCK, DETECTR, PAC-MAN, ABACAS, pfAGO, have been developed and optimized for pathogens detection and diseases correction. Here, we summarize recent studies on HIV-1/AIDS gene therapy and provide more gene-editing targets based on studies relating to the molecular mechanism of HIV-1 infection. We also identify the strategies and potential applications of these new gene-editing technologies for HIV-1/AIDS treatment in the future. Moreover, we discuss- the caveats and problems that should be addressed before the clinical use of these versatile CRISPR- based gene targeting tools. Finally, we offer alternative solutions to improve the practice of gene targeting in HIV-1/AIDS gene therapy.Although tremendous efforts have been made to prevent and treat HIV-1 infection, HIV-1/AIDS remains a major threat to global human health. The combination antiretroviral therapy (cART), although able to suppress HIV-1 replication, cannot eliminate the proviral DNA integrated into the human genome and thus requires lifelong treatment that may lead to various side effects. In recent years, clustered regularly interspaced short palindromic repeat (CRISPR)-associated nuclease 9 (Cas9) related gene-editing systems have been developed and designed as effective ways to treat HIV-1 infection. However, new gene-targeting tools derived from or functioning like CRISPR/Cas9, including base editor, prime editing, SHERLOCK, DETECTR, PAC-MAN, ABACAS, pfAGO, have been developed and optimized for pathogens detection and diseases correction. Here, we summarize recent studies on HIV-1/AIDS gene therapy and provide more gene-editing targets based on studies relating to the molecular mechanism of HIV-1 infection. We also identify the strategies and potential applications of these new gene-editing technologies for HIV-1/AIDS treatment in the future. Moreover, we discuss- the caveats and problems that should be addressed before the clinical use of these versatile CRISPR- based gene targeting tools. Finally, we offer alternative solutions to improve the practice of gene targeting in HIV-1/AIDS gene therapy.
Identification of a Novel Hepacivirus in Mongolian Gerbil (Meriones unguiculatus) from Shaanxi, China
Cui-hong An, Juan Li, Yi-ting Wang, Shou-min Nie, Wen-hui Chang, Hong Zhou, Lin Xu, Yang-xin Sun, Wei-feng Shi, Ci-xiu Li
收稿日期: 2021-07-28 录用日期: 2021-10-10 出版日期: 2021-11-05
Hepaciviruses, members of the family Flaviviridae, are enveloped viruses containing a single-stranded positive-sense RNA genome of approximately 8.9–10.5 kb in size (Simmonds et al. 2017). To date, 15 species (Hepacivirus A–N, and P) have been documented within the Hepacivirus genus that show distinct host ranges, including primates, bats, horses, donkeys, cows, and various rodents (Hartlage et al. 2016). Seven rodent-associated hepaciviruses have been characterized, including hepacivirus E, I, G and H infecting rodents of Muridae, hepacivirus F and J infecting rodents of Cricetidae (de Souza et al. 2019), and heapcivirus P infecting rodents of Xerinae (Li et al. 2019). Additional unclassified rodent hapaciviruses have been described in diverse rodents from Dormouse, Echimyidae, Heteromyidae, and Spalacidae. Mongolian gerbils (Meriones unguiculatus) are small rodents belonging to the family Muridae and are widely distributed in the desert grasslands and steppes of northern China, Mongolia, and Russia (Liu et al. 2007). They have been reported as a major host of Yersinia pestis causing plagues in China in recent decades (Riehm et al. 2011). Moreover, Mongolian gerbil is known to be susceptible to various viruses and is a commonly used animal model for virus research (Li et al. 2009). Despite this, the natural virome of wild Meriones unguiculatus has not been described. Herein, we reported the first hepacivirus detected in Mongolian gerbils captured in Dingbian County of Shaanxi Province, one of the plague zones in China.Hepaciviruses, members of the family Flaviviridae, are enveloped viruses containing a single-stranded positive-sense RNA genome of approximately 8.9–10.5 kb in size (Simmonds et al. 2017). To date, 15 species (Hepacivirus A–N, and P) have been documented within the Hepacivirus genus that show distinct host ranges, including primates, bats, horses, donkeys, cows, and various rodents (Hartlage et al. 2016). Seven rodent-associated hepaciviruses have been characterized, including hepacivirus E, I, G and H infecting rodents of Muridae, hepacivirus F and J infecting rodents of Cricetidae (de Souza et al. 2019), and heapcivirus P infecting rodents of Xerinae (Li et al. 2019). Additional unclassified rodent hapaciviruses have been described in diverse rodents from Dormouse, Echimyidae, Heteromyidae, and Spalacidae. Mongolian gerbils (Meriones unguiculatus) are small rodents belonging to the family Muridae and are widely distributed in the desert grasslands and steppes of northern China, Mongolia, and Russia (Liu et al. 2007). They have been reported as a major host of Yersinia pestis causing plagues in China in recent decades (Riehm et al. 2011). Moreover, Mongolian gerbil is known to be susceptible to various viruses and is a commonly used animal model for virus research (Li et al. 2009). Despite this, the natural virome of wild Meriones unguiculatus has not been described. Herein, we reported the first hepacivirus detected in Mongolian gerbils captured in Dingbian County of Shaanxi Province, one of the plague zones in China.
Novel pegiviruses infecting wild birds and rodents
Wentao Zhu, Jing Yang, Shan Lu, Yuyuan Huang, Dong Jin, Ji Pu, Liyun Liu, Zhenjun Li, Mang Shi, Jianguo Xu
收稿日期: 2021-08-30 录用日期: 2021-11-04 出版日期: 2021-11-04
Pegivirus (family Flaviviridae) is a genus of small enveloped RNA viruses that mainly causes blood infections in various mammals including human. Herein, we carried out an extensive survey of pegiviruses from a wide range of wild animals mainly sampled in the Qinghai-Tibet Plateau of China. Three novel pegiviruses, namely Passer montanus pegivirus, Leucosticte brandti pegivirus and Montifringilla taczanowskii pegivirus, were identified from different wild birds, and one new rodent pegivirus, namely Phaiomys leucurus pegivirus, was identified from Blyth’s vole. Interestingly, the pegiviruses of non-mammalian origin discovered in this study substantially broaden the host range of Pegivirus to avian species. Co-evolutionary analysis showed virus-host co-divergence over long evolutionary timescales, and indicated that pegiviruses largely followed a virus-host co-divergence relationship. Overall, this work extends the biodiversity of the Pegivirus genus to those infecting wild birds and hence revises the host range and evolutionary history of genus Pegivirus.Pegivirus (family Flaviviridae) is a genus of small enveloped RNA viruses that mainly causes blood infections in various mammals including human. Herein, we carried out an extensive survey of pegiviruses from a wide range of wild animals mainly sampled in the Qinghai-Tibet Plateau of China. Three novel pegiviruses, namely Passer montanus pegivirus, Leucosticte brandti pegivirus and Montifringilla taczanowskii pegivirus, were identified from different wild birds, and one new rodent pegivirus, namely Phaiomys leucurus pegivirus, was identified from Blyth’s vole. Interestingly, the pegiviruses of non-mammalian origin discovered in this study substantially broaden the host range of Pegivirus to avian species. Co-evolutionary analysis showed virus-host co-divergence over long evolutionary timescales, and indicated that pegiviruses largely followed a virus-host co-divergence relationship. Overall, this work extends the biodiversity of the Pegivirus genus to those infecting wild birds and hence revises the host range and evolutionary history of genus Pegivirus.
Epidemiological Evidence of Mosquito-Borne Viruses among Persons and Vectors in Iran: A Study from North to South
Abbas Ahmadi Vasmehjani, Farhad Rezaei, Mohammad Farahmand, Talat Mokhtari-Azad, Mohammad Reza Yaghoobi-Ershadi, Mohsen Keshavarz, Hamid Reza.Baseri, Morteza Zaim, Mahmood Iranpour, Habibollah Turki, Mohammad esmaeilpour-bandboni
收稿日期: 2020-07-12 录用日期: 2021-08-09 出版日期: 2021-10-22
The diversity and evolution of retroviruses: perspectives from viral “fossils”
Jialu Zheng, Yutong Wei, Guan-Zhu Han
收稿日期: 2021-08-18 录用日期: 2021-10-12 出版日期: 2021-10-22
Retroviruses exclusively infect vertebrates, causing a variety of diseases. The replication of retroviruses requires reverse transcription and integration into host genomes. When infecting germline cells, retroviruses become inherited vertically, forming endogenous retroviruses (ERVs). ERVs document past viral infections, providing molecular fossils for studying the evolutionary history of retroviruses. In this review, we summarize the recent advances in understanding the diversity and evolution of retroviruses from the perspectives of viral fossils, and discuss the effects of ERVs on the evolution of host biology.Retroviruses exclusively infect vertebrates, causing a variety of diseases. The replication of retroviruses requires reverse transcription and integration into host genomes. When infecting germline cells, retroviruses become inherited vertically, forming endogenous retroviruses (ERVs). ERVs document past viral infections, providing molecular fossils for studying the evolutionary history of retroviruses. In this review, we summarize the recent advances in understanding the diversity and evolution of retroviruses from the perspectives of viral fossils, and discuss the effects of ERVs on the evolution of host biology.
核仁素通过与兔出血症病毒RdRp,p16,p23相互作用促进病毒复制
朱杰, 缪秋红, 郭宏元, 汤傲星, 董丹丹, 唐井玉, 王芳, 童光志, 刘光清
收稿日期: 2021-06-23 录用日期: 2021-09-15 出版日期: 2021-10-19

