2022 Vol.37(4)

Apis mellifera filamentous virus (AmFV) is a large DNA virus that is endemic in honeybee colonies, which belongs to the class Naldaviricetes but not the order Lefavirales. The genome sequence of the AmFV Swiss isolate has been reported but so far very few molecular studies have been conducted.
In this issue, Yang et al. isolated and purified AmFV virions from honeybee colonies in China, conducted next-generation genomic sequencing and compared it to that of the Swiss strain. A total of 197 ORFs were identified, among which 36 putative genes including 18 homologs were annotated. Further proteomic analysis identified 47 virion-associated proteins, of which 14 are putative major structural proteins. Their study provides fundamental information for future molecular studies on AmFV.
The cover is adopted from an electron micrograph of Apis mellifera filamentous virus (AmFV CN) from Chinese honeybee with unique morphology (kindly provided by Prof. Zhihong Hu), with artistic processing. The long neucleocapsid forms three figure-eight loops and is wrapped in the ovoid virions. See page 483–490 for details.


Monkeypox virus: a re-emergent threat to humans

Qizan Gong, Changle Wang, Xia Chuai, Sandra Chiu

2022, 37(4): 477 doi: 10.1016/j.virs.2022.07.006

Received: 07 June 2022 Accepted: 05 July 2022
Abstract [PDF 1132 KB] ScienceDirect
Human monkeypox (MPX) is a rare zoonotic infection characterized by smallpox-like signs and symptoms. It is caused by monkeypox virus (MPXV), a double stranded DNA virus belonging to the genus Orthopoxvirus. MPX was first identified in 1970 and mostly prevailed in the rural rainforests of Central and West Africa in the past. Outside Africa, MPX was reported in the United Kingdom, the USA, Israel, and Singapore. In 2022, the resurgence of MPX in Europe and elsewhere posed a potential threat to humans. MPXV was transmitted by the animals-human or human-human pathway, and the symptoms of MPXV infection are similar to that of smallpox, but in a milder form and with lower mortality (1%–10%). Although the smallpox vaccination has been shown to provide 85% protection against MPXV infection, and two anti-smallpox virus drugs have been approved to treat MPXV, there are still no specific vaccines and drugs against MPXV infection. Therefore it is urgent to take active measures including the adoption of novel anti-MPXV strategies to control the spread of MPXV and prevent MPX epidemic. In this review, we summarize the biological features, epidemiology, pathogenicity, laboratory diagnosis, and prevention and treatment strategies on MPXV. This review provides the basic knowledge for prevention and control of future outbreaks of this emerging infection.
Research Article

Genomics and proteomics of Apis mellifera filamentous virus isolated from honeybees in China

Dahe Yang, Jun Wang, Xi Wang, Fei Deng, Qingyun Diao, Manli Wang, Zhihong Hu, Chunsheng Hou

2022, 37(4): 483 doi: 10.1016/j.virs.2022.02.007

Received: 22 October 2021 Accepted: 21 February 2022
Abstract [PDF 835 KB] ScienceDirect
Apis mellifera filamentous virus (AmFV) is a large DNA virus that is endemic in honeybee colonies. The genome sequence of the AmFV Swiss isolate (AmFV CH–C05) has been reported, but so far very few molecular studies have been conducted on this virus. In this study, we isolated and purified AmFV (AmFV CN) from Chinese honeybee (Apis mellifera) colonies and elucidated its genomics and proteomics. Electron microscopy showed ovoid purified virions with dimensions of 300–500×210–285 nm, wrapping a 3165×40 nm filamentous nucleocapsid in three figure-eight loops. Unlike AmFV CH–C05, which was reported to have a circular genome, our data suggest that AmFV CN has a linear genome of approximately 493 kb. A total of 197 ORFs were identified, among which 36 putative genes including 18 baculoviral homologs were annotated. The overall nucleotide similarity between the CN and CH–C05 isolates was 96.9%. Several ORFs were newly annotated in AmFV CN, including homologs of per os infectivity factor 4 (PIF4) and a putative integrase. Phylogenomic analysis placed AmFVs on a separate branch within the newly proposed virus class Naldaviricetes. Proteomic analysis revealed 47 AmFV virion-associated proteins, of which 14 had over 50% sequence coverage, suggesting that they are likely to be main structural proteins. In addition, all six of the annotated PIFs (PIF-0–5) were identified by proteomics, suggesting that they may function as entry factors in AmFV infection. This study provides fundamental information regarding the molecular biology of AmFV.

