寨卡病毒E蛋白编码序列上的单一非同义突变导致体内神经毒性显著增加
寨卡病毒可以感染包括人类胎儿发育性大脑在内的多种组织。特定的病毒基因变异是否与神经病理学有关尚不完全清楚。为了解决这一问题，我们在新生小鼠中连续传代了一株寨卡病毒临床分离株 (SW01)，发现连续传代可导致病毒毒性显著增加和神经向性的变异。深度测序分析结合分子病毒学研究表明，E蛋白上第67位氨基酸单一位点天冬氨酸（D）到天冬酰胺（N）的突变（D67N）足以显著增加病毒毒力和体内神经嗜性。值得注意的是，D67N突变的病毒克隆在体外的人神经星形胶质细胞U251细胞中具有更高的病毒产量，并引起更严重的细胞病变效应(CPE)，表明其对人脑具有潜在的神经毒性。这些发现表明，ZIKV包膜上的单一突变D67N可能导致严重的神经损伤，这可能有助于解释ZIKV的神经毒性，并提示在自然感染期间监测这种突变的发生可能很重要。
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IPEC-J2细胞感染PEDV强毒株和弱毒株后的转录组学分析
猪流行性腹泻病毒(Porcine epidemic diarrhea virus, PEDV)是引起猪腹泻、呕吐和死亡的主要原因，给全球养猪业造成了毁灭性的经济损失。近年来，随着RNA测序技术的发展，宿主感染PEDV后的晚期反应得以被研究；然而，目前尚没有针对宿主感染PEDV强毒株和弱毒株后早期反应的研究。因此，我们对猪肠道上皮细胞（IPEC-J2）感染PEDV强毒株(GDS01)或弱毒株(HX)3、6和12 h后的表达谱进行转录组学测序分析。结果显示，超过一半的差异表达基因在两个感染组中均表现出下调表达的模式。功能富集分析显示，GDS01组差异表达基因主要与自噬和凋亡通路相关，而HX组差异表达基因主要在免疫应答/炎症反应通路中富集。在差异表达基因中，TLR3和IFIT2基因与HX和GDS01毒株的增值速度有关，并通过TLR3抑制试验和IFIT2过表达试验在体外进行了验证。TLR3通过增强IFIT2的表达从而抑制了HX株的复制，而对GDS01株没有显著影响。综上，我们的研究揭示了PEDV强毒株和弱毒株感染早期基因表达模式和细胞过程/通路的异同，这些发现可能为控制PEDV的感染及新型治疗方法的研制奠定基础。
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克里米亚-刚果出血热病毒糖蛋白Gc的冷冻电镜结构
克里米亚-刚果出血热病毒(Crimean-Congo hemorrhagic fever virus, CCHFV)是一种引起人类严重出血性疾病的病原体，致死率高。CCHFV囊膜表面糖蛋白Gc在CCHFV入侵靶细胞过程中介导病毒与宿主膜融合，同时也是中和抗体的主要免疫靶标，因此其结构信息对于阐明病毒膜融合机制和研究中和抗体的中和机制至关重要，但到目前为止对CCHFV糖蛋白Gc的结构研究相对较少，尚无其胞外域蛋白结构的相关报道。
我们设计了Gc胞外域的三聚体蛋白，利用单颗粒分析技术解析了2.8 Å分辨率的Gc融合后结构，证实CCHFV糖蛋白Gc是II型膜融合蛋白。与布尼亚家族白纤病毒科和汉坦病毒科病毒已解析的Gc蛋白融合后结构进行结构、序列比较，发现CCHFV的Gc结构域III的排布方式与白纤病毒相似；但是其结构域II顶端的融合肽则与汉坦病毒的结构保守性较高。由于存在这种混合结构特征，我们推测在进化上CCHFV与这两种病毒均存在关联。Gc的结构解析，还帮助我们定位了Gc的抗原表位，因此提供了重要的结构信息以便分析各种抗体潜在的中和机制。
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我们设计了Gc胞外域的三聚体蛋白，利用单颗粒分析技术解析了2.8 Å分辨率的Gc融合后结构，证实CCHFV糖蛋白Gc是II型膜融合蛋白。与布尼亚家族白纤病毒科和汉坦病毒科病毒已解析的Gc蛋白融合后结构进行结构、序列比较，发现CCHFV的Gc结构域III的排布方式与白纤病毒相似；但是其结构域II顶端的融合肽则与汉坦病毒的结构保守性较高。由于存在这种混合结构特征，我们推测在进化上CCHFV与这两种病毒均存在关联。Gc的结构解析，还帮助我们定位了Gc的抗原表位，因此提供了重要的结构信息以便分析各种抗体潜在的中和机制。
高致病性H7N9禽流感病毒的裂解位点处碱性氨基酸和非碱性氨基酸的联合插入促进鸡和小鼠的致病性
自2016年中旬以来，低致病性H7N9流感病毒在我国演变为高致病性H7N9流感病毒，对家禽产业和公共卫生构成了极大的威胁。在高致病性H7N9流感病毒流行的早期，其裂解位点主要插入“KRTA”基序。随着H7N9流感病毒的传播，禽源和人源高致病性H7N9流感病毒的裂解位点更具有多态性，表现出碱性和非碱性氨基酸插入和氨基酸的替换，但这些插入和替换的潜在功能仍不清楚。在这里，我们通过反向遗传技术拯救出6株携带PEIPKGR/G、PEVPKGR/G、PEVPKRKRTAR/G、PEVPKGKRTAR/G、PEVPKGKRIAR/G和PEVPKRKRR/G基序的H7N9流感病毒。我们的研究结果表明，PEVPKRKRTAR/G基序的氨基酸插入在我国流行的高致病性H7N9病毒中占主导地位。有趣的是，删除H7N9病毒裂解位点的苏氨酸和丙氨酸后，H7N9病毒显著降低了热稳定性并且降低小鼠致病性。含有PEVPKRKRTAR/G基序的病毒在鸡上能够增强致病性，但是与其他高致病性H7N9病毒相比，其在鸡上的传播能力有所降低。以上结论解释了为何含有PEVPKRKRTAR/G基序的H7N9病毒在我国能够持续流行。与此相反，携带异亮氨酸和丙氨酸的H7N9病毒可降低鸡的传播率和小鼠的毒力。值得注意的是，H7N9病毒的HA蛋白的I335V氨基酸突变能够显著增强鸡的致病性和传播能力，表明H7N9的碱性氨基酸和非碱性氨基酸的联合插入以及裂解位点处I335V的替换促进了鸡和小鼠的复制能力和致病性。随着H7N9病毒的不断进化，其对家禽养殖业和人类健康的威胁越来越大，因此需要加强H7N9病毒的全面监测和预防。
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mTOR信号通路：连接细胞代谢和乙型肝炎病毒复制的桥梁
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哺乳动物雷帕霉素靶蛋白(mTOR)是一种保守的Ser/Thr激酶，包括mTOR复合物(mTORC) 1和mTORC2。mTOR通路在病毒性肝炎中被激活，包括HBV感染引起的肝炎。目前，慢性HBV感染仍然是世界范围内最严重的公共卫生问题之一。目前，HBV缺乏有效的治疗策略，迫切需要阐明HBV感染的发病机制。越来越多的证据表明，HBV感染可以激活mTOR信号通路，表明HBV可以利用或劫持mTOR信号通路以利于自身复制。因此，mTOR信号通路可能是控制HBV感染的关键目标。在本文中，我们总结并讨论了模型生物学研究中关于mTOR信号通路与HBV复制之间相互作用的最新发现。
人乳头瘤病毒相关头颈部肿瘤研究进展：从病毒基因组到临床实践
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近年来，对高危型人乳头瘤病毒（HPV）感染引起头颈部鳞癌发生和发展的研究不断地深入。据报道，约38%-80%的口咽部鳞癌以及大部分的宫颈癌都与HPV感染相关。病毒癌基因E6和E7的表达是致癌的关键。HPV阳性口咽部鳞癌表现出与阴性肿瘤不同的生物学行为和良好的预后。因此，为减少治疗带来的毒副作用和提高患者生存质量，一些临床研究开始探索降低HPV阳性口咽部鳞癌患者的治疗强度。但是，如何有效并且准确地筛选患者以接受不同强度的治疗仍然存在较大的挑战。与此同时，随着免疫治疗的不断临床应用，进一步理解HPV阳性肿瘤的免疫特性，深入研究患者对免疫治疗的不同反应，将有助于提高免疫治疗的疗效。本文就HPV相关头颈部鳞癌的生物学特性，以及目前对该类患者的临床研究进行综述。随着检测技术的不断进步，发现HPV相关头颈部鳞癌的特异性生物学标志物或治疗靶点将有助于临床对该类患者进行针对性的治疗。
生物矿化的新型腺病毒载体新冠肺炎疫苗对小鼠加强免疫的效果评价