兔出血症病毒(RHDV)是杯状病毒科的一员,不能在体外繁殖,阻碍了对其复制机制的研究进展。前期,我们构建了RHDV 复制子系统为探索RHDV 在细胞中的复制机理提供了一个平台。本研究借助该复制子系统,并利用两步亲和纯化,鉴定了与 RHDV 复制酶RdRp相关的宿主因子。我们发现宿主蛋白核仁素 (NCL) 与病毒RdRp 直接相互作用。同时,我们还发现 在RK-13细胞中,NCL 过表达显著增强RHDV的复制,而敲低NCL则严重破坏该病毒的复制。此外,我们还发现 NCL 与病毒非结构蛋白P16 和 P23 也存在直接相互作用。并且,敲低细胞内的NCL显著下调RdRp 与相关宿主因子的结合。这些结果表明宿主蛋白 NCL 对于 RHDV 复制是必不可少的,并且充当病毒复制酶和宿主蛋白之间的桥梁。

Rabbit hemorrhagic disease virus (RHDV) is a member of the Caliciviridae family and cannot be propagated in vitro, which has impeded the progress of investigating its replication mechanism. Construction of an RHDV replicon system has recently provided a platform for exploring RHDV replication in host cells. Here, aided by this replicon system and using twostep affinity purification, we purified the RHDV replicase and identified its associated host factors. We identified rabbit nucleolin (NCL) as a physical link, which mediating the interaction between other RNA-dependent RNA polymerase (RdRp)-related host proteins and the viral replicase RdRp. We found that the overexpression or knockdown of NCL significantly increased or severely impaired RHDV replication in RK-13 cells, respectively. NCL was identified to directly interact with RHDV RdRp, p16, and p23. Furthermore, NCL knockdown severely impaired the binding of RdRp to RdRp-related host factors. Collectively, these results indicate that the host protein NCL is essential for RHDV replication and acts as a physical link between viral replicase and host proteins.

An Integrated Rapid Nucleic Acid Detection Assay Based on Recombinant Polymerase Amplification for SARS-CoV-2
Ying Tang, Yiqin Wang, Yuchang Li, Huai Zhao, Sen Zhang, Ying Zhang, Jing Li, Yuehong Chen, Xiaoyan Wu, Chengfeng Qin, Tao Jiang, Xiaoping Kang
收稿日期: 2020-06-03 录用日期: 2020-06-16 出版日期: 2021-10-19
长江病毒宏基因组分析扩充了淡水中原核和真核生物病毒的多样性
芦娟, 杨世兴, 张潇丹, 汤祥明, 张聚, 王晓春, 王浩, 沈权, 张文
收稿日期: 2021-07-21 录用日期: 2021-09-03 出版日期: 2021-10-14

水生态系统中包含着极其丰富多样的病毒群,但目前对江河水中的病毒组成情况却知之甚少。本研究使用病毒宏基因组学方法探究了长江三角洲水域的病毒群特征,分析比较了6个采样点的病毒组。虽然各采样点病毒组在物种丰度上有细微差异,但总体上组成相似,均以有尾噬菌体目(Caudovirales)为主,并且淡水噬菌体种(Freshwater phage uvFW)也在各样本中普遍存在。位于南京的病毒群具有独特的组成特征,其中细小病毒科(Parvoviridae)的丰度较高。基于各病毒群特征基因的系统发育分析显示,有尾噬菌体目和CRESS-DNA病毒具有较高的遗传多样性。相反,微小噬菌体科(Microviridae)、细小病毒科(Parvoviridae)和核糖病毒域(Riboviria)的病毒相对保守。本研究首次揭示了大型江河生态系统中病毒群的组成结构及其多样性和保守性,有助于淡水资源的合理利用。

Viruses in aquatic ecosystems are characterized by extraordinary abundance and diversity. Thus far, there have been limited studies focused on viral communities in river water systems. Here, we investigated the virome of the Yangtze River Delta using viral metagenomic analysis. The compositions of viral communities from six sampling sites were analyzed and compared. By using library construction and next generation sequencing, contigs and singlet reads similar to viral sequences were classified into 17 viral families, including nine dsDNA viral families, four ssDNA viral families and four RNA viral families. Statistical analysis using Friedman test suggested that there was no significant difference among the six sampling sites (P > 0.05). The viromes in this study were all dominated by the order Caudovirales, and a group of Freshwater phage uvFW species were particularly prevalent among all the samples. The virome from Nanjing presented a unique pattern of viral community composition with a relatively high abundance of family Parvoviridae. Phylogenetic analyses based on virus hallmark genes showed that the Caudovirales order and CRESS-DNA viruses presented high genetic diversity, while viruses in the Microviridae and Parvoviridae families and the Riboviria realm were relatively conservative. Our study provided the first insight into viral community composition in large river ecosystem, revealing the diversity and stability of river water virome, contributing to the proper utilization of freshwater resource.

Immunogenicity of a Recombinant VSV-Vectored SARS-CoV Vaccine Induced Robust Immunity in Rhesus Monkeys after Single-Dose Immunization
Dan Shan, Xiaoyan Tang, Renqiang Liu, Dan Pan, Xijun Wang, Jinying Ge, Zhiyuan Wen, Zhigao Bu
收稿日期: 2021-02-23 录用日期: 2021-08-04 出版日期: 2021-10-08
云南省景洪市登革热患者恢复期不同阶段血清流行病学调查
马樱硕, 李曼, 谢吕, 高娜, 范东瀛, 冯恺豪, 姚瑶, 周勇, 盛子洋, 周红宁, 陈辉, 安静
收稿日期: 2021-04-29 录用日期: 2021-08-28 出版日期: 2021-09-29

登革热患者恢复期血清抗体的衰减变化规律与感染风险及预后密切相关。机体感染登革病毒(dengue virus, DENV)后,体内的中和抗体随时间的推移逐渐下降至亚中和浓度时,极易因抗体依赖性增强效应(antibody dependent enhancement, ADE)促进重症登革的发生。本队列研究收集了云南省景洪市2013年登革热患者恢复期不同阶段的血清样本,探究DENV特异性抗体的动态变化规律,分析再次感染异血清型DENV发生ADE的风险。我们于2017年和2019年分别采集191份四年恢复期及99份六年恢复期血清样本。四年恢复期血清DENV特异性IgG阳性率为98.4%,而六年恢复期血清IgG阳性率下降至82.8%;同时中和抗体几何平均效价由1:155.35下降至1:46.66。在290个总体样本中,73名连续追踪患者同时参加了2017年和2019年回访。在连续追踪样本中,四年恢复期血清针对DENV-3中和抗体以及DENV-1、DENV-2和DENV-4交叉反应性抗体几何平均效价分别为1:167.70、1:13.80、1:18.54和1:45.26;两年后,其效价分别下降至1:53.18、1:10.30、1:14.60和1:8.17。在ADE风险分析中,随着恢复期延长,31-40岁和51-60岁年龄组连续追踪患者在2019年样本中针对DENV-4的ADE阳性人数增加,导致再次感染DENV-4发生ADE的风险增加,而再次感染DENV-1和DENV-2发生ADE的风险降低。本研究对登革高发区域重症登革的风险预测以及登革疫苗的相关研究提供了重要实验依据。