Discovery of novel DNA viruses in small mammals from Kenya

Griphin Ochieng Ochola, Bei Li, Vincent Obanda, Sheila Ommeh, Harold Ochieng, Xing-Lou Yang, Samson Omondi Onyuok, Zheng-Li Shi, Bernard Agwanda, Ben Hu

2022, 37(4): 491 doi: 10.1016/j.virs.2022.06.001

Received: 18 November 2021 Accepted: 17 May 2022
Abstract [PDF 3603 KB] ScienceDirectESM
Emergence and re-emergence of infectious diseases of wildlife origin have led pre-emptive pathogen surveillances in animals to be a public health priority. Rodents and shrews are among the most numerically abundant vertebrate taxa and are known as natural hosts of important zoonotic viruses. Many surveillance programs focused more on RNA viruses. In comparison, much less is known about DNA viruses harbored by these small mammals. To fill this knowledge gap, tissue specimens of 232 animals including 226 rodents, five shrews and one hedgehog were collected from 5 counties in Kenya and tested for the presence of DNA viruses belonging to 7 viral families by PCR. Diverse DNA sequences of adenoviruses, adeno-associated viruses, herpesviruses and polyomaviruses were detected. Phylogenetic analyses revealed that most of these viruses showed distinction from previously described viruses and formed new clusters. Furthermore, this is the first report of the discovery and full-length genome characterization of a polyomavirus in Lemniscomys species. This novel polyomavirus, named LsPyV KY187, has less than 60% amino acid sequence identity to the most related Glis glis polyomavirus 1 and Sciurus carolinensis polyomavirus 1 in both large and small T-antigen proteins and thus can be putatively allocated to a novel species within Betapolyomavirus. Our findings help us better understand the genetic diversity of DNA viruses in rodent and shrew populations in Kenya and provide new insights into the evolution of those DNA viruses in their small mammal reservoirs. It demonstrates the necessity of ongoing pathogen discovery studies targeting rodent-borne viruses in East Africa.

Genotype distribution and evolutionary analysis of rotavirus associated with acute diarrhea outpatients in Hubei, China, 2013–2016

Ting Zhang, Jing Li, Yong-Zhong Jiang, Jun-Qiang Xu, Xu-Hua Guan, Li-Qiang Wang, Jie Chen, Yi Liang

2022, 37(4): 503 doi: 10.1016/j.virs.2022.05.005

Received: 26 March 2021 Accepted: 17 May 2022
Abstract [PDF 5347 KB] ScienceDirect ESM
Group A human rotaviruses (RVAs) annually cause the deaths of 215,000 infants and young children. To understand the epidemiological characteristics and genetic evolution of RVAs, we performed sentinel surveillance on RVA prevalence in a rotavirus-surveillance network in Hubei, China. From 2013 to 2016, a total of 2007 fecal samples from hospital outpatients with acute gastroenteritis were collected from four cities of Hubei Province. Of the 2007 samples, 153 (7.62%) were identified positive for RVA by real-time RT-PCR. RVA infection in Hubei mainly occurred in autumn and winter. The highest detection rate of RVA infection was in 1–2 years old of outpatients (16.97%). No significant difference of RVA positive rate was observed between females and males. We performed a phylogenetic analysis of the G/P genotypes based on the partial VP7/VP4 gene sequences of RVAs. G9P[8] was the most predominant strain in all four years but the prevalence of G2P[4] genotype increased rapidly since 2014. We reconstructed the evolutionary time scale of RVAs in Hubei, and found that the evolutionary rates of the G9, G2, P[8], and P[4] genotypes of RVA were 1.069×10-3, 1.029×10-3, 1.283×10-3 and 1.172×10-3 nucleotide substitutions/site/year, respectively. Importantly, using a molecular clock model, we showed that most G9, G2, P[8], and P[4] genotype strains dated from the recent ancestor in 2005, 2005, 1993, and 2013, respectively. The finding of the distribution of RVAs in infants and young children in Hubei Province will contribute to the understanding of the epidemiological characteristics and genetic evolution of RVAs in China.