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新型冠状病毒（SARS-CoV-2）感染已导致全球380多万人死亡。目前，有多种新型冠状病毒肺炎（COVID-19）疫苗获批准紧急使用，包括腺病毒载体疫苗，其热不稳定性和预存免疫反应较大程度上限制了疫苗免疫效果。为了解决这些问题，本论文利用磷酸钙盐（CaP）在一定条件下生物矿化携带SARS-CoV-2刺突蛋白（Spike, S）的重组新型腺病毒载体COVID-19疫苗Sad23L-nCoV-S，获得了一种生物矿化的Sad23L-nCoV-S-CaP疫苗。这种生物矿化的疫苗具有良好的热稳定性、免疫原性和规避预存针对腺病毒载体免疫反应的特点。Sad23L-nCoV-S-CaP疫苗在4℃保存45天、常温（26℃）保存8天和37℃保存2天均维持高水平的感染性滴度。此外，Sad23L-nCoV-S-CaP加强免疫小鼠，能够诱导产生高水平的S抗原特异性体液和细胞免疫反应，其免疫效果不会被预存的腺病毒载体Sad23L的高水平免疫反应削弱。因此，Sad23L-nCoV-S-CaP可以作为在Sad23L-nCoV-S疫苗初次免疫之后，进行加强免疫的候选疫苗。以这种免疫策略，Sad23L-nCoV-S初次免疫小鼠，4周之后，Sad23L-nCoV-S-CaP加强免疫，诱导产生了105.01的S1蛋白和104.77的S2蛋白特异性结合抗体水平，以及103.04中和抗体水平。此外，生物矿化疫苗诱导产生高水平特异性分泌干扰素-γ的T细胞反应为1466.16 spot forming cells (SFCs)/106 cells。因此，这种生物矿化的Sad23L-nCoV-S-CaP疫苗可以明显提高疫苗免疫效果，适合“初次+加强”的疫苗接种方案用于免疫预防SARS-CoV-2感染。
动物模型测试表明新冠灭活疫苗安全有效
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新冠病毒引起的COVID-19大流行给我们带来了前所未有的危机，对人类健康和生命造成巨大的威胁，给全球经济带来了灾难性的损失。截止目前全球新冠累计确诊患者数超过1.3亿，新冠感染导致的总死亡人数接近300万。因此开发有效的新冠疫苗迫在眉睫。本研究报道了中国科学院武汉病毒研究所、中国生物武汉生物制品研究所等单位联合研制的新冠灭活疫苗在小鼠和恒河猴上疫苗安全性、免疫原性和保护效果评价。结果显示该疫苗在小鼠和恒河猴体内均可诱导新冠特异性中和抗体产生。攻毒实验显示，疫苗高剂量组可对新冠病毒攻毒提供完全的保护，低剂量组亦可引起部分保护。小鼠被动免疫实验显示疫苗诱导的抗体可以对新冠病毒攻毒提供完全的保护。基于上述研究结果，为该疫苗进入临床研究打下坚实基础。
Structure and Function of N-Terminal Zinc Finger Domain of SARS-CoV-2 NSP2
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SARS-CoV-2已成为威胁人类健康和安全的全球性流行病。随着新型突变株的不断出现，寻找有效的治疗药物和靶点迫在眉睫。我们需要全面了解SARS-CoV-2在宿主细胞中的分子基础和发病机制。非结构蛋白2 (nsp2) 结构和功能的未知，阻碍了人们对其在SARS-CoV-2感染中的作用的理解。本文报道了SARS-CoV-2 nsp2的N端晶体结构，其分辨率达到1.96 Å。该结构包含三种锌指结构，分别属于C2H2、C4和C2HC类型。结构分析表明，nsp2可能参与结合核酸和调控细胞内信号通路。与单链或双链核酸的结合主要通过nsp2表面较大的正电荷区域，其中K111、K112、K113为关键的残基。我们的研究结果为更好地理解nsp2的结构与功能的关系奠定了基础。这有助于人们充分利用nsp2进行进一步的抗病毒靶点的研究和药物设计。
Human Endogenous Retrovirus Type W Envelope from Multiple Sclerosis Demyelinating Lesions Shows Unique Solubility and Antigenic Characteristics
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In multiple sclerosis (MS), human endogenous retrovirus W family (HERV-W) envelope protein, pHERV-W ENV, limits remyelination and induces microglia-mediated neurodegeneration. To better understand its role, we examined the soluble pHERV-W antigen from MS brain lesions detected by specific antibodies. Physico-chemical and antigenic characteristics confirmed differences between pHERV-W ENV and syncytin-1. pHERV-W ENV monomers and trimers remained associated with membranes, while hexamers self-assembled from monomers into a soluble macrostructure involving sulfatides in MS brain. Extracellular hexamers are stabilized by internal hydrophobic bonds and external hydrophilic moieties. HERV-W studies in MS also suggest that this diffusible antigen may correspond to a previously described high-molecular-weight neurotoxic factor secreted by MS B-cells and thus represents a major agonist in MS pathogenesis. Adapted methods are now needed to identify encoding HERV provirus(es) in affected cells DNA. The properties and origin of MS brain pHERV-W ENV soluble antigen will allow a better understanding of the role of HERVs in MS pathogenesis. The present results anyhow pave the way to an accurate detection of the different forms of pHERV-W ENV antigen with appropriate conditions that remained unseen until now.
一种抗体鸡尾酒疗法对SARS-CoV-2和SARS-CoV-2突变株具有广谱中和活性
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新型冠状病毒 ( SARS-CoV-2 )已产生多个对治疗性抗体耐药的突变株。本研究利用噬菌体展示技术，从新冠疫情暴发早期的恢复期病人外周血淋巴细胞中筛选出12株具有高亲和力的抗体。其中2株RBD蛋白结合抗体( F61和H121 )具有高亲和力的中和活性，3株S2蛋白结合抗体无中和活性。经结构分析，F61识别一个位于新冠S蛋白G446 - S494氨基酸位置的线性表位，与血管紧张素转换酶2 ( ACE2 )结合位点重叠； 而H121识别一个位于RBD侧面的构象表位，位于ACE2结合域之外。因此，这两种抗体配对使用的抗体鸡尾酒疗法对SARS-CoV-2具有更好的中和活性。重要的是，这2株抗体对B.1.1.7和B.1.351等新冠突变株也表现出较高中和活性。同时，这两株抗体可中和带有N501Y、E484K和L452R突变的新冠假病毒，表明这2株抗体也可能有效中和印度突变株B.1.617。F61和H121与多种带有单氨基酸突变的RBD蛋白结合活性不变，提示这两株抗体对新冠突变株具有广谱中和活性。我们的研究结果为SARS-CoV-2变异株抗体鸡尾酒疗法提供了理论基础，为SARS-CoV-2突变株感染者的临床治疗提供了候选广谱中和抗体。
Porcine Coronaviruses: Overview of the State of the Art
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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.