After dengue virus (DENV) infection, antibody-dependent enhancement (ADE) is easy to occur when the neutralizing antibody (NAb) gradually decreases to a sub-neutralizing concentration. In this cohort surveillance, we utilized sera samples collected from dengue fever patients at different convalescent phases in Jinghong City, to investigate the dynamic change rule of DENV-specific antibodies, and to analyze the risk of ADE caused by secondary infection with heterologous serotypes DENVs. For baseline serosurvey, 191 four-year and 99 six-year sera samples during convalescence were collected in 2017 and 2019, respectively. The positive rate of DENV-specific immunoglobulin G was 98.4% in 2017, which significantly decreased to 82.8% in 2019. The geometric mean titer (GMT) of NAb decreased from 1:155.35 to 1:46.66. Among 290 overall samples, 73 paired consecutive samples were used for follow-up serosurvey. In four-year sera, the GMTs of NAb against DENV3 and cross-reactive antibodies against DENV-1, DENV-2 and DENV-4 were 1:167.70, 1:13.80, 1:18.54 and 1:45.26, respectively, which decreased to 1:53.18, 1:10.30, 1:14.60 and 1:8.17 in six-year sera. In age-stratified analysis, due to the increasing number of ADE positive samples from 2017 to 2019 in 31–40 and 51–60 years groups, the risk of ADE in DENV-4 infection was positively associated with the extension of convalescent phase, and the odd ratio was higher than other groups. With the recovery period lengthened, the risk of secondary infection with DENV-1 and DENV-2 was reduced. Our results offer essential experimental data for risk prediction of severe dengue in hyper-endemic dengue areas, and provide crucial scientific insight for the development of effective dengue vaccines.