A serologic investigation of epizootic hemorrhagic disease virus in China between 2014 and 2019

Yingliang Duan, Zhenxing Yang, Pei Zhu, Lei Xiao, Zhanhong Li, Zhuoran Li, Le Li, Jianbo Zhu

2022, 37(4): 513 doi: 10.1016/j.virs.2022.06.005

Received: 10 December 2021 Accepted: 13 June 2022
Abstract [PDF 1677 KB] ScienceDirectESM
Epizootic hemorrhagic disease virus (EHDV) is a member of the genus Orbivirus, family Sedoreoviridae. It was firstly recognized in 1955 to cause a highly fatal disease of wild white-tailed deer in America. So far, EHDV was detected and isolated in many wild or domestic ruminants, and widely distributed all over the world. Although the domestic cattle and sheep infected by EHDV were usually asymptomatic or subclinical, several outbreaks of epizootic hemorrhagic disease (EHD) in deer and cattle had been reported. Many EHDV strains were isolated and sequenced in last two decades in China, which promoted a general serologic investigation of EHDV in China. In this study, 18,122 sera were collected from asymptomatic or subclinical domestic ruminants (cattle, cow, yaks, sheep, goats, and deer) in 116 regions belonging to 15 provinces in China. All the sera were tested by EHDV C-ELISA, and the results were obtained by big data analysis. EHDV infections were detected in the 14 of 15 provinces, and only Tibet (average altitude ≥ 4000 m) which was the highest province in China was free of EHDV. The numbers of seropositive collections in both bovine and goat/sheep were in an inverse proportion to the latitude. However, the seropositive rates in bovine were ranged from 0% to 100%, while the seropositive rates in goat/sheep were no more than 50%. The results suggested that bovine was obviously more susceptive for EHDV infection than goat and sheep, therefore might be a major reservoir of EHDV in China. The prevalence of EHDV was consistent with the distribution of Culicoides which were known as the sole insect vectors of EHDV. In particular, the seropositive rates of EHDV were very high in the southern provinces, which required the enhanced surveillance in the future.

ISG20 inhibits bluetongue virus replication

Di Kang, Shandian Gao, Zhancheng Tian, Guorui Zhang, Guiquan Guan, Guangyuan Liu, Jianxun Luo, Junzheng Du, Hong Yin

2022, 37(4): 521 doi: 10.1016/j.virs.2022.04.010

Received: 29 August 2021 Accepted: 22 April 2022
Abstract [PDF 2419 KB] ScienceDirectESM
ISG20 is an interferon-inducible exonuclease that inhibits virus replication. Although ISG20 is thought to degrade viral RNA, the antiviral mechanism and specificity of ISG20 remain unclear. In this study, the antiviral role of ovine ISG20 (oISG20) in bluetongue virus (BTV) infection was investigated. It was found that BTV infection upregulated the transcription of ovine ISG20 (oISG20) in a time- and BTV multiplicity of infection (MOI)-dependent manner. Overexpression of oISG20 suppressed the production of BTV genome, proteins, and virus titer, whereas the knockdown of oISG20 increased viral replication. oISG20 was found to co-localize with BTV proteins VP4, VP5, VP6, and NS2, but only directly interacted with VP4. Exonuclease defective oISG20 significantly decreased the inhibitory effect on BTV replication. In addition, the interaction of mutant oISG20 and VP4 was weakened, suggesting that binding to VP4 was associated with the inhibition of BTV replication. The present data characterized the anti-BTV effect of oISG20, and provides a novel clue for further exploring the inhibition mechanism of double-stranded RNA virus by ISG20.