新型冠状病毒介导的炎症反应--从免疫机制到治疗策略
对于新型冠状病毒(SARS-CoV-2)感染造成的严重炎症反应和急性肺损伤，目前尚无有效治疗方法。鉴于SARS-CoV-2与SARS冠状病毒(SARS-CoV)的相似性，我们希望通过对SARS-CoV介导炎症反应机制的探讨，为SARS-CoV-2的临床治疗带来启示。我们认为可以通过抑制Fc受体(FcR)的活化来减少SARS-CoV-2诱导的炎症反应，但临床上目前尚无FcR特异性阻滞剂，因此在处理肺部急性炎症反应时，可以尝试应用免疫球蛋白来封闭Fc受体，避免进一步肺损伤的发生，这种治疗还可与全身性抗炎药物或皮质类固醇联合使用，该疗法的有效性仍需临床验证。
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, doi: 10.1016/j.virs.2022.03.007
收稿日期: 2021-09-02
录用日期: 2022-03-02
出版日期: 2022-03-11
Getah virus (GETV) is a mosquito-borne virus of the genus Alphavirus in the family Togaviridae and, in recent years, it has caused several outbreaks in animals. The molecular basis for GETV pathogenicity is not well understood. Therefore, a reverse genetic system of GETV is needed to produce genetically modified viruses for the study of the viral replication and its pathogenic mechanism. Here, we generated a CMV-driven infectious cDNA clone based on a previously isolated GETV strain, GX201808 (pGETV-GX). Transfection of pGETV-GX into BHK-21 cells resulted in the recovery of a recombinant virus (rGETV-GX) which showed similar growth characteristics to its parental virus. Then three-day-old mice were experimentally infected with either the parental or recombinant virus. The recombinant virus showed milder pathogenicity than the parental virus in the mice. Based on the established CMV-driven cDNA clone, subgenomic promoter and two restriction enzyme sites (BamHI and EcoRI) were introduced into the region between E1 protein and 3'UTR. Then the green fluorescent protein (GFP), red fluorescent protein (RFP) and improved light-oxygen-voltage (iLOV) genes were inserted into the restriction enzyme sites. Transfection of the constructs carrying the reporter genes into BHK-21 cells proved the rescue of the recombinant reporter viruses. Taken together, the establishment of a reverse genetic system for GETV provides a valuable tool for the study of the virus life cycle, and to aid the development of genetically engineered GETVs as vectors for foreign gene expression.
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, doi: 10.1016/j.virs.2022.03.005
收稿日期: 2021-09-07
录用日期: 2022-03-07
出版日期: 2022-03-11
Enteroviruses belonging to the family Picornaviridae are non-enveloped RNA viruses that cause hand-foot-mouth disease (HFMD), which can lead to severe neurological complications. Enteroviruses genomes represent a single open reading frame flanked by 5′-and 3′-untranslated terminal regions (UTRs), constituting the basis for classifying enteroviruses into groups A–D (Zaoutis et al., 1998). Current research is primarily focused on highly prevalent pathogens, including enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) of group A (Duan et al., 2021). However, group B viruses are also responsible for a significant number of infections that often cause histopathological changes in the heart, brain, and pancreas. For instance, coxsackievirus B5 (CV-B5) can induce aseptic meningitis, viral meningitis, acute flaccid paralysis, pancreatitis, and type I diabetes mellitus (Chen et al., 2020; Marcela et al., 2019; Hyöty et al., 2018). HFMD outbreaks caused by CV-B5 have been reported in China, Southeast Asia, and Europe. However, despite its clinical significance, little is known about its pathogenesis, and in-depth studies on the underlying mechanisms are urgently needed (Gao et al., 2018; Sciandra et al., 2020).
当前状态:
, 最新更新时间:
, doi: 10.1016/j.virs.2022.03.006
收稿日期: 2021-12-07
录用日期: 2022-03-07
出版日期: 2022-03-09
African swine fever (ASF) is a highly contagious and acute hemorrhagic viral disease with a high mortality approaching 100% in domestic pigs. ASF is an endemic in countries in sub-Saharan Africa. Now, it has been spreading to many countries, especially in Asia and Europe. Due to the fact that there is no commercial vaccine available for ASF to provide sustainable prevention, the disease has spread rapidly worldwide and caused great economic losses in swine industry. The knowledge gap of ASF virus (ASFV) pathogenesis and immune evasion is the main factor to limit the development of safe and effective ASF vaccines. Here, we will summarize the molecular mechanisms of how ASFV interferes with the host innate and adaptive immune responses. An in-depth understanding of ASFV immune evasion strategies will provide us with rational design of ASF vaccines.
当前状态:
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, doi: 10.1016/j.virs.2022.03.004
收稿日期: 2021-01-24
录用日期: 2022-03-07
出版日期: 2022-03-09
Avian influenza is a highly contagious viral infection affecting the respiratory system. MicroRNAs (miRNAs) are small, regulatory, endogenous, non-coding RNAs of ~22 nt that regulate the gene expression of the target mRNAs by cleavage or translational repression. miRNAs are connected with the host response during avian influenza virus (AIV) infection (Wang et al., 2009; Wang et al., 2012). In this study, we used miRNomics approach to understand the complex host-pathogen interaction during the HPAIV H5N1 infection in chicken.
当前状态:
, 最新更新时间:
, doi: 10.1016/j.virs.2022.03.003
收稿日期: 2021-11-10
录用日期: 2022-03-04
出版日期: 2022-03-07
The recent COVID-19 pandemic poses a global health emergency. Cellular entry of the causative agent SARS-CoV-2 is mediated by its spike protein interacting with cellular receptor-human angiotensin converting enzyme 2 (ACE2). Here, by using lentivirus based pseudotypes bearing spike protein, we demonstrated that entry of SARS-CoV-2 into host cells was dependent on clathrin-mediated endocytosis, and phosphoinositides played essential roles during this process. In addition, we showed that the intracellular domain and the catalytic activity of ACE2 were not required for efficient virus entry. Finally, we showed that the current predominant Delta variant, although with high infectivity and high syncytium formation, also entered cells through clathrin-mediated endocytosis. These results provide new insights into SARS-CoV-2 cellular entry and present proof of principle that targeting viral entry could be an effective way to treat different variant infections.
当前状态:
, 最新更新时间:
, doi: 10.1016/j.virs.2022.03.001
收稿日期: 2021-10-21
录用日期: 2022-02-25
出版日期: 2022-03-04
Hepatitis B surface antigen (HBsAg) clearance is considered as functional cure in patients with chronic hepatitis B (CHB). This study aimed to assess the durability of HBsAg clearance achieved by interferon-based therapies in patients with CHB who were originally positive for hepatitis B envelope antigen (HBeAg). In this prospective study, HBeAg-positive CHB patients with confirmed HBsAg loss under interferon-based therapies were enrolled within 12 weeks from end of treatment and followed up for 48 weeks. Virological markers, biochemical indicators, and liver imaging examinations were observed every 3–6 months. Sustained functional cure was analyzed as primary outcome. Factor associated with sustained HBsAg loss or reversion was also investigated. The rate of HBsAg loss sustainability was 91.8% (212/231). Patients receiving consolidation treatment for 12–24 weeks or ≥ 24 weeks had higher rates of sustained HBsAg negativity than those receiving consolidation treatment for < 12 weeks (98.3% and 91.2% vs. 86.7%, P = 0.068), and the former groups had significantly higher anti-HBs levels than the later (P < 0.05). The cumulative incidence of HBsAg reversion and HBV DNA reversion was 8.2% and 3.9%, respectively. Consolidation treatment of ≥ 12 weeks [odd ratio (OR) 3.318, 95% confidence interval (CI) 1.077–10.224, P = 0.037) was a predictor of sustained functional cure, and HBeAg-positivity at cessation of treatment (OR 12.271, 95% CI 1.076–139.919, P = 0.043) was a predictor of HBsAg reversion. Interferon-alpha induced functional cure was durable and a consolidation treatment of ≥ 12–24 weeks was needed after HBsAg loss in HBeAg-positive CHB patients.