Japanese Encephalitis Virus NS2B-3 Protein Complex Promotes Cell Apoptosis and Viral Particle Release by Down-Regulating the Expression of AXL
Shengda Xie, Zhenjie Liang, Xingmiao Yang, Junhui Pan, Du Yu, Tongtong Li, Ruibing Cao
doi: 10.1007/s12250-021-00442-3
收稿日期: 2021-05-14 录用日期: 2021-07-12 出版日期: 2021-09-06
Characterization of Episomal Replication of Bovine Papillomavirus Type 1 DNA in Long-Term Virion-Infected Saccharomyces Cerevisiae Culture
Quanmei Tu, Weixu Feng, Zhuo Chen, Qijia Li, Yu Zhao, Jun Chen, Pengfei Jiang, Xiangyang Xue, Lifang Zhang, Kong-Nan Zhao
doi: 10.1007/s12250-021-00439-y
收稿日期: 2021-02-22 录用日期: 2021-05-21 出版日期: 2021-08-30
Three Novel Avastroviruses Identified in Dead Wild Crows
Chunge Zhang, Yongchun Yang, Tao Hu, Hong Zhou, Cheng Zhang, Jian Cao, Juan Li, Peihan Wang, Gary Wong, Xiaodu Wang, Houhui Song, George F. Gao, Weifeng Shi, Yuhai Bi
doi: 10.1007/s12250-021-00416-5
收稿日期: 2021-02-22 录用日期: 2021-04-27 出版日期: 2021-08-30
The Establishment and Spatiotemporal History of A Novel HIV-1 CRF01_AE Lineage in Shenyang City, Northeastern China in 2002–2019
Minghui An, Wei Song, Bin Zhao, Xue Dong, Lin Wang, Wen Tian, Xin Li, Lu Wang, Zhenxing Chu, Junjue Xu, Haibo Ding, Xiaoxu Han, Hong Shang
doi: 10.1007/s12250-021-00435-2
收稿日期: 2021-05-24 录用日期: 2021-06-28 出版日期: 2021-08-23
Generation and Characterization of a Nanobody Against SARS-CoV
Jiang-Fan Li, Lei He, Yong-Qiang Deng, Shu-Hui Qi, Yue-Hong Chen, Xiao-Lu Zhang, Shi-Xiong Hu, Rui-Wen Fan, Guang-Yu Zhao, Cheng-Feng Qin
doi: 10.1007/s12250-021-00436-1
收稿日期: 2021-03-28 录用日期: 2021-05-06 出版日期: 2021-08-17
Structure and Function of N-Terminal Zinc Finger Domain of SARS-CoV-2 NSP2
Jun Ma, Yiyun Chen, Wei Wu, Zhongzhou Chen
doi: 10.1007/s12250-021-00431-6
收稿日期: 2021-06-14 录用日期: 2021-07-15 出版日期: 2021-08-16
A multi-center study on Molecular Epidemiology of Human Respiratory Syncytial Virus from Children with Acute Lower Respiratory Tract Infections in the Mainland of China between 2015 and 2019
Xiangpeng Chen, Yun Zhu, Wei Wang, Changchong Li, Shuhua An, Gen Lu, Rong Jin, Baoping Xu, Yunlian Zhou, Aihuan Chen, Lei Li, Meng Zhang, Zhengde Xie
doi: 10.1007/s12250-021-00430-7
收稿日期: 2021-01-29 录用日期: 2021-05-18 出版日期: 2021-08-16
SARS-CoV-2 Genomic Sequencing Revealed N501Y and L452R Mutants of S/A Lineage in Tianjin Municipality, China
Xiaoyan Li, Xin Gao, Ming Zou, Zhichao Zhuang, Zhaolin Tan, Baolu Zheng, Aiping Yu, Xu Su
doi: 10.1007/s12250-021-00432-5
收稿日期: 2021-03-31 录用日期: 2021-05-26 出版日期: 2021-08-11
In Vitro Inhibition of Alphaviruses by Lycorine
Na Li, Zhen Wang, Rui Wang, Zhe-Rui Zhang, Ya-Nan Zhang, Cheng-Lin Deng, Bo Zhang, Lu-Qing Shang, Han-Qing Ye
doi: 10.1007/s12250-021-00438-z
收稿日期: 2021-05-08 录用日期: 2021-06-08 出版日期: 2021-08-10
Inhibition of the Neddylation Pathway Suppresses Enterovirus Replication
Zhe Zhang, Haoran Guo, Jing Wang, Yan Li, Yanhang Gao, Quan Liu, Junqi Niu, Wei Wei
doi: 10.1007/s12250-021-00427-2
收稿日期: 2021-02-04 录用日期: 2021-05-26 出版日期: 2021-08-05
Genomic Characterization of a New Coronavirus from Migratory Birds in Jiangxi Province of China
Wentao Zhu, Wentao Song, Guoyin Fan, Jing Yang, Shan Lu, Dong Jin, Xue-lian Luo, Ji Pu, Haiying Chen, Jianguo Xu
doi: 10.1007/s12250-021-00402-x
收稿日期: 2021-01-25 录用日期: 2021-03-29 出版日期: 2021-07-08
Consecutive Monitoring of Interleukin-6 Is Needed for COVID-19 Patients
Xiaohua Chen, Juan Zhou, Chen Chen, Baidong Hou Hou, Ashaq Ali, Feng Li, Zhaolin Hua, Yingtao Wu, Qin Yang, Min Chen, Rong Zhang, Qianchuan Huang, Jinya Ding, Xian-En Zhang, Dong Men
doi: 10.1007/s12250-021-00425-4
收稿日期: 2021-01-26 录用日期: 2021-05-21 出版日期: 2021-07-07
Two Inhibitors Against the 3C-Like Proteases of Swine Coronavirus and Feline Coronavirus
Mengxin Zhou, Yutong Han, Mengxia Li, Gang Ye, Guiqing Peng
doi: 10.1007/s12250-021-00415-6
收稿日期: 2021-02-19 录用日期: 2021-05-06 出版日期: 2021-07-06
Non-Structural Protein 5 of Zika Virus Interacts with p53 in Human Neural Progenitor Cells and Induces p53-Mediated Apoptosis
Ping Li, Hualian Jiang, Hong Peng, Weijie Zeng, Yongheng Zhong, Miao He, Luyang Xie, Junhai Chen, Deyin Guo, Junyu Wu, Chun-Mei Li
doi: 10.1007/s12250-021-00422-7
收稿日期: 2021-04-05 录用日期: 2021-06-08 出版日期: 2021-07-05
Desmoglein 2 (DSG2) Is A Receptor of Human Adenovirus Type 55 Causing Adult Severe Community-Acquired Pneumonia
Jing Zhang, Kui Ma, Xiangyu Wang, Yinbo Jiang, Shan Zhao, Junxian Ou, Wendong Lan, Wenyi Guan, Xiaowei Wu, Heping Zheng, Bin Yang, Chengsong Wan, Wei Zhao, Jianguo Wu, Qiwei Zhang
doi: 10.1007/s12250-021-00414-7
收稿日期: 2021-02-12 录用日期: 2021-05-06 出版日期: 2021-07-05
Antibody Cocktail Exhibits Broad Neutralization Activity Against SARS-CoV-2 and SARS-CoV-2 Variants
Yuanyuan Qu, Xueyan Zhang, Meiyu Wang, Lina Sun, Yongzhong Jiang, Cheng Li, Wei Wu, Zhen Chen, Qiangling Yin, Xiaolin Jiang, Yang Liu, Chuan Li, Jiandong Li, Tianlei Ying, Dexin Li, Faxian Zhan, Youchun Wang, Wuxiang Guan, Shiwen Wang, Mifang Liang
doi: 10.1007/s12250-021-00409-4
收稿日期: 2021-03-16 录用日期: 2021-05-06 出版日期: 2021-07-05
CRISPR/Cas12a Technology Combined with RT-ERA for Rapid and Portable SARS-CoV-2 Detection
Sihua Liu, Mengqian Huang, Yanan Xu, Jun Kang, Sheng Ye, Si Liu, Zhiyun Wang, Hongyun Liu, Jibin Yu, Kongxin Hu, Tao Wang
doi: 10.1007/s12250-021-00406-7
收稿日期: 2020-11-24 录用日期: 2021-03-28 出版日期: 2021-07-02
ANXA2 Facilitates Enterovirus 71 Infection by Interacting with 3D Polymerase and PI4KB to Assist the Assembly of Replication Organelles
Qiuhan Zhang, Siliang Li, Ping Lei, Zixian Li, Feifei Chen, Qi Chen, Yulu Wang, Jiami Gong, Qi Tang, Xinjin Liu, Ke Lan, Shuwen Wu
doi: 10.1007/s12250-021-00417-4
收稿日期: 2021-03-14 录用日期: 2021-04-27 出版日期: 2021-07-01
Profiles of SARS-CoV-2 RNA and Antibodies in Inpatients with COVID-19 not Related with Clinical Manifestation: A Single Centre Study
Li Zhao, Ruqin Gao, Roujian Lu, Huijuan Wang, Yao Deng, Peihua Niu, Fachun Jiang, Baoying Huang, Jiwei Liang, Jing Jia, Feng Zhang, Wenling Wang, Guizhen Wu, Wenjie Tan
doi: 10.1007/s12250-021-00411-w
收稿日期: 2020-08-13 录用日期: 2021-04-30 出版日期: 2021-07-01
Recovery of a Far-Eastern Strain of Tick-Borne Encephalitis Virus with a Full-Length Infectious cDNA Clone
Penghui Li, Chen Yao, Ting Wang, Tong Wu, Wenfu Yi, Yue Zheng, Yuanjiu Miao, Jianhong Sun, Zhongyuan Tan, Yan Liu, Xiaowei Zhang, Hanzhong Wang, Zhenhua Zheng
doi: 10.1007/s12250-021-00396-6
收稿日期: 2020-07-17 录用日期: 2021-03-15 出版日期: 2021-06-30
New Simian Enterovirus 19 (EV-A122) Strains in China Reveal Large-Scale Inter-Serotype Recombination between Simian EV-As
Zhenzhi Han, Jinbo Xiao, Yang Song, Shuangli Zhu, Dongyan Wang, Huanhuan Lu, Tianjiao Ji, Dongmei Yan, Wenbo Xu, Yong Zhang
doi: 10.1007/s12250-021-00412-9
收稿日期: 2020-12-06 录用日期: 2021-04-13 出版日期: 2021-06-29
Ectopic Expression of TRIM25 Restores RIG-I Expression and IFN Production Reduced by Multiple Enteroviruses 3Cpro
Huimin Xiao, Jingliang Li, Xu Yang, Zhaolong Li, Ying Wang, Yajuan Rui, Bin Liu, Wenyan Zhang
doi: 10.1007/s12250-021-00410-x
收稿日期: 2021-01-31 录用日期: 2021-04-12 出版日期: 2021-06-25
Clinical Characteristics of Human Adenovirus Plastic Bronchitis in 10 Pediatric Cases: A Retrospective Study of Seven Years
Lingjian Zeng, Jianhua Wei, Yuyi Tang, Enmei Liu, Qubei Li, Na Zang
doi: 10.1007/s12250-021-00394-8
收稿日期: 2020-11-02 录用日期: 2021-04-25 出版日期: 2021-06-22
Histone Deacetylase Inhibitor SAHA Induces Expression of Fatty Acid-Binding Protein 4 and Inhibits Replication of Human Cytomegalovirus
Zhongshun Liu, Baoqin Xuan, Shubing Tang, Zhikang Qian
doi: 10.1007/s12250-021-00382-y
收稿日期: 2020-07-10 录用日期: 2021-03-11 出版日期: 2021-06-22
Current Status of Human Papillomavirus-Related Head and Neck Cancer: From Viral Genome to Patient Care
Haoru Dong, Xinhua Shu, Qiang Xu, Chen Zhu, Andreas M. Kaufmann, Zhi-Ming Zheng, Andreas E. Albers, Xu Qian
doi: 10.1007/s12250-021-00413-8
收稿日期: 2021-01-21 录用日期: 2021-05-18 出版日期: 2021-06-21
The Application of a Safe Neutralization Assay for Ebola Virus Using Lentivirus-Based Pseudotyped Virus