Screening and identification of HTNVpv entry inhibitors with high-throughput pseudovirus-based chemiluminescence

Xiaojing Wen, Li Zhang, Qiang Liu, Xinyue Xiao, Weijin Huang, Youchun Wang

2022, 37(4): 531 doi: 10.1016/j.virs.2022.04.015

Received: 12 March 2021 Accepted: 03 September 2021
Abstract [PDF 832 KB] ScienceDirect
Hantaviruses, such as Hantaan virus (HTNV) and Seoul virus, are the causative agents of Hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS), and are important zoonotic pathogens. China has the highest incidence of HFRS, which is mainly caused by HTNV and Seoul virus. No approved antiviral drugs are available for these hantaviral diseases. Here, a chemiluminescence-based high-throughput-screening (HTS) assay was developed and used to screen HTNV pseudovirus (HTNVpv) inhibitors in a library of 1813 approved drugs and 556 small-molecule compounds from traditional Chinese medicine sources. We identified six compounds with in vitro anti-HTNVpv activities in the low-micromolar range (EC50 values of 0.1–2.2 μmol/L; selectivity index of 40–900). Among the six selected compounds, cepharanthine not only showed good anti-HTNVpv activity in vitro but also inhibited HTNVpv-fluc infection in Balb/c mice 5 h after infection by 94% (180 mg/kg/d, P < 0.01), 93% (90 mg/kg/d, P < 0.01), or 92% (45 mg/kg/d, P < 0.01), respectively, in a bioluminescent imaging mouse model. A time-of-addition analysis suggested that the antiviral mechanism of cepharanthine involves the membrane fusion and entry phases. Overall, we have established a HTS method for antiviral drugs screening, and shown that cepharanthine is a candidate for HCPS and HFRS therapy. These findings may offer a starting point for the treatment of patients infected with hantaviruses.

Identification of a phage-derived depolymerase specific for KL47 capsule of Klebsiella pneumoniae and its therapeutic potential in mice

Min Li, Hui Wang, Long Chen, Genglin Guo, Pei Li, Jiale Ma, Rong Chen, Hong Du, Yuqing Liu, Wei Zhang

2022, 37(4): 538 doi: 10.1016/j.virs.2022.04.005

Received: 14 October 2021 Accepted: 28 April 2022
Abstract [PDF 1938 KB] ScienceDirectESM
Klebsiella pneumoniae is one of the major pathogens causing global multidrug-resistant infections. Therefore, strategies for preventing and controlling the infections are urgently needed. Phage depolymerase, often found in the tail fiber protein or the tail spike protein, is reported to have antibiofilm activity. In this study, phage P560 isolated from sewage showed specific for capsule locus type KL47 K. pneumoniae, and the enlarged haloes around plaques indicated that P560 encoded a depolymerase. The capsule depolymerase, ORF43, named P560dep, derived from phage P560 was expressed, purified, characterized and evaluated for enzymatic activity as well as specificity. We reported that the capsule depolymerase P560dep, can digest the capsule polysaccharides on the surface of KL47 type K. pneumoniae, and the depolymerization spectrum of P560dep matched to the host range of phage P560, KL47 K. pneumoniae. Crystal violet staining assay showed that P560dep was able to significantly inhibit biofilm formation. Further, a single dose (50 μg/mouse) of depolymerase intraperitoneal injection protected 90%–100% of mice from lethal challenge before or after infection by KL47 carbapenem-resistant K. pneumoniae. And pathological changes were alleviated in lung and liver of mice infected by KL47 type K. pneumoniae. It is demonstrated that depolymerase P560dep as an attractive antivirulence agent represents a promising tool for antimicrobial therapy.