当前状态:
, 最新更新时间:
, doi: 10.1016/j.virs.2022.03.002
收稿日期: 2021-11-11
录用日期: 2022-03-01
出版日期: 2022-03-04
African swine fever virus (ASFV), the sole member of the family Asfarviridae, is thecausative agent of African swine fever (ASF), a viral disease that leads to high mortality indomestic pigs. Since firstly identified in Kenya in the 1920s, ASFV has been prevalent inAfrica, Europe, and Russian Federation (Sanchez et al., 2019). Recently, ASFV wasintroduced to Asian countries including China, Mongolia, Vietnam, Cambodia, Laos andSouth Korea, which lead to huge economic losses to local pig industries (Li and Tian, 2018,Gaudreault and Richt, 2019). The first case of ASFV in China was reported in August 2018(Zhou et al., 2018). Since then, hundreds of cases in most provinces were officiallyannounced and more than 1 million pigs were slaughtered under the strict stamping-out policy(Miao et al., 2019).
当前状态:
, 最新更新时间:
, doi: 10.1016/j.virs.2022.02.010
收稿日期: 2021-09-25
录用日期: 2022-02-24
出版日期: 2022-03-03
Advancements in high-throughput sequencing (HTS) of antibody repertoires (Ig-Seq) have unprecedentedly improved our ability to characterize the antibody repertoires on a large scale. However, currently, only a few studies explored the influence of chronic HIV-1 infection on human antibody repertoires and many of them reached contradictory conclusions, possibly limited by inadequate sequencing depth and throughput. To better understand how HIV-1 infection would impact humoral immune system, in this study, we systematically analyzed the differences between the IgM (HIV-IgM) and IgG (HIV-IgG) heavy chain repertoires of HIV-1 infected patients, as well as between antibody repertoires of HIV-1 patients and healthy donors (HH). Notably, the public unique clones accounted for only a negligible proportion between the HIV-IgM and HIV-IgG repertoires libraries, and the diversity of unique clones in HIV-IgG remarkably reduced. In aspect of somatic mutation rates of CDR1 and CDR2, the HIV-IgG repertoire was higher than HIV-IgM. Besides, the average length of CDR3 region in HIV-IgM was significant longer than that in the HH repertoire, presumably caused by the great number of novel VDJ rearrangement patterns, especially a massive use of IGHJ6. Moreover, some of the B cell clonotypes had numerous clones, and somatic variants were detected within the clonotype lineage in HIV-IgG, indicating HIV-1 neutralizing activities. The in-depth characterization of HIV-IgG and HIV-IgM repertoires enriches our knowledge in the profound effect of HIV-1 infection on human antibody repertoires and may have practical value for the discovery of therapeutic antibodies.
当前状态:
, 最新更新时间:
, doi: 10.1016/j.virs.2022.02.009
收稿日期: 2021-08-10
录用日期: 2022-02-23
出版日期: 2022-02-28
Transformation-associated recombination (TAR) has been widely used to assemble large DNA constructs. One of the significant obstacles hindering assembly efficiency is the presence of error-prone DNA repair pathways in yeast, which results in vector backbone recircularization or illegitimate recombination products. To increase TAR assembly efficiency, we prepared a dual-selective TAR vector, pGFCS, by adding a PADH1-URA3 cassette to a previously described yeast-bacteria shuttle vector, pGF, harboring a PHIS3-HIS3 cassette as a positive selection marker. This new cassette works as a negative selection marker to ensure that yeast harboring a recircularized vector cannot propagate in the presence of 5-fluoroorotic acid. To prevent pGFCS bearing ura3 from recombining with endogenous ura3-52 in the yeast genome, a highly transformable Saccharomyces cerevisiae strain, VL6-48B, was prepared by chromosomal substitution of ura3-52 with a transgene conferring resistance to blasticidin. A 55-kb genomic fragment of monkeypox virus encompassing primary detection targets for quantitative PCR was assembled by TAR using pGFCS in VL6-48B. The pGFCS-mediated TAR assembly showed a zero rate of vector recircularization and an average correct assembly yield of 79% indicating that the dual-selection strategy provides an efficient approach to optimizing TAR assembly.
当前状态:
, 最新更新时间:
, doi: 10.1016/j.virs.2022.02.011
收稿日期: 2021-08-12
录用日期: 2022-02-24
出版日期: 2022-02-28
Human cytomegalovirus (HCMV) is a ubiquitous pathogen belongs to beta herpesvirus family. RNA2.7 is a highly conserved long non-coding RNA accounting for more than 20% of total viral transcripts. In our study, functions of HCMV RNA2.7 were investigated by comparison of host cellular transcriptomes between cells infected with HCMV clinical strain and RNA2.7 deleted mutant. It was demonstrated that RNA polymerase II (Pol II)-dependent host gene transcriptions were significantly activated when RNA2.7 was removed during infection. A 145 nt-in-length motif within RNA2.7 was identified to inhibit the phosphorylation of Pol II Serine-2 (Pol II S2) by reducing the interaction between Pol II and phosphorylated cyclin-dependent kinase 9 (pCDK9). Due to the loss of Pol II S2 phosphorylation, cellular DNA pre-replication complex (pre-RC) factors, including Cdt1 and Cdc6, were significantly decreased, which prevented more cells from entering into S phase and facilitated viral DNA replication. Our results provide new insights of HCMV RNA2.7 functions in regulation of host cellular transcription.
当前状态:
, 最新更新时间:
, doi: 10.1016/j.virs.2022.02.007
收稿日期: 2021-10-22
录用日期: 2022-02-21
出版日期: 2022-02-25
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. 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 including18 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.
当前状态:
, 最新更新时间:
, doi: 10.1016/j.virs.2022.02.008
收稿日期: 2021-07-20
录用日期: 2022-02-23
出版日期: 2022-02-25
Rabies virus (RABV) is an enveloped, non-segmented, and single-stranded RNA virus that belongs to the genus Lyssavirus within the Rhabdoviridae family (Douglas et.al., 2013). RABV causes rabies, and although vaccines are available, rabies continues to be a global public health concern causing more than 60,000 human deaths each year (WHO, 2013). There is a high prevalence especially in developing countries in Asia and Africa (Hampson et al., 2015; Singh et al., 2017). In most cases, RABV is transmitted through the direct contact of broken skin or the mucous membrane with the saliva of infected dogs. Unless the wound is promptly cleaned and post-exposure prophylaxis is administered, the human victim may develop encephalitis that is nearly always fatal.
当前状态:
, 最新更新时间:
, doi: 10.1016/j.virs.2022.02.006
收稿日期: 2021-03-25
录用日期: 2022-02-16
出版日期: 2022-02-18
Enterovirus 71 (EV71) belongs to the genus Enterovirus, family Picornaviridae (Oberste et al., 1999). It was first isolated from patients with central nervous system diseases in California between 1969 and 1974 (Schmidt et al., 1974) and has spread worldwide (Solomon et al., 2010). EV71 infection usually causes mild, self-limiting hand, foot, and mouth disease in children. Acute EV71 infection may also cause severe polio-like neurological diseases and significant mortality. The spectrum of EV71-associated neurological diseases includes aseptic meningitis, brainstem and/or cerebellar encephalitis, acute flaccid paralysis (AFP), myocarditis, and rapid fatal pulmonary edema and hemorrhage (McMinn, 2002).