Zengguo Cao, Hongli Jin, Gary Wong, Ying Zhang, Cuicui Jiao, Na Feng, Fangfang Wu, Shengnan Xu, Hang Chi, Yongkun Zhao, Tiecheng Wang, Weiyang Sun, Yuwei Gao, Songtao Yang, Xianzhu Xia, Hualei Wang
doi: 10.1007/s12250-021-00405-8
收稿日期: 2020-07-28 录用日期: 2021-04-19 出版日期: 2021-06-21
Dynamic Host Immune and Transcriptomic Responses to Respiratory Syncytial Virus Infection in a Vaccination-Challenge Mouse Model
Yu Zhao, Chen Ma, Jie Yang, Xiufen Zou, Zishu Pan
doi: 10.1007/s12250-021-00418-3
收稿日期: 2021-04-08 录用日期: 2021-04-20 出版日期: 2021-06-17
The C/EBPb-Dependent Induction of TFDP2 Facilitates Porcine Reproductive and Respiratory Syndrome Virus Proliferation
Min Zhu, Xiaoyang Li, Ruiqi Sun, Peidian Shi, Aiping Cao, Lilin Zhang, Yanyu Guo, Jinhai Huang
doi: 10.1007/s12250-021-00403-w
收稿日期: 2021-02-07 录用日期: 2021-04-28 出版日期: 2021-06-17
Antigenic Drift of the Hemagglutinin from an Influenza A (H1N1) pdm09 Clinical Isolate Increases its Pathogenicity In Vitro
Lei Xing, Yunbo Chen, Boqian Chen, Ling Bu, Ying Liu, Zhiqi Zeng, Wenda Guan, Qigao Chen, Yongping Lin, Kun Qin, Honglin Chen, Xilong Deng, Xinhua Wang, Wenjun Song
doi: 10.1007/s12250-021-00401-y
收稿日期: 2021-01-06 录用日期: 2021-04-12 出版日期: 2021-06-09
Development and Characterization of SYBR Green Ⅰ Based RT-PCR Assay for Detection of Omsk Hemorrhagic Fever Virus
Ya-Nan Zhang, Si-Qing Liu, Cheng-Lin Deng, Zhi-Ming Yuan, Bo Zhang, Xiao-Dan Li, Han-Qing Ye
doi: 10.1007/s12250-021-00389-5
收稿日期: 2021-01-10 录用日期: 2021-03-17 出版日期: 2021-06-02
Safety and Considerations of the COVID-19 Vaccine Massive Deployment
Junwei Li, Mingyue Song, Deyin Guo, Yongxiang Yi
doi: 10.1007/10.1007/s12250-021-00408-5
收稿日期: 2021-02-20 录用日期: 2021-04-26 出版日期: 2021-06-01
Cholesterol-25-Hydroxylase Suppresses Seneca Valley Virus Infection via Producing 25-Hydroxycholesterol to Block Adsorption Procedure
Hui Li, Zekai Zhao, Xiangmin Li, Liuxing Qin, Wei Wen, Huanchun Chen, Ping Qian
doi: 10.1007/s12250-021-00377-9
收稿日期: 2020-06-03 录用日期: 2020-09-22 出版日期: 2021-06-01
Modulation of Antiviral Immunity and Therapeutic Efficacy by 25-Hydroxycholesterol in Chronically SIV-Infected, ART-Treated Rhesus Macaques
Chunxiu Wu, Jin Zhao, Ruiting Li, Fengling Feng, Yizi He, Yanjun Li, Runhan Huang, Guangye Li, Heng Yang, Genhong Cheng, Ling Chen, Feng Ma, Pingchao Li, Caijun Sun
doi: 10.1007/s12250-021-00407-6
收稿日期: 2021-01-29 录用日期: 2021-04-19 出版日期: 2021-05-31
The Functional Characterization of Bat and Human P[3] Rotavirus VP8*s
Dandi Li, Mengxuan Wang, Tongyao Mao, Mingwen Wang, Qing Zhang, Hong Wang, Lili Pang, Xiaoman Sun, Zhaojun Duan
doi: 10.1007/s12250-021-00400-z
收稿日期: 2021-01-06 录用日期: 2021-04-12 出版日期: 2021-05-31
Re-isolation of Wuxiang Virus from Wild Sandflies Collected from Yangquan County, China
Qinyan Wang, Shihong Fu, Jingxia Cheng, Xiuyan Xu, Jing Wang, Bin Wu, Xiaodong Tian, Yan Li, Ying He, Fan Li, Kai Nie, Songtao Xu, Bin Wang, Huanyu Wang, Xiaoqing Lu, Guodong Liang
doi: 10.1007/s12250-021-00398-4
收稿日期: 2020-11-17 录用日期: 2021-03-25 出版日期: 2021-05-31
Computational Viromics: Applications of the Computational Biology in Viromics Studies
Congyu Lu, Yousong Peng
doi: 10.1007/s12250-021-00395-7
收稿日期: 2020-06-02 录用日期: 2021-04-14 出版日期: 2021-05-31
PML Suppresses Influenza Virus Replication by Promoting FBXW7 Expression
Hai-Yan Yan, Hui-Qiang Wang, Ming Zhong, Shuo Wu, Lu Yang, Ke Li, Yu-Huan Li
doi: 10.1007/s12250-021-00399-3
收稿日期: 2020-12-16 录用日期: 2021-03-29 出版日期: 2021-05-27
Cucurbit[7]uril as a Broad-Spectrum Antiviral Agent against Diverse RNA Viruses
Jia Quan, Xiangjun Zhang, Yuanfu Ding, Shengke Li, Yang Qiu, Ruibing Wang, Xi Zhou
doi: 10.1007/s12250-021-00404-9
收稿日期: 2021-03-25 录用日期: 2021-04-06 出版日期: 2021-05-26
Anti-SARS-CoV-2 IgY Isolated from Egg Yolks of Hens Immunized with Inactivated SARS-CoV-2 for Immunoprophylaxis of COVID-19
Haiyan Shen, Yanxing Cai, Huan Zhang, Jie Wu, Lin Ye, Penghui Yang, Xiaojun Lin, Shibo Jiang, Ming Liao
doi: 10.1007/s12250-021-00371-1
收稿日期: 2020-11-29 录用日期: 2021-02-08 出版日期: 2021-05-21
Epidemiological Characteristics of Influenza A and B in Macau, 2010–2018
HoiMan Ng, Teng Zhang, Guoliang Wang, SiMeng Kan, Guoyi Ma, Zhe Li, Chang Chen, Dandan Wang, MengIn Wong, ChioHang Wong, Jinliang Ni, Xiaohua Douglas Zhang
doi: 10.1007/s12250-021-00388-6
收稿日期: 2020-12-04 录用日期: 2021-03-04 出版日期: 2021-05-20
Transcriptome Analyses Implicate Endogenous Retroviruses Involved in the Host Antiviral Immune System through the Interferon Pathway
Miao Wang, Liying Wang, Haizhou Liu, Jianjun Chen, Di Liu
doi: 10.1007/s12250-021-00370-2
收稿日期: 2020-10-10 录用日期: 2021-02-08 出版日期: 2021-05-19
A Convenient and Biosafe Replicon with Accessory Genes of SARS-CoV-2 and Its Potential Application in Antiviral Drug Discovery
Yun-Yun Jin, Hanwen Lin, Liu Cao, Wei-Chen Wu, Yanxi Ji, Liubing Du, Yiling Jiang, Yanchun Xie, Kuijie Tong, Fan Xing, Fuxiang Zheng, Mang Shi, Ji-An Pan, Xiaoxue Peng, Deyin Guo
doi: 10.1007/s12250-021-00385-9
收稿日期: 2021-03-02 录用日期: 2021-03-11 出版日期: 2021-05-17
Enriched Opportunistic Pathogens Revealed by Metagenomic Sequencing Hint Potential Linkages between Pharyngeal Microbiota and COVID-19
Dongyan Xiong, Caroline Muema, Xiaoxu Zhang, Xinming Pan, Jin Xiong, Hang Yang, Junping Yu, Hongping Wei
doi: 10.1007/s12250-021-00391-x
收稿日期: 2020-12-15 录用日期: 2021-03-15 出版日期: 2021-05-12
Accelerated Evolution of H7N9 Subtype Influenza Virus under Vaccination Pressure
Yifan Wu, Jingkai Hu, Xuanjiang Jin, Xiao Li, Jinfeng Wang, Mengmeng Zhang, Jianglin Chen, Shumin Xie, Wenbao Qi, Ming Liao, Weixin Jia
doi: 10.1007/s12250-021-00383-x
收稿日期: 2020-10-21 录用日期: 2021-03-17 出版日期: 2021-05-11
Expansion of GARP-Expressing CD4+CD25-FoxP3+ T Cells and SATB1 Association with Activation and Coagulation in Immune Compromised HIV-1-Infected Individuals in South Africa
Eman Teer, Danzil E. Joseph, Leanne Dominick, Richard H. Glashoff, M. Faadiel Essop
doi: 10.1007/s12250-021-00386-8
收稿日期: 2020-09-17 录用日期: 2021-02-23 出版日期: 2021-05-11
Development of RNA Polymerase III-Driven Reverse Genetics System for the Rescue of a Plant Rhabdovirus
Xiaoyan Zhang, Kai Sun, Yan Liang, Chenglu Zhao, Zhenghe Li
doi: 10.1007/s12250-021-00390-y
收稿日期: 2020-11-23 录用日期: 2021-03-25 出版日期: 2021-05-03
Detection of SARS-CoV-2 RNA in Medical Wastewater in Wuhan During the COVID-19 Outbreak
Jun-Bo Zhou, Wen-Hua Kong, Sheng Wang, Yi-Bing Long, Lian-Hua Dong, Zhen-Yu He, Man-Qing Liu
doi: 10.1007/s12250-021-00373-z
收稿日期: 2020-07-28 录用日期: 2021-01-14 出版日期: 2021-05-03
Porcine Bocavirus: A 10-Year History since Its Discovery
Manita Aryal, Guangliang Liu
doi: 10.1007/s12250-021-00365-z
收稿日期: 2020-07-04 录用日期: 2020-12-11 出版日期: 2021-04-28
A Virulent PEDV Strain FJzz1 with Genomic Mutations and Deletions at the High Passage Level Was Attenuated in Piglets via Serial Passage In Vitro
Pengfei Chen, Xiongwei Zhao, Shuting Zhou, Tianxing Zhou, Xiangmei Tan, Xia Wu, Wu Tong, Fei Gao, Lingxue Yu, Yifeng Jiang, Hai Yu, Zhibiao Yang, Guangzhi Tong, Yanjun Zhou
doi: 10.1007/s12250-021-00368-w
收稿日期: 2020-09-28 录用日期: 2020-12-28 出版日期: 2021-04-28
Human Endogenous Retroviruses as Biomedicine Markers
Yuhe Song, Xiang Li, Xiaoman Wei, Jie Cui
doi: 10.1007/s12250-021-00387-7
收稿日期: 2020-08-22 录用日期: 2021-03-15 出版日期: 2021-04-27
Genetic Mutation of SARS-CoV-2 during Consecutive Passages in Permissive Cells
Ying Chen, Mei-Qin Liu, Yun Luo, Ren-Di Jiang, Hao-Rui Si, Yan Zhu, Bei Li, Xu-Rui Shen, Hao-Feng Lin, Kai Zhao, Ben Hu, Zheng-Li Shi, Xing-Lou Yang
doi: 10.1007/s12250-021-00384-w
收稿日期: 2020-12-08 录用日期: 2021-03-15 出版日期: 2021-04-26
Beagle Dogs Have Low Susceptibility to Florida Clade 2 H3N8 Equine Avian Influenza
Pei Zhou, Xiangyu Xiao, Xinkai Hu, Jie Dong, Haoyao Zhang, Yanchao Li, Shoujun Li
doi: 10.1007/s12250-021-00366-y
收稿日期: 2020-08-03 录用日期: 2021-01-25 出版日期: 2021-04-15
Rapid Acquisition of High-Quality SARS-CoV-2 Genome via AmpliconOxford Nanopore Sequencing