A microfluidic cell chip for virus isolation via rapid screening for permissive cells

Weide Su, Jingjiang Qiu, Ying Mei, Xian-En Zhang, Yong He, Feng Li

2022, 37(4): 547 doi: 10.1016/j.virs.2022.04.011

Received: 28 December 2021 Accepted: 11 April 2022
Abstract [PDF 5888 KB] ScienceDirectESM
Virus identification is a prerequisite not only for the early diagnosis of viral infectious diseases but also for the effective prevention of epidemics. Successful cultivation is the gold standard for identifying a virus, according to the Koch postulates. However, this requires screening for a permissive cell line, which is traditionally time-, reagent- and labor-intensive. Here, a simple and easy-to-operate microfluidic chip, formed by seeding a variety of cell lines and culturing them in parallel, is reported for use in virus cultivation and virus-permissive host-cell screening. The chip was tested by infection with two known viruses, enterovirus 71 (EV71) and influenza virus H1N1. Infection with EV71 and H1N1 caused significant cytopathic effects (CPE) in RD and MDCK cells, respectively, demonstrating that virus cultivation based on this microfluidic cell chip can be used as a substitute for the traditional plate-based culture method and reproduce the typical CPE caused by virus infection. Using this microfluidic cell chip method for virus cultivation could make it possible to identify an emerging virus in a high-throughput, automatic, and unprecedentedly fast way.

Establishment and characterization of a new cell culture system for hepatitis B virus replication and infection

Yingying Song, Shuyu Shou, Huimin Guo, Zixiang Gao, Nannan Liu, Yang Yang, Feifei Wang, Qiang Deng, Jing Liu, Youhua Xie

2022, 37(4): 558 doi: 10.1016/j.virs.2022.05.002

Received: 24 January 2022 Accepted: 18 April 2022
Abstract [PDF 2253 KB] ScienceDirectESM
Hepatitis B virus (HBV) is a primary cause of chronic liver diseases in humans. HBV infection exhibits strict host and tissue tropism. HBV core promoter (Cp) drives transcription of pregenomic RNA (pgRNA) and plays a key role in the viral life cycle. Hepatocyte nuclear factor 4α (HNF4α) acts as a major transcriptional factor that stimulates Cp. In this work, we reported that BEL7404 cell line displayed a high efficiency of DNA transfection and high levels of HBV antigen expression after transfection of HBV replicons without prominent viral replication. The introduction of exogenous HNF4α and human sodium taurocholate cotransporting polypeptide (hNTCP) expression into BEL7404 made it permissive for HBV replication and susceptible to HBV infection. BEL7404-derived cell lines with induced HBV permissiveness and susceptibility were constructed by stable co-transfection of hNTCP and Tet-inducible HNF4α followed by limiting dilution cloning. HBV replication in such cells was sensitive to inhibition by nucleotide analog tenofovir, while the infection was inhibited by HBV entry inhibitors. This cell culture system provides a new and additional tool for the study of HBV replication and infection as well as the characterization of antiviral agents.

STUB1 regulates antiviral RNAi through inducing ubiquitination and degradation of Dicer and AGO2 in mammals

Shumin Zhang, Xuhua Zhang, Yuanyuan Bie, Jing Kong, An Wang, Yang Qiu, Xi Zhou

2022, 37(4): 569 doi: 10.1016/j.virs.2022.05.001

Received: 01 March 2022 Accepted: 13 April 2022
Abstract [PDF 3117 KB] ScienceDirect
RNA interference (RNAi) is an intrinsic antiviral immune mechanism conserved in diverse eukaryotic organisms. However, the mechanism by which antiviral RNAi in mammals is regulated is poorly understood. In this study, we uncovered that the E3 ubiquitin ligase STIP1 homology and U-box-containing protein 1 (STUB1) was a new regulator of the RNAi machinery in mammals. We found that STUB1 interacted with and ubiquitinated AGO2, and targeted it for degradation in a chaperon-dependent manner. STUB1 promoted the formation of Lys48 (K48)-linked polyubiquitin chains on AGO2, and facilitated AGO2 degradation through ubiquitin-proteasome system. In addition to AGO2, STUB1 also induced the protein degradation of AGO1, AGO3 and AGO4. Further investigation revealed that STUB1 also regulated Dicer's ubiquitination via K48-linked polyubiquitin and induced the degradation of Dicer as well as its specialized form, termed antiviral Dicer (aviDicer) that expresses in mammalian stem cells. Moreover, we found that STUB1 deficiency up-regulated Dicer and AGO2, thereby enhancing the RNAi response and efficiently inhibiting viral replication in mammalian cells. Using the newborn mouse model of Enterovirus A71 (EV-A71), we confirmed that STUB1 deficiency enhanced the virus-derived siRNAs production and antiviral RNAi, which elicited a potent antiviral effect against EV-A71 infection in vivo. In summary, our findings uncovered that the E3 ubiquitin ligase STUB1 was a general regulator of the RNAi machinery by targeting Dicer, aviDicer and AGO1–4. Moreover, STUB1 regulated the RNAi response through mediating the abundance of Dicer and AGO2 during viral infection, thereby providing novel insights into the regulation of antiviral RNAi in mammals.