当前状态:
, 最新更新时间:
, doi: 10.1016/j.virs.2022.02.005
收稿日期: 2022-01-23
录用日期: 2022-02-16
出版日期: 2022-02-18
Multiple new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have constantly emerged, as the delta and omicron variants, which have developed resistance to currently gained neutralizing antibodies. This highlights a critical need to discover new therapeutic agents to overcome the variants mutations. Despite the availability of vaccines against coronavirus disease 2019 (COVID-19), the use of broadly neutralizing antibodies has been considered as an alternative way for the prevention or treatment of SARS-CoV-2 variants infection. Here, we show that the nasal delivery of two previously characterized broadly neutralizing antibodies (F61 and H121) protected K18-hACE2 mice against lethal challenge with SARS-CoV-2 variants. The broadly protective efficacy of the F61 or F61/F121 cocktail antibodies was evaluated by lethal challenge with the wild strain (WIV04) and multiple variants, including beta (B.1.351), delta (B.1.617.2), and omicron (B.1.1.529) at 200 or 1000 TCID50, and the minimum antibody administration doses (5–1.25 mg/kg body weight) were also evaluated with delta and omicron challenge. Fully prophylactic protections were found in all challenged groups with both F61 and F61/H121 combination at the administration dose of 20 mg/kg body weight, and corresponding mice lung viral RNA showed negative, with almost all alveolar septa and cavities remaining normal. Furthermore, low-dose antibody treatment induced significant prophylactic protection against lethal challenge with delta and omicron variants, whereas the F61/H121 combination showed excellent results against omicron infection. Our findings indicated the potential use of broadly neutralizing monoclonal antibodies as prophylactic and therapeutic agent for protection of current emerged SARS-CoV-2 variants infection.
当前状态:
, 最新更新时间:
, doi: 10.1016/j.virs.2022.02.004
收稿日期: 2021-07-19
录用日期: 2022-02-10
出版日期: 2022-02-14
The Getah virus (GETV), a mosquito-borne RNA virus, is widely distributed in Oceania and Asia. GETV is not only pathogenic to horses, pigs, cattle, foxes and boars, but it can also cause fever in humans. Since its first reported case in Chinese mainland in 2017, the number of GETV-affected provinces has increased to seventeen till now. Therefore, we performed an epidemiologic investigation of GETV in the Xinjiang region, located in northwestern China, during the period 2017–2020. ELISA was used to analyze 3299 serum samples collected from thoroughbred horse, local horse, sheep, goat, cattle, and pigs, with thoroughbred horse (74.8%), local horse (67.3%), goat (11.7%), sheep (10.0%), cattle (25.1%) and pigs (51.1%) being positive for anti-GETV antibodies. Interestingly, the neutralizing antibody titer in horses was much higher than in other species. Four samples from horses and pigs were positive for GETV according to RT-PCR. Furthermore, from the serum of a local horse, we isolated GETV which was designated as strain XJ-2019-07, and determined its complete genome sequence. From the phylogenetic relationships, it belongs to the Group III lineage. This is the first evidence of GETV associated to domestic animals in Xinjiang. Overall, GETV is prevalent in Xinjiang and probably has been for several years. Since no vaccine against GETV is available in China, detection and monitoring strategies should be improved in horses and pigs, especially imported and farmed, in order to prevent economic losses.
当前状态:
, 最新更新时间:
, doi: 10.1016/j.virs.2022.02.003
收稿日期: 2021-05-24
录用日期: 2022-02-10
出版日期: 2022-02-12
Bovine hepacivirus (BovHepV) is a novel virus that was recently discovered in Ghana and Germany in 2015. Until now, this virus has been identified in cattle population worldwide and is classified into subtypes A–G. To fully understand the epidemic situation and genetic characteristic of BovHepV in China, a total of 612 cattle serum samples were collected from 20 farms in seven provinces and municipality in China between 2018 and 2020 and were tested for the presence of BovHepV RNA via semi-nested PCR. The results demonstrated that 49 (8.0%) samples were BovHepV RNA-positive. It is noted that BovHepV infection in yak was confirmed for the first time. BovHepV was detected in all the seven provinces, with the positive rate ranging from 3.1% to 13.3%, which indicates a wide geographical distribution pattern of BovHepV in China. Sequencing results revealed that 5′ UTR of the 49 field BovHepV strains have a nucleotide similarity of 96.3%–100% between each other and 93.9%–100% with previously reported BovHepV strains. In addition, genetic analysis identified five critical nucleotide sites in 5′ UTR to distinguish different subtypes, which was further verified by genomic sequencing and nucleotide similarity analysis. All the 49 Chinese field BovHepV strains were classified into subtype G and this subtype is only determined in cattle in China currently. This study will provide insights for us to better understand the epidemiology and genetic diversity of BovHepV.
当前状态:
, 最新更新时间:
, doi: 10.1016/j.virs.2022.02.002
收稿日期: 2021-04-07
录用日期: 2022-02-10
出版日期: 2022-02-12
Bocaviruses are associated with many human infectious diseases, such as respiratory tract infections, gastroenteritis, and hepatitis. Rats are known to be reservoirs of bocaviruses, including rodent bocavirus and rat bocavirus. Recently, ungulate bocaparvovirus 4, a known porcine bocavirus, has also been found in rats. Thus, investigating bocaviruses in rats is important for determining the origin of the viruses and preventing and controlling their transmission. To the best of our knowledge, no study to date has investigated bocaviruses in the livers of rats. In this report, a total of 624 rats were trapped in southern China between 2014 and 2017. Liver and serum samples from rats were tested for the prevalence of bocaviruses using PCR. Sequences related to ungulate bocaparvovirus 4 and rodent bocavirus were detected in both liver and serum samples. Interestingly, the prevalence of ungulate bocaparvovirus 4 (reference strain: KJ622366.1) was higher than that of rodent bocavirus (reference strain: KY927868.1) in both liver (2.24% and 0.64%, respectively) and serum samples (2.19% and 0.44%, respectively). The NS1 regions of ungulate bocaparvovirus 4 and rodent bocavirus related sequences displayed over 84% and 88% identity at the nucleic and amino acid levels, respectively. Furthermore, these sequences had similar genomic structure, genomic features, and codon usage bias, and shared a common ancestor. These viruses also displayed greater adaptability to rats than pigs. Our results suggested that ungulate bocaparvovirus 4 and rodent bocavirus may originate from rats and may be different genotypes of the same bocavirus species.
当前状态:
, 最新更新时间:
, doi: 10.1016/j.virs.2022.02.001
收稿日期: 2021-12-03
录用日期: 2022-01-24
出版日期: 2022-02-10
COVID-19 caused by SARS-CoV-2, is still a big threat to human populations around the world. As of Jan 2022, over 292 million cases were reported worldwide with more than 5.4 million deaths. After it was first reported in China in December 2019, the virus kept circulating and evolving and several variants with different transmissibility emerged in different countries and regions (WHO, 2021a). Until now, six major variants have been reported including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Lambda (C.37), and Omicron (B.1.1.529) and the infection caused by different variants has varied according to the surveillance data (WHO, 2021b).