Yi Yan, Ke Wu, Jun Chen, Haizhou Liu, Yi Huang, Yong Zhang, Jin Xiong, Weipeng Quan, Xin Wu, Yu Liang, Kunlun He, Zhilong Jia, Depeng Wang, Di Liu, Hongping Wei, Jianjun Chen
doi: 10.1007/s12250-021-00378-8
收稿日期: 2020-10-28 录用日期: 2021-02-18 出版日期: 2021-04-13
Recombinant GII.4[P31] Was Predominant Norovirus Circulating in Beijing Area, China, 2018–2020
Junhong Ai, Meng Zhang, Fang Jin, Zhengde Xie
doi: 10.1007/s12250-021-00381-z
收稿日期: 2020-11-28 录用日期: 2021-02-20 出版日期: 2021-04-09
Protective Efficacy of Inactivated Vaccine against SARS-CoV-2 Infection in Mice and Non-Human Primates
Yan-Feng Yao, Ze-Jun Wang, Ren-Di Jiang, Xue Hu, Hua-Jun Zhang, Yi-Wu Zhou, Ge Gao, Ying Chen, Yun Peng, Mei-Qin Liu, Ya-Nan Zhang, Juan Min, Jia Lu, Xiao-Xiao Gao, Jing Guo, Cheng Peng, Xu-Rui Shen, Qian Li, Kai Zhao, Lian Yang, Xin Wan, Bo Zhang, Wen-Hui Wang, Jia Wu, Peng Zhou, Xing-Lou Yang, Shuo Shen, Chao Shan, Zhi-Ming Yuan, Zheng-Li Shi
doi: 10.1007/s12250-021-00376-w
收稿日期: 2021-01-23 录用日期: 2021-02-08 出版日期: 2021-04-09
Construction of Non-infectious SARS-CoV-2 Replicons and Their Application in Drug Evaluation
Bei Wang, Chongyang Zhang, Xiaobo Lei, Lili Ren, He Huang, Jianwei Wang, Zhendong Zhao
doi: 10.1007/s12250-021-00369-9
收稿日期: 2020-12-07 录用日期: 2021-02-09 出版日期: 2021-04-09
3H-31, A Non-structural Protein of Heliothis virescens ascovirus 3h, Inhibits the Host Larval Cathepsin and Chitinase Activities
Huan Yu, Yi-Yi Ou-Yang, Chang-Jin Yang, Ni Li, Madoka Nakai, Guo-Hua Huang
doi: 10.1007/s12250-021-00374-y
收稿日期: 2020-08-29 录用日期: 2020-11-16 出版日期: 2021-04-08
Host Interferon-Stimulated Gene 20 Inhibits Pseudorabies Virus Proliferation
Xiaoyong Chen, Dage Sun, Sujie Dong, Huanjie Zhai, Ning Kong, Hao Zheng, Wu Tong, Guoxin Li, Tongling Shan, Guangzhi Tong
doi: 10.1007/s12250-021-00380-0
收稿日期: 2020-10-29 录用日期: 2021-02-23 出版日期: 2021-04-08
Stability of SARS-CoV-2 on the Surfaces of Three Meats in the Setting That Simulates the Cold Chain Transportation
Xiao-Li Feng, Bei Li, Hao-Feng Lin, Hong-Yi Zheng, Ren-Rong Tian, Rong-Hua Luo, Mei-Qin Liu, Ren-Di Jiang, Yong-Tang Zheng, Zheng-Li Shi, Yu-Hai Bi, Xing-Lou Yang
doi: 10.1007/s12250-021-00367-x
收稿日期: 2020-10-09 录用日期: 2021-02-01 出版日期: 2021-04-08
Ozone Water Is an Effective Disinfectant for SARS-CoV-2
Xiao Hu, Zhen Chen, Zhengyuan Su, Fei Deng, Xinwen Chen, Qi Yang, Pan Li, Quanjiao Chen, Jun Ma, Wuxiang Guan, Rongjuan Pei, Yun Wang
doi: 10.1007/s12250-021-00379-7
收稿日期: 2021-01-13 录用日期: 2021-02-23 出版日期: 2021-03-31
Human Endogenous Retrovirus Type W Envelope from Multiple Sclerosis Demyelinating Lesions Shows Unique Solubility and Antigenic Characteristics
Benjamin Charvet, Justine Pierquin, Joanna Brunel, Rianne Gorter, Christophe Quétard, Branka Horvat, Sandra Amor, Jacques Portoukalian, Hervé Perron
doi: 10.1007/s12250-021-00372-0
收稿日期: 2021-02-02 录用日期: 2021-02-08 出版日期: 2021-03-26
Role of Intracellular Distribution of Feline and Bovine SAMHD1 Proteins in Lentiviral Restriction
Chu Wang, Lina Meng, Jialin Wang, Kaikai Zhang, Sizhu Duan, Pengyu Ren, Yingzhe Wei, Xinyu Fu, Bin Yu, Jiaxin Wu, Xianghui Yu
doi: 10.1007/s12250-021-00351-5
收稿日期: 2020-08-03 录用日期: 2020-12-28 出版日期: 2021-03-22
Significant Inhibition of Porcine Epidemic Diarrhea Virus In Vitro by Remdesivir, Its Parent Nucleoside and β-D-N4-hydroxycytidine
Yuanchao Xie, Xiaozhen Guo, Tianwen Hu, Daibao Wei, Xiuli Ma, Jiaqiang Wu, Bing Huang, Jingshan Shen
doi: 10.1007/s12250-021-00362-2
收稿日期: 2020-10-15 录用日期: 2021-01-22 出版日期: 2021-03-22
Porcine Picornavirus 3C Protease Degrades PRDX6 to Impair PRDX6-mediated Antiviral Function
Congcong Wang, Huanhuan Feng, Xiangle Zhang, Kangli Li, Fan Yang, Weijun Cao, Huisheng Liu, Lili Gao, Zhaoning Xue, Xiangtao Liu, Zixiang Zhu, Haixue Zheng
doi: 10.1007/s12250-021-00352-4
收稿日期: 2020-09-30 录用日期: 2020-12-17 出版日期: 2021-03-15
Peroxiredoxin-6 (PRDX6) is an antioxidant enzyme with both the activities of peroxidase and phospholipase A2 (PLA2), which is involved in regulation of many cellular reactions. However, the function of PRDX6 during virus infection remains unknown. In this study, we found that the abundance of PRDX6 protein was dramatically decreased in foot-and-mouth disease virus (FMDV) infected cells. Overexpression of PRDX6 inhibited FMDV replication. In contrast, knockdown of PRDX6 expression promoted FMDV replication, suggesting an antiviral role of PRDX6. To explore whether the activity of peroxidase and PLA2 was associated with PRDX6-mediated antiviral function, a specific inhibitor of PLA2 (MJ33) and a specific inhibitor of peroxidase activity (mercaptosuccinate) were used to treat the cells before FMDV infection. The results showed that incubation of MJ33 but not mercaptosuccinate promoted FMDV replication. Meanwhile, overexpression of PRDX6 slightly enhanced type I interferon signaling. We further determined that the viral 3Cpro was responsible for degradation of PRDX6, and 3Cpro-induced reduction of PRDX6 was independent of the proteasome, lysosome, and caspase pathways. The protease activity of 3Cpro was required for induction of PRDX6 reduction. Besides, PRDX6 suppressed the replication of another porcine picornavirus Senecavirus A (SVA), and the 3Cpro of SVA induced the reduction of PRDX6 through its proteolytic activity as well. Together, our results suggested that PRDX6 plays an important antiviral role during porcine picornavirus infection, and the viral 3Cpro induces the degradation of PRDX6 to overcome PRDX6-mediated antiviral function.Peroxiredoxin-6 (PRDX6) is an antioxidant enzyme with both the activities of peroxidase and phospholipase A2 (PLA2), which is involved in regulation of many cellular reactions. However, the function of PRDX6 during virus infection remains unknown. In this study, we found that the abundance of PRDX6 protein was dramatically decreased in foot-and-mouth disease virus (FMDV) infected cells. Overexpression of PRDX6 inhibited FMDV replication. In contrast, knockdown of PRDX6 expression promoted FMDV replication, suggesting an antiviral role of PRDX6. To explore whether the activity of peroxidase and PLA2 was associated with PRDX6-mediated antiviral function, a specific inhibitor of PLA2 (MJ33) and a specific inhibitor of peroxidase activity (mercaptosuccinate) were used to treat the cells before FMDV infection. The results showed that incubation of MJ33 but not mercaptosuccinate promoted FMDV replication. Meanwhile, overexpression of PRDX6 slightly enhanced type I interferon signaling. We further determined that the viral 3Cpro was responsible for degradation of PRDX6, and 3Cpro-induced reduction of PRDX6 was independent of the proteasome, lysosome, and caspase pathways. The protease activity of 3Cpro was required for induction of PRDX6 reduction. Besides, PRDX6 suppressed the replication of another porcine picornavirus Senecavirus A (SVA), and the 3Cpro of SVA induced the reduction of PRDX6 through its proteolytic activity as well. Together, our results suggested that PRDX6 plays an important antiviral role during porcine picornavirus infection, and the viral 3Cpro induces the degradation of PRDX6 to overcome PRDX6-mediated antiviral function.
Autographa Californica Multiple Nucleopolyhedrovirus orf13 Is Required for Efficient Nuclear Egress of Nucleocapsids
Xingang Chen, Xiaoqin Yang, Chengfeng Lei, Fujun Qin, Xiulian Sun, Jia Hu
doi: 10.1007/s12250-021-00353-3
收稿日期: 2020-10-20 录用日期: 2020-12-18 出版日期: 2021-03-15