Recombinant chimpanzee adenovirus vector vaccine expressing the spike protein provides effective and lasting protection against SARS-CoV-2 infection in mice

Mingqing Lu, Kunpeng Liu, Yun Peng, Zhe Ding, Yingwen Li, Alexander Tendu, Xue Hu, Ge Gao, Weiwei Guo, Hang Liu, Juhong Rao, Jiaxuan Zhao, Miaoyu Chen, Zhiming Yuan, Gary Wong, Chao Shan, Yanfeng Yao, Jiaming Lan

2022, 37(4): 581 doi: 10.1016/j.virs.2022.05.006

Received: 14 December 2021 Accepted: 26 May 2022
Abstract [PDF 3731 KB] ScienceDirectESM
SARS-CoV-2 infection is a global public health threat. Vaccines are considered amongst the most important tools to control the SARS-CoV-2 pandemic. As expected, deaths from SARS-CoV-2 infection have dropped dramatically with widespread vaccination. However, there are concerns over the duration of vaccine-induced protection, as well as their effectiveness against emerging variants of concern. Here, we constructed a recombinant chimpanzee adenovirus vectored vaccine expressing the full-length spike of SARS-CoV-2 (AdC68-S). Rapid and high levels of humoral and cellular immune responses were observed after immunization of C57BL/6J mice with one or two doses of AdC68-S. Notably, neutralizing antibodies were observed up to at least six months after vaccination, without substantial decline. Single or double doses AdC68-S immunization resulted in lower viral loads in lungs of mice against SARS-CoV-2 challenge both in the short term (21 days) and long-term (6 months). Histopathological examination of AdC68-S immunized mice lungs showed mild histological abnormalities after SARS-CoV-2 infection. Taken together, this study demonstrates the efficacy and durability of the AdC68-S vaccine and constitutes a promising candidate for clinical evaluation.

Phospho-proteomics identifies a critical role of ATF2 in pseudorabies virus replication

Fang-Fang Jiang, Ren-Qi Wang, Chao-Yue Guo, Ke Zheng, Hai-Long Liu, Le Su, Sheng-Song Xie, Huan-Chun Chen, Zheng-Fei Liu

2022, 37(4): 591 doi: 10.1016/j.virs.2022.06.003

Received: 22 July 2021 Accepted: 02 June 2022
Abstract [PDF 2060 KB] ScienceDirect ESM
Pseudorabies virus (PRV), an etiological agent of pseudorabies in livestock, has negatively affected the porcine industry all over the world. Epithelial cells are reported as the first site of PRV infection. However, the role of host proteins and its related signaling pathways in PRV replication is largely unclear. In this study, we performed a quantitative phosphoproteomics screening on PRV-infected porcine kidney (PK-15) epithelial cells. Totally 5723 phosphopeptides, corresponding to 2180 proteins, were obtained, and the phosphorylated states of 810 proteins were significantly different in PRV-infected cells compared with mock-infected cells (P < 0.05). GO and KEGG analysis revealed that these differentially expressed phosphorylated proteins were predominantly related to RNA transport and MAPK signaling pathways. Further functional studies of NF-κB, transcription activator factor-2 (ATF2), MAX and SOS genes in MAPK signaling pathway were analyzed using RNA interference (RNAi) knockdown. It showed that only ATF2-knockdown reduces both PRV titer and viral genome copy number. JNK pathway inhibition and CRISPR/Cas9 gene knockout showed that ATF2 was required for the effective replication of PRV, especially during the biogenesis of viral genome DNA. Subsequently, by overexpression of the ATF2 gene and point mutation of the amino acid positions 69/71 of ATF2, it was further demonstrated that the phosphorylation of ATF2 promoted PRV replication. These findings suggest that ATF2 may provide potential therapeutic target for inhibiting PRV infection.