当前状态:
, 最新更新时间:
, doi: 10.1016/j.virs.2022.01.029
收稿日期: 2021-09-26
录用日期: 2022-01-21
出版日期: 2022-01-29
Since its outbreak in 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) keeps surprising the medical community by evolving diverse immune escape mutations in a rapid and effective manner. To gain deeper insight into mutation frequency and dynamics, we isolated ten ancestral strains of SARS-CoV-2 and performed consecutive serial incubation in ten replications in a suitable and common cell line and subsequently analysed them using RT-qPCR and whole genome sequencing. Along those lines we hoped to gain fundamental insights into the evolutionary capacity of SARS-CoV-2 in vitro. Our results identified a series of adaptive genetic changes, ranging from unique convergent substitutional mutations and hitherto undescribed insertions. The region coding for spike proved to be a mutational hotspot, evolving a number of mutational changes including the already known substitutions at positions S:484 and S:501. We discussed the evolution of all specific adaptations as well as possible reasons for the seemingly inhomogeneous potential of SARS-CoV-2 in the adaptation to cell culture. The combination of serial passage in vitro with whole genome sequencing uncovers the immense mutational potential of some SARS-CoV-2 strains. The observed genetic changes of SARS-CoV-2 in vitro could not be explained solely by selectively neutral mutations but possibly resulted from the action of directional selection accumulating favourable genetic changes in the evolving variants, along the path of increasing potency of the strain. Competition among a high number of quasi-species in the SARS-CoV-2 in vitro population gene pool may reinforce directional selection and boost the speed of evolutionary change.
当前状态:
, 最新更新时间:
, doi: 10.1016/j.virs.2022.01.022
收稿日期: 2021-06-23
录用日期: 2021-10-20
出版日期: 2022-01-28
Temperate bacteriophages are widely distributed in bacteria isolated from different natural environments (Howard-Varona et al., 2017). The phages normally lead to lysogenic infection and merge their genetic components into the bacterial chromosome. Among the temperate phages, linear plasmid phages are atypical because of their capability to reside in host cells as linear dsDNA with covalently closed ends, rather than being integrated in host genomes in the form of prophages (Ravin et al., 2000; Ravin, 2011). The life cycle of N15, the first isolated linear plasmid phage, has been thoroughly investigated in its host Escherichia coli (Ravin, 2011). The formation of the linear plasmid prophage is attributed to a protelomerase that is encoded by the telN gene. The protelomerase acts on an inverted repeat site (telRL) on the phage genome, and then forms two covalently closed ends (telR and telL) (Ravin, 2003). Similar to phage λ DNA, N15 phage DNA has two 12-bp single-stranded cohesive ends (cosR and cosL), which are also responsible for the formation of the linear plasmid prophage of N15 (Ravin, 2015). Additionally, a multifunctional replication protein, RepA, which combines primase, helicase and DNA-binding activities, is indispensable for the lytic replication of N15 (Ravin, 2015).
当前状态:
, 最新更新时间:
, doi: 10.1016/j.virs.2022.01.032
收稿日期: 2020-10-07
录用日期: 2022-01-24
出版日期: 2022-01-28
Arthropod-borne chikungunya virus (CHIKV) infection can cause a debilitating arthritic disease in human. However, there are no specific antiviral drugs and effective licensed vaccines against CHIKV available for clinical use. Here, we developed an mRNA-lipid nanoparticle (mRNA-LNP) vaccine expressing CHIKV E2-E1 antigen, and compared its immunogenicity with soluble recombinant protein sE2-E1 antigen expressed in S2 cells. For comparison, we first showed that recombinant protein antigens mixed with aluminum adjuvant elicit strong antigen-specific humoral immune response and a moderate cellular immune response in C57BL/6 mice. Moreover, sE2-E1 vaccine stimulated 12–23 folds more neutralizing antibodies than sE1 vaccine and sE2 vaccine. Significantly, when E2-E1 gene was delivered by an mRNA-LNP vaccine, not only the better magnitude of neutralizing antibody responses was induced, but also greater cellular immune responses were generated, especially for CD8+ T cell responses. Moreover, E2-E1-LNP induced CD8+ T cells can perform cytotoxic effect in vivo. Considering its better immunogenicity and convenience of preparation, we suggest that more attention should be placed to develop CHIKV E2-E1-LNP mRNA vaccine.
当前状态:
, 最新更新时间:
, doi: 10.1016/j.virs.2022.01.031
收稿日期: 2021-02-20
录用日期: 2022-01-21
出版日期: 2022-01-25
The coronavirus disease 2019 (COVID-19) outbreak, has spread across the world (Wu et al., 2020). The causative agent of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly pathogenic and infectious, which become a major public health hazard that has had a devastating social and economic impact worldwide (Li QQ et al., 2020).
当前状态:
, 最新更新时间:
, doi: 10.1016/j.virs.2022.01.027
收稿日期: 2021-05-30
录用日期: 2021-10-18
出版日期: 2022-01-25
The hepatitis B virus (HBV) is a global public health challenge due to its highly contagious nature. It is estimated that almost 300 million people live with chronic HBV infection annually. Although nucleoside analogs markedly reduce the risk of liver disease progression, the analogs do not fully eradicate the virus. As such, new treatment options and drugs are urgently needed. Psoralen is a nourishing monomer of Chinese herb and is known to inhibit virus replication and inactivate viruses. In this study, we evaluated the potential of psoralen as an anti-HBV agent. Quantitative PCR and Southern blot analysis revealed that psoralen inhibited HBV replication in HepG2.2.15 cells in a concentration-dependent manner. Moreover, psoralen was also active against the 3TC/ETV-dual-resistant HBV mutant. Further investigations revealed that psoralen suppressed both HBV RNA transcription and core protein expression. The transcription factor FOXO1, a known target for PGC1α co-activation, binds to HBV pre-core/core promoter enhancer II region and activates HBV RNA transcription. Co-immunoprecipitation showed that psoralen suppressed the expression of FOXO1, thereby decreasing the binding of FOXO1 co-activator PGC1α to the HBV promoter. Overall, our results demonstrate that psoralen suppresses HBV RNA transcription by down-regulating the expression of FOXO1 resulting in a reduction of HBV replication.
当前状态:
, 最新更新时间:
, doi: 10.1016/j.virs.2022.01.030
收稿日期: 2021-10-23
录用日期: 2022-01-21
出版日期: 2022-01-25
The nationwide COVID-19 epidemic ended in 2020, a few months after its outbreak in Wuhan, China at the end of 2019. Most COVID-19 cases occurred in Hubei Province, with a few local outbreaks in other provinces of China. A few studies have reported the early SARS-CoV-2 epidemics in several large cities or provinces of China. However, information regarding the early epidemics in small and medium-sized cities, where there are still traditionally large families and community culture is more strongly maintained and thus, transmission profiles may differ, is limited. In this study, we characterized 60 newly sequenced SARS-CoV-2 genomes from Anyang as a representative of small and medium-sized Chinese cities, compared them with more than 400 reference genomes from the early outbreak, and studied the SARS-CoV-2 transmission profiles. Genomic epidemiology revealed multiple SARS-CoV-2 introductions in Anyang and a large-scale expansion of the epidemic because of the large family size. Moreover, our study revealed two transmission patterns in a single outbreak, which were attributed to different social activities. We observed the complete dynamic process of single-nucleotide polymorphism development during community transmission and found that intrahost variant analysis was an effective approach to studying cluster infections. In summary, our study provided new SARS-CoV-2 transmission profiles representative of small and medium-sized Chinese cities as well as information on the evolution of SARS-CoV-2 strains during the early COVID-19 epidemic in China.
当前状态:
, 最新更新时间:
, doi: 10.1016/j.virs.2022.01.028
收稿日期: 2021-09-17
录用日期: 2022-01-14
出版日期: 2022-01-24
Coxsackievirus A10 (CVA10) is one of the major causative agents of hand, foot and mouth disease (HFMD). To investigate the epidemiological characteristics as well as genetic features of CVA10 currently circulating in Shanghai, China, we collected a total of 9,952 sporadic HFMD cases from January 2016 to December 2020. In the past five years, CVA10 was the fourth prevalent causatives associated with HFMD in Shanghai and the overall positive rate was 2.78%. The annual distribution experienced significant fluctuations over the past five years. In addition to entire VP1 sequencing, complete genome sequencing and recombination analysis of CVA10 isolates in Shanghai were further performed. A total of 64 near complete genomes and 11 entire VP1 sequences in this study combined with reference sequences publicly available were integrated into phylogenetic analysis. The CVA10 sequences in this study mainly belonged to genogroup C and presented 91%–100% nucleotide identity with other Chinese isolates based on VP1 region. For the first time, our study reported the appearance of CVA10 genogroup D in Chinese mainland, which had led to large-scale outbreaks in Europe previously. The recombination analysis showed the recombination break point located between 5,100 nt and 6,700 nt, which suggesting intertypic recombination with CVA16 genogroup D. To conclusion, CVA10 genogroup C was the predominant genogroup in Shanghai during 2016–2020. CVA10 recombinant genogroup D was firstly reported in circulating in Chinese mainland. Continuous surveillance is needed to better understand the evolution relationships and transmission pathways of CVA10 to help to guide disease control and prevention.