Autographa californica multiple nucleopolyhedrovirus (AcMNPV) orf13 (ac13) is a conserved gene in all sequenced alphabaculoviruses. However, its function in the viral life cycle remains unknown. In this study, we found that ac13 was a late gene and that the encoded protein, bearing a putative nuclear localization signal motif, colocalized with the nuclear lamina. Deletion of ac13 did not affect viral genome replication, nucleocapsid assembly or occlusion body (OB) formation, but reduced virion budding from infected cells by approximately 400-fold compared with the wild-type virus. Deletion of ac13 substantially impaired the egress of nucleocapsids from the nucleus to the cytoplasm, while the OB morphogenesis was unaffected. Taken together, our results indicated that ac13 was required for efficient nuclear egress of nucleocapsids during virion budding, but was dispensable for OB formation.Autographa californica multiple nucleopolyhedrovirus (AcMNPV) orf13 (ac13) is a conserved gene in all sequenced alphabaculoviruses. However, its function in the viral life cycle remains unknown. In this study, we found that ac13 was a late gene and that the encoded protein, bearing a putative nuclear localization signal motif, colocalized with the nuclear lamina. Deletion of ac13 did not affect viral genome replication, nucleocapsid assembly or occlusion body (OB) formation, but reduced virion budding from infected cells by approximately 400-fold compared with the wild-type virus. Deletion of ac13 substantially impaired the egress of nucleocapsids from the nucleus to the cytoplasm, while the OB morphogenesis was unaffected. Taken together, our results indicated that ac13 was required for efficient nuclear egress of nucleocapsids during virion budding, but was dispensable for OB formation.
Porcine Coronaviruses: Overview of the State of the Art
Hanna Turlewicz-Podbielska, Małgorzata Pomorska-Mól
doi: 10.1007/s12250-021-00364-0
收稿日期: 2020-05-26 录用日期: 2020-11-19 出版日期: 2021-03-15
Like RNA viruses in general, coronaviruses (CoV) exhibit high mutation rates which, in combination with their strong tendency to recombine, enable them to overcome the host species barrier and adapt to new hosts. It is currently known that six CoV are able to infect pigs. Four of them belong to the genus Alphacoronavirus [transmissible gastroenteritis coronavirus (TEGV), porcine respiratory coronavirus (PRCV), porcine epidemic diarrhea virus (PEDV), swine acute diarrhea syndrome coronavirus (SADS-CoV)], one of them to the genus Betacoronavirus [porcine hemagglutinating encephalomyelitis virus (PHEV)] and the last one to the genus Deltacoronavirus (PDCoV). PHEV was one of the first identified swine CoV and is still widespread, causing subclinical infections in pigs in several countries. PRCV, a spike deletion mutant of TGEV associated with respiratory tract infection, appeared in the 1980s. PRCV is considered non-pathogenic since its infection course is mild or subclinical. Since its appearance, pig populations have become immune to both PRCV and TGEV, leading to a significant reduction in the clinical and economic importance of TGEV. TGEV, PEDV and PDCoV are enteropathogenic CoV and cause clinically indistinguishable acute gastroenteritis in all age groups of pigs. PDCoV and SADS-CoV have emerged in 2014 (US) and in 2017 (China), respectively. Rapid diagnosis is crucial for controlling CoV infections and preventing them from spreading. Since vaccines are available only for some porcine CoV, prevention should focus mainly on a high level of biosecurity. In view of the diversity of CoV and the potential risk factors associated with zoonotic emergence, updating the knowledge concerning this area is essential.Like RNA viruses in general, coronaviruses (CoV) exhibit high mutation rates which, in combination with their strong tendency to recombine, enable them to overcome the host species barrier and adapt to new hosts. It is currently known that six CoV are able to infect pigs. Four of them belong to the genus Alphacoronavirus [transmissible gastroenteritis coronavirus (TEGV), porcine respiratory coronavirus (PRCV), porcine epidemic diarrhea virus (PEDV), swine acute diarrhea syndrome coronavirus (SADS-CoV)], one of them to the genus Betacoronavirus [porcine hemagglutinating encephalomyelitis virus (PHEV)] and the last one to the genus Deltacoronavirus (PDCoV). PHEV was one of the first identified swine CoV and is still widespread, causing subclinical infections in pigs in several countries. PRCV, a spike deletion mutant of TGEV associated with respiratory tract infection, appeared in the 1980s. PRCV is considered non-pathogenic since its infection course is mild or subclinical. Since its appearance, pig populations have become immune to both PRCV and TGEV, leading to a significant reduction in the clinical and economic importance of TGEV. TGEV, PEDV and PDCoV are enteropathogenic CoV and cause clinically indistinguishable acute gastroenteritis in all age groups of pigs. PDCoV and SADS-CoV have emerged in 2014 (US) and in 2017 (China), respectively. Rapid diagnosis is crucial for controlling CoV infections and preventing them from spreading. Since vaccines are available only for some porcine CoV, prevention should focus mainly on a high level of biosecurity. In view of the diversity of CoV and the potential risk factors associated with zoonotic emergence, updating the knowledge concerning this area is essential.
Establishment of a Reverse Genetic System of Severe Fever with Thrombocytopenia Syndrome Virus Based on a C4 Strain
Mingyue Xu, Bo Wang, Fei Deng, Hualin Wang, Manli Wang, Zhihong Hu, Jia Liu
doi: 10.1007/s12250-021-00359-x
收稿日期: 2020-12-18 录用日期: 2021-01-21 出版日期: 2021-03-15
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes hemorrhagic fever-like disease (SFTS) in humans with a case fatality rate up to 30%. To date, the molecular biology involved in SFTSV infection remains obscure. There are seven major genotypes of SFTSV (C1–C4 and J1–J3) and previously a reverse genetic system was established on a C3 strain of SFTSV. Here, we reported successfully establishment of a reverse genetics system based on a SFTSV C4 strain. First, we obtained the 5′- and 3′-terminal untranslated region (UTR) sequences of the Large (L), Medium (M) and Small (S) segments of a laboratory-adapted SFTSV C4 strain through rapid amplification of cDNA ends analysis, and developed functional T7 polymerase-based L-, M- and S-segment minigenome assays. Then, full-length cDNA clones were constructed and infectious SFTSV were recovered from co-transfected cells. Viral infectivity, growth kinetics, and viral protein expression profile of the rescued virus were compared with the laboratory-adapted virus. Focus formation assay showed that the size and morphology of the foci formed by the rescued SFTSV were indistinguishable with the laboratory-adapted virus. However, one-step growth curve and nucleoprotein expression analyses revealed the rescued virus replicated less efficiently than the laboratory-adapted virus. Sequence analysis indicated that the difference may be due to the mutations in the laboratory-adapted strain which are more prone to cell culture. The results help us to understand the molecular biology of SFTSV, and provide a useful tool for developing vaccines and antivirals against SFTS.Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes hemorrhagic fever-like disease (SFTS) in humans with a case fatality rate up to 30%. To date, the molecular biology involved in SFTSV infection remains obscure. There are seven major genotypes of SFTSV (C1–C4 and J1–J3) and previously a reverse genetic system was established on a C3 strain of SFTSV. Here, we reported successfully establishment of a reverse genetics system based on a SFTSV C4 strain. First, we obtained the 5′- and 3′-terminal untranslated region (UTR) sequences of the Large (L), Medium (M) and Small (S) segments of a laboratory-adapted SFTSV C4 strain through rapid amplification of cDNA ends analysis, and developed functional T7 polymerase-based L-, M- and S-segment minigenome assays. Then, full-length cDNA clones were constructed and infectious SFTSV were recovered from co-transfected cells. Viral infectivity, growth kinetics, and viral protein expression profile of the rescued virus were compared with the laboratory-adapted virus. Focus formation assay showed that the size and morphology of the foci formed by the rescued SFTSV were indistinguishable with the laboratory-adapted virus. However, one-step growth curve and nucleoprotein expression analyses revealed the rescued virus replicated less efficiently than the laboratory-adapted virus. Sequence analysis indicated that the difference may be due to the mutations in the laboratory-adapted strain which are more prone to cell culture. The results help us to understand the molecular biology of SFTSV, and provide a useful tool for developing vaccines and antivirals against SFTS.