Growth hormone attenuates the brain damage caused by ZIKV infection in mice

Zi-Da Zhen, Na Wu, Dong-Ying Fan, Jun-Hong Ai, Zheng-Ran Song, Jia-Tong Chang, Pei-Gang Wang, Yan-Hua Wu, Jing An

2022, 37(4): 601 doi: 10.1016/j.virs.2022.06.004

Received: 15 January 2022 Accepted: 10 June 2022
Abstract [PDF 3708 KB] ScienceDirectESM
As a member of vector-borne viruses, Zika virus (ZIKV) can cause microcephaly and various neurological symptoms in newborns. Previously, we found that ZIKV could infect hypothalamus, causing a decrease in growth hormone (GH) secretion, growth delay and deficits in learning and memory in suckling mice. Early administration of GH can improve the cognitive function of the mice. Therefore, in this study we further investigated the mechanism underlying the protective role of GH in ZIKV infection in suckling mice. Our results showed that GH could effectively reduce brain damage caused by ZIKV infection via reducing cell apoptosis and inflammatory response rather than inhibiting viral replication. Our results provide important evidences not only for understanding the mechanism underlying ZIKV-associated neurological symptoms but also for the treatment of ZIKV infection.

Pathogenic analysis of coxsackievirus A10 in rhesus macaques

Suqin Duan, Fengmei Yang, Yanyan Li, Yuan Zhao, Li Shi, Meng Qin, Quan Liu, Weihua Jin, Junbin Wang, Lixiong Chen, Wei Zhang, Yongjie Li, Ying Zhang, Jingjing Zhang, Shaohui Ma, Zhanlong He, Qihan Li

2022, 37(4): 610 doi: 10.1016/j.virs.2022.06.007

Received: 17 August 2021 Accepted: 22 June 2022
Abstract [PDF 2824 KB] ScienceDirectESM
Coxsackievirus A10 (CV-A10) is one of the etiological agents associated with hand, foot and mouth disease (HFMD) and also causes a variety of illnesses in humans, including pneumonia, and myocarditis. Different people, particularly young children, may have different immunological responses to infection. Current CV-A10 infection animal models provide only a rudimentary understanding of the pathogenesis and effects of this virus. The characteristics of CV-A10 infection, replication, and shedding in humans remain unknown. In this study, rhesus macaques were infected by CV-A10 via respiratory or digestive route to mimic the HFMD in humans. The clinical symptoms, viral shedding, inflammatory response and pathologic changes were investigated in acute infection (1–11 day post infection) and recovery period (12–180 day post infection). All infected rhesus macaques during acute infection showed obvious viremia and clinical symptoms which were comparable to those observed in humans. Substantial inflammatory pathological damages were observed in multi-organs, including the lung, heart, liver, and kidney. During the acute period, all rhesus macaques displayed clinical signs, viral shedding, normalization of serum cytokines, and increased serum neutralizing antibodies, whereas inflammatory factors caused some animals to develop severe hyperglycemia during the recovery period. In addition, there were no significant differences between respiratory and digestive tract infected animals. Overall, all data presented suggest that the rhesus macaques provide the first non-human primate animal model for investigating CV-A10 pathophysiology and assessing the development of potential human therapies.

Development of functional antibodies against influenza B virus by activation-induced cytidine deaminase in hybridoma cells

Yuanzhi Chen, Chenguang Shen, Jing Chen, Junyu Chen, Fentian Chen, Limin Zhang, Xue Liu, Siyuan Chen, Sen Xue, Yongliang Liu, Jixian Tang, Quan Yuan, Yixin Chen, Wenxin Luo, Ningshao Xia

2022, 37(4): 619 doi: 10.1016/j.virs.2022.03.009

Received: 21 September 2021
Abstract [PDF 1515 KB] ScienceDirectESM
1. Class-switch recombination was mimicked in hybridomas through a controllable expression system of activation-induced cytidine deaminase.
2. IgG antibodies were generated through this system in an anti-Flu B IgM hybridoma 7G1.
3. IgG1 and IgG2a subtypes of 7G1 present improved antiviral activity in vitro and in vivo.