当前状态:
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, doi: 10.1016/j.virs.2022.01.025
收稿日期: 2021-05-26
录用日期: 2022-01-14
出版日期: 2022-01-24
Porcine deltacoronavirus (PDCoV) is a novel discovered swine enteric coronavirus which can cause diarrhea and dehydration in pigs, particularly in neonatal piglets (Jung et al. 2016). At present, there are no commercial vaccines available for PDCoV. To control PDCoV transmission and perform antiviral therapy efficiently, a rapid and accurate diagnostic method to detect PDCoV is needed. PDCoV nucleocapsid (N) protein is the most abundant protein in the virus particle and plays essential roles in several stages of the viral lifecycle. It can produce high levels of antibodies at the early stage of PDCoV infection (Xu et al. 2013; Dinesh et al. 2020; Van Elslande et al. 2021). However, the characterization of epitopes on PDCoV N protein remains largely unknown.
当前状态:
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, doi: 10.1016/j.virs.2022.01.023
收稿日期: 2021-06-09
录用日期: 2021-10-08
出版日期: 2022-01-22
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. Histopathological examination 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.
当前状态:
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, doi: 10.1016/j.virs.2022.01.024
收稿日期: 2021-01-28
录用日期: 2022-01-14
出版日期: 2022-01-22
Coxsackievirus A24 variant (CVA24v) is a major pathogen that causes continued outbreaks and pandemics of acute hemorrhagic conjunctivitis (AHC). In China, the first confirmed outbreak of CVA24v-related AHC occurred in Beijing in 1988, followed by another two significant outbreaks respectively in 1994 and 2007, which coincides with the three-stage dynamic distribution of AHC in the world after 1970s. To illustrate the genetic characteristics of CVA24v in different periods, a total of 23 strains were isolated from those three outbreaks and the whole genome of those isolations were sequenced and analyzed. Compared with the prototype strain, the 23 strains shared four nucleotide deletions in the 5′ UTR except the 0744 strain isolated in 2007. And at the 98th site, one nucleotide insertion was found in all the strains collected from 2007. From 1994 to 2007, amino acid polarity in the VP1 region at the 25th and the 32nd site were changed. Both the 3C and VP1 phylogenetic tree indicated that isolates from 1988 and 1994 belonged to Genotype III (GIII), and 2007 strains to Genotype IV (GIV). According to the Bayesian analysis based on complete genome sequence, the most recent common ancestors for the isolates in 1988, 1994 and 2007 were respectively estimated around October 1987, February 1993 and December 2004. The evolutionary rate of the CVA24v was estimated to be 7.45 × 10−3 substitutions/site/year. Our study indicated that the early epidemic of CVA24v in Chinese mainland was the GIII. Point mutations and amino acid changes in different genotypes of CVA24v may generate intensity differences of the AHC outbreak. CVA24v has been evolving constantly with a relatively rapid rate.
当前状态:
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, doi: 10.1016/j.virs.2022.01.026
收稿日期: 2021-06-16
录用日期: 2021-12-27
出版日期: 2022-01-22
Subgroup J avian leukosis virus (ALV-J) is a highly oncogenic retrovirus that has been devastating the global poultry industry since the late 1990s. The major infection model of ALV-J is vertical transmission, which is responsible for the congenital infection of progeny from generation to generation. Increasing evidence has suggested that extracellular vesicles (EVs) derived from virus-infected cells or biological fluids have been thought to be vehicles of transmission for viruses. However, the role of EVs in infection and transmission of ALV-J remains obscure. In the present study, semen extracellular vesicles (SE) were isolated and purified from ALV-J-infected rooster seminal plasma (SE-ALV-J), which was shown to contain ALV-J genomic RNA and partial viral proteins, as determined by RNA sequencing, reverse transcription-quantitative PCR and Western blotting. Furthermore, SE-ALV-J was proved to be able to transmit ALV-J infection to host cells and establish productive infection. More importantly, artificial insemination experiments showed that SE-ALV-J transmitted ALV-J infection to SPF hens, and subsequently mediated vertical transmission of ALV-J from the SPF hens to the progeny chicks. Taken together, the results of the present study suggested that ALV-J utilized host semen extracellular vesicles as a novel means for vertical transmission, enhancing our understanding on mechanisms underlying ALV-J transmission.
当前状态:
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, doi: 10.1016/j.virs.2022.01.016
收稿日期: 2021-07-28
录用日期: 2021-10-10
出版日期: 2022-01-19
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.
Analysis of severe human adenovirus infection outbreak in Guangdong Province, southern China in 2019
当前状态:
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, doi: 10.1016/j.virs.2022.01.010
收稿日期: 2021-07-07
录用日期: 2021-12-06
出版日期: 2022-01-17
During 2018–2019, a severe human adenovirus (HAdV) infection outbreak occurred in southern China. Here, we screened 18 respiratory pathogens in 1,704 children (≤14 years old) hospitalized with acute respiratory illness in Guangzhou, China, in 2019. In total, 151 patients had positive HAdV test results; 34.4% (52/151) of them exhibited severe illness. HAdV infection occurred throughout the year, with a peak in summer. The median patient age was 3.0 (interquartile range: 1.1–5.0) years. Patients with severe HAdV infection exhibited increases in 12 clinical indexes (P ≤ 0.019) and decreases in four indexes (P ≤ 0.007), compared with patients exhibiting non-severe infection. No significant differences were found in age or sex distribution according to HAdV infection severity (P > 0.05); however, the distributions of comorbid disease and HAdV co-infection differed according to HAdV infection severity (P < 0.05). The main epidemic types were HAdV-3 (47.0%, 71/151) and HAdV-7 (46.4%, 70/151). However, the severe illness rate was significantly higher in patients with HAdV-7 (51.4%) than in patients with HAdV-3 (19.7%) and other types of HAdV (20%) (P < 0.001). Sequencing analysis of genomes/capsid genes of 13 HAdV-7 isolates revealed high similarity to previous Chinese isolates. A representative HAdV-7 isolate exhibited a similar proliferation curve to the curve described for the epidemic HAdV-3 strain Guangzhhou01 (accession no. DQ099432) (P > 0.05); the HAdV-7 isolate exhibited stronger virulence and infectivity, compared with HAdV-3 (P < 0.001). Overall, comorbid disease, HAdV co-infection, and high virulence and infectivity of HAdV-7 were critical risk factors for severe HAdV infection; these data can facilitate treatment, control, and prevention of HAdV infection.
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, doi: 10.1016/j.virs.2022.01.013
收稿日期: 2021-08-30
录用日期: 2021-11-04
出版日期: 2022-01-17
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.