Sustainability of SARS-CoV-2 Induced Humoral Immune Responses in COVID-19 Patients from Hospitalization to Convalescence Over Six Months
Yang Zheng, Qing Zhang, Ashaq Ali, Ke Li, Nan Shao, Xiaoli Zhou, Zhiqin Ye, Xiaomin Chen, Shanshan Cao, Jing Cui, Juan Zhou, Dianbing Wang, Baidong Hou, Min Li, Mengmeng Cui, Lihua Deng, Xinyi Sun, Qian Zhang, Qinfang Yang, Yong li, Hui Wang, Yake Lei, Bo Yu, Yegang Cheng, Xiaolin Tong, Dong Men, Xian-En Zhang
doi: 10.1007/s12250-021-00360-4
收稿日期: 2020-11-24 录用日期: 2021-01-13 出版日期: 2021-03-04
Understanding the persistence of antibody in convalescent COVID-19 patients may help to answer the current major concerns such as the risk of reinfection, the protection period of vaccination and the possibility of building an active herd immunity. This retrospective cohort study included 172 COVID-19 patients who were hospitalized in Wuhan. A total of 404 serum samples were obtained over six months from hospitalization to convalescence. Antibodies in the specimens were quantitatively analyzed by the capture chemiluminescence immunoassays (CLIA). All patients were positive for the anti-SARS-CoV-2 IgM/IgG at the onset of COVID-19 symptoms, and the IgG antibody persisted in all the patients during the convalescence. However, only approximately 25% of patients can detect the IgM antibodies, IgM against N protein (N-IgM) and receptor binding domain of S protein (RBD-IgM) at the 27th week. The titers of IgM, N-IgM and RBD-IgM reduced to 16.7%, 17.6% and 15.2% of their peak values respectively. In contrast, the titers of IgG, N-IgG and RBD-IgG peaked at 4–5th week and reduced to 85.9%, 62.6% and 87.2% of their peak values respectively at the end of observation. Dynamic behavior of antibodies and their correlation in age, gender and severity groups were investigated. In general, the COVID-19 antibody was sustained at high levels for over six months in most of the convalescent patients. Only a few patients with antibody reducing to an undetectable level which needs further attention. The humoral immune response against SARS-CoV-2 infection in COVID-19 patients exhibits a typical dynamic of acquired immunity.Understanding the persistence of antibody in convalescent COVID-19 patients may help to answer the current major concerns such as the risk of reinfection, the protection period of vaccination and the possibility of building an active herd immunity. This retrospective cohort study included 172 COVID-19 patients who were hospitalized in Wuhan. A total of 404 serum samples were obtained over six months from hospitalization to convalescence. Antibodies in the specimens were quantitatively analyzed by the capture chemiluminescence immunoassays (CLIA). All patients were positive for the anti-SARS-CoV-2 IgM/IgG at the onset of COVID-19 symptoms, and the IgG antibody persisted in all the patients during the convalescence. However, only approximately 25% of patients can detect the IgM antibodies, IgM against N protein (N-IgM) and receptor binding domain of S protein (RBD-IgM) at the 27th week. The titers of IgM, N-IgM and RBD-IgM reduced to 16.7%, 17.6% and 15.2% of their peak values respectively. In contrast, the titers of IgG, N-IgG and RBD-IgG peaked at 4–5th week and reduced to 85.9%, 62.6% and 87.2% of their peak values respectively at the end of observation. Dynamic behavior of antibodies and their correlation in age, gender and severity groups were investigated. In general, the COVID-19 antibody was sustained at high levels for over six months in most of the convalescent patients. Only a few patients with antibody reducing to an undetectable level which needs further attention. The humoral immune response against SARS-CoV-2 infection in COVID-19 patients exhibits a typical dynamic of acquired immunity.
Alterations in Phenotypes and Responses of T Cells Within 6 Months of Recovery from COVID-19: A Cohort Study
Bali Zhao, Maohua Zhong, Qingyu Yang, Ke Hong, Jianbo Xia, Xia Li, Ying Liu, Yao-Qing Chen, Jingyi Yang, Chaolin Huang, Huimin Yan
doi: 10.1007/s12250-021-00348-0
收稿日期: 2020-10-11 录用日期: 2020-11-30 出版日期: 2021-02-09
The COVID-19 pandemic, caused by the SARS-CoV-2 infection, is a global health crisis. While many patients have clinically recovered, little is known about long-term alterations in T cell responses of COVID-19 convalescents. In this study, T cell responses in peripheral blood mononuclear cells of a long-time COVID-19 clinically recovered (20–26 weeks) cohort (LCR) were measured via flow cytometry and ELISpot. The T cell responses of LCR were comparatively analyzed against an age and sex matched short-time clinically recovered (4–9 weeks) cohort (SCR) and a healthy donor cohort (HD). All volunteers were recruited from Wuhan Jinyintan Hospital, China. Phenotypic analysis showed that activation marker PD-1 expressing on CD4+ T cells of LCR was still significantly lower than that of HD. Functional analysis indicated that frequencies of Tc2, Th2 and Th17 in LCR were comparable to those of HD, but Tc17 was higher than that of HD. In LCR, compared to the HD, there were fewer IFN-γ producing T cells but more IL-2 secreting T cells. In addition, the circulating Tfh cells in LCR were still slightly lower compared to HD, though the subsets composition had recovered. Remarkably, SARS-CoV-2 specific T cell responses in LCR were comparable to that of SCR. Collectively, T cell responses experienced long-term alterations in phenotype and functional potential of LCR cohort. However, after clinical recovery, SARS-CoV-2 specific T cell responses could be sustained at least for six months, which may be helpful in resisting re-infection.The COVID-19 pandemic, caused by the SARS-CoV-2 infection, is a global health crisis. While many patients have clinically recovered, little is known about long-term alterations in T cell responses of COVID-19 convalescents. In this study, T cell responses in peripheral blood mononuclear cells of a long-time COVID-19 clinically recovered (20–26 weeks) cohort (LCR) were measured via flow cytometry and ELISpot. The T cell responses of LCR were comparatively analyzed against an age and sex matched short-time clinically recovered (4–9 weeks) cohort (SCR) and a healthy donor cohort (HD). All volunteers were recruited from Wuhan Jinyintan Hospital, China. Phenotypic analysis showed that activation marker PD-1 expressing on CD4+ T cells of LCR was still significantly lower than that of HD. Functional analysis indicated that frequencies of Tc2, Th2 and Th17 in LCR were comparable to those of HD, but Tc17 was higher than that of HD. In LCR, compared to the HD, there were fewer IFN-γ producing T cells but more IL-2 secreting T cells. In addition, the circulating Tfh cells in LCR were still slightly lower compared to HD, though the subsets composition had recovered. Remarkably, SARS-CoV-2 specific T cell responses in LCR were comparable to that of SCR. Collectively, T cell responses experienced long-term alterations in phenotype and functional potential of LCR cohort. However, after clinical recovery, SARS-CoV-2 specific T cell responses could be sustained at least for six months, which may be helpful in resisting re-infection.
36卷第4期 (2021年8月)

ISSN 1674-0769

EISSN 1995-820X

CN 42-1760/Q

主编: 石正丽

影响因子: 4.327*

*源于2020年JCR

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