The outbreak of rabbit hemorrhagic virus type 2 in the interior of China may be related to imported semen

Ruibin Qi, Chunchun Meng, Jie Zhu, Hang Li, Qiuhong Miao, Jingyu Tang, Aoxing Tang, Hongyuan Guo, Chuncao Liu, Chuanfeng Li, Zongyan Chen, Fang Wang, Qinwen Zhang, Guangqing Liu

2022, 37(4): 623 doi: 10.1016/j.virs.2022.04.003

Received: 01 September 2021 Accepted: 01 April 2022
Abstract [PDF 1195 KB] ScienceDirectESM
1. We identified one RHD case caused by a new RHDV variant (GI.2) in China through HA, TEM, and genome sequencing.
2. This is the first study to demonstrate that GI.2 can replicate efficiently in the reproductive system.
3. Our evidence suggests that GI.2 might be introduced into China by contaminated rabbit semen.

Genetic characterization and pathogenicity of a reassortant Eurasian avian-like H1N1 swine influenza virus containing an internal gene cassette from 2009 pandemic H1N1 virus

Shuaiyong Wang, Manzhu Wang, Lingxue Yu, Juan Wang, Jiecong Yan, Xinli Rong, Yanjun Zhou, Tongling Shan, Wu Tong, Guoxin Li, Hao Zheng, Guangzhi Tong, Hai Yu

2022, 37(4): 627 doi: 10.1016/j.virs.2022.04.009

Received: 12 October 2021 Accepted: 11 April 2022
Abstract [PDF 2645 KB] ScienceDirectESM
1. Identification of a reassortant EA H1N1 SIV (SD/18) which isolated from a pig farm in Shandong, north China.
2. Phylogenetic analysis showed that SD/18 virus containing a complete internal gene cassette from pdm/09 virus.
3. The results of pathogenicity in mice showed that the mortality rate of SD/18 virus in mice could reach 100%.
4. The potential risk of EA lineage SIVs to humans is very high and we need to pay enough attention to the different reassortant EA H1N1 viruses.

Continued antigenic variation of highly pathogenic avian influenza A (H7N9) virus in laying hens in China, 2020–2021

Wenming Jiang, Xin Yin, Shuo Liu, Shaobo Liang, Cheng Peng, Guangyu Hou, Jinping Li, Xiaohui Yu, Yang Li, Jingjing Wang, Hualei Liu

2022, 37(4): 631 doi: 10.1016/j.virs.2022.04.012

Received: 14 December 2021 Accepted: 31 March 2022
Abstract [PDF 702 KB] ScienceDirectESM
1. 13 strains of H7N9 viruses from laying hens in 2020 and 2021 were identified.
2. H7N9 viruses in China comprised at least 11 genotypes.
3. H7N9 viruses are high pathogenic in chickens, not in ducks.
4. The most H7N9 viruses cross-reacted poorly with H7-Re3 antiserum.
5. The H7-Re3 vaccine was unable to prevent H7N9 infection.

The structure of Crimean-Congo hemorrhagic fever virus Gc is revealed; many more still need an answer

Wei Ye, Chuantao Ye, Yongliang Hu, Yangchao Dong, Yingfeng Lei, Fanglin Zhang

2022, 37(4): 634 doi: 10.1016/j.virs.2022.05.003

Received: 08 March 2022 Accepted: 07 May 2022
Abstract [PDF 747 KB] ScienceDirect
1. The structure of glycoprotein Gc, responsible for mediating membrane fusion between cell and CCHFV, is revealed, but many more mysteries remain.
2. Why do only antibodies against Gc have neutralizing effect, but not the one against Gn?
3. Why can NAbs against Gc only be protective in the animals in preventive settings, but not in the therapeutic administration?