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, doi: 10.1016/j.virs.2022.01.002
收稿日期: 2021-02-23
录用日期: 2021-08-04
出版日期: 2022-01-12
Severe acute respiratory syndrome (SARS) is a highly contagious zoonotic disease caused by SARS coronavirus (SARS-CoV). Since its outbreak in Guangdong Province of China in 2002, SARS has caused 8096 infections and 774 deaths by December 31st, 2003. Although there have been no more SARS cases reported in human populations since 2004, the recent emergence of a novel coronavirus disease (COVID-19) indicates the potential of the recurrence of SARS and other coronavirus disease among humans. Thus, developing a rapid response SARS vaccine to provide protection for human populations is still needed. Spike (S) protein of SARS-CoV can induce neutralizing antibodies, which is a pivotal immunogenic antigen for vaccine development. Here we constructed a recombinant chimeric vesicular stomatitis virus (VSV) VSVΔG-SARS, in which the glycoprotein (G) gene is replaced with the SARS-CoV S gene. VSVΔG-SARS maintains the bullet-like shape of the native VSV, with the heterogeneous S protein incorporated into its surface instead of G protein. The results of safety trials revealed that VSVΔG-SARS is safe and effective in mice at a dose of 1 × 106 TCID50. More importantly, only a single-dose immunization of 2 × 107 TCID50 can provide high-level neutralizing antibodies and robust T cell responses to non-human primate animal models. Thus, our data indicate that VSVΔG-SARS can be used as a rapid response vaccine candidate. Our study on the recombinant VSV-vectored SARS-CoV vaccines can accumulate experience and provide a foundation for the new coronavirus disease in the future.
2022, 37(1): 1-10.
doi: 10.1016/j.virs.2022.01.017
收稿日期: 2021-07-31
录用日期: 2021-11-15
出版日期: 2022-01-19
尽管在预防HIV-1感染和治疗艾滋病(AIDS)方面做出了巨大努力，HIV-1/AIDS仍然是全球人类健康的重大威胁。目前广泛使用的联合抗逆转录病毒疗法（Combination antiretroviral therapy，CART）虽然可以抑制HIV-1复制，但不能彻底清除整合在人免疫细胞基因组中的前病毒DNA，该方法需要艾滋病患者终身服药进行治疗，长期的药物治疗会带来多种副反应。近年来，成簇的规律间隔的短回文重复序列及其相关蛋白9[clustersd regularly interspaced short panlindromic repet (CRISPR) /CRISPR-associated nuclease 9（Cas9），CRISPR/Cas9]基因编辑系统被利用并开发设计成了一种抵御HIV-1感染和治疗艾滋病的有效工具。此外，一些来自于或功能类似于CRISPR/Cas9的新基因打靶工具，例如碱基编辑器(base editor)、启动编辑器(prime editing)、SHERLOCK、DETECTR、PAC-MAN、ABACAS、pfAGO等，已经被开发和优化并用于病原体检测和疾病的治疗。本文综述了近年来HIV-1/AIDS基因治疗的最新研究进展，并结合HIV-1感染的新分子机制提供了更多的基因编辑靶点。该文章还论述了这些新的基因编辑技术在未来HIV-1/AIDS治疗中的新策略和潜在应用。此外，我们讨论了这些多功能基因编辑工具在临床使用之前值得注意并解决的关键问题。最后，我们提出了改进基因编辑在HIV-1/AIDS基因治疗中的替代方案。
2022, 37(1): 11-18.
doi: 10.1016/j.virs.2022.01.019
收稿日期: 2021-08-18
录用日期: 2021-10-12
出版日期: 2022-01-19
逆转录病毒广泛感染脊椎动物，可引起多种疾病。逆转录病毒的复制过程需要将病毒的遗传物质RNA逆转录成DNA并整合到宿主基因组中。当逆转录病毒感染生殖细胞时，整合的逆转录病毒便会从亲代遗传到子代，形成内源性逆转录病毒。内源性逆转录病毒记录了远古发生的病毒感染事件，因此为研究逆转录病毒的远古进化提供了重要的“分子化石”。本文从病毒“化石”视角系统总结了关于逆转录病毒多样性和进化的最新研究进展，并探讨了内源性逆转录病毒对宿主生物学进化的影响。
2022, 37(1): 19-29.
doi: 10.1016/j.virs.2021.12.001
收稿日期: 2021-04-29
录用日期: 2021-08-28
出版日期: 2021-12-17
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。
2022, 37(1): 30-37.
doi: 10.1016/j.virs.2022.01.008
收稿日期: 2021-04-28
录用日期: 2021-12-29
出版日期: 2022-01-17
人们对于感染2019新型冠状病毒(COVID-19)患者的亚基因组RNA (sgRNA)动态变化知之甚少。所以我们收集了来自117例中国LOTUS试验(ChiCTR2000029308)的COVID-19患者的147个咽拭子、74个肠道拭子和46个血浆样本，并比较了不同病程、结局和合并症的患者E基因和orf7a 基因sgRNA载量。在三种类型样本中均检测到这两种sgRNA, E sgRNA可检测到的最长时间为25、13和17天，orf7a sgRNA可检测到的最长时间分别为32、28和17天。治疗10天后，95%(57/60)的患者未检测到E sgRNA，但仍有86%的患者E RNA阳性。同一样本中E基因和orf7a基因的sgRNA含量高度相关。标准治疗组和洛匹那韦-利托那韦组的sgRNA变化相似。糖尿病和心脏病患者治疗后第1天的咽部E sgRNA较无此类合并症的患者高(P = 0.016和0.013)，而第5天则无差异。合并高血压和脑血管疾病患者在治疗1天后和5天后咽部sgRNA水平与没有这两种合并症的患者相比均无差异。初始感染时E sgRNA水平与发现感染后10天血清内抗刺突蛋白、核蛋白和受体结合域抗体水平无相关性。sgRNA在COVID-19患者中持续时间较长，可能对体液免疫影响不大。
2022, 37(1): 38-47.
doi: 10.1016/j.virs.2022.01.001
收稿日期: 2021-04-02
录用日期: 2021-07-22
出版日期: 2022-01-13
自2016年中旬以来，低致病性H7N9流感病毒在我国演变为高致病性H7N9流感病毒，对家禽产业和公共卫生构成了极大的威胁。在高致病性H7N9流感病毒流行的早期，其裂解位点主要插入“KRTA”基序。随着H7N9流感病毒的传播，禽源和人源高致病性H7N9流感病毒的裂解位点更具有多态性，表现出碱性和非碱性氨基酸插入和氨基酸的替换，但这些插入和替换的潜在功能仍不清楚。在这里，我们通过反向遗传技术拯救出6株携带PEIPKGR/G、PEVPKGR/G、PEVPKRKRTAR/G、PEVPKGKRTAR/G、PEVPKGKRIAR/G和PEVPKRKRR/G基序的H7N9流感病毒。我们的研究结果表明，PEVPKRKRTAR/G基序的氨基酸插入在我国流行的高致病性H7N9病毒中占主导地位。有趣的是，删除H7N9病毒裂解位点的苏氨酸和丙氨酸后，H7N9病毒显著降低了热稳定性并且降低小鼠致病性。含有PEVPKRKRTAR/G基序的病毒在鸡上能够增强致病性，但是与其他高致病性H7N9病毒相比，其在鸡上的传播能力有所降低。以上结论解释了为何含有PEVPKRKRTAR/G基序的H7N9病毒在我国能够持续流行。与此相反，携带异亮氨酸和丙氨酸的H7N9病毒可降低鸡的传播率和小鼠的毒力。值得注意的是，H7N9病毒的HA蛋白的I335V氨基酸突变能够显著增强鸡的致病性和传播能力，表明H7N9的碱性氨基酸和非碱性氨基酸的联合插入以及裂解位点处I335V的替换促进了鸡和小鼠的复制能力和致病性。随着H7N9病毒的不断进化，其对家禽养殖业和人类健康的威胁越来越大，因此需要加强H7N9病毒的全面监测和预防。
2022, 37(1): 48-59.
doi: 10.1016/j.virs.2022.01.004
收稿日期: 2021-06-23
录用日期: 2021-09-15
出版日期: 2022-01-12
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。
2022, 37(1): 60-69.
doi: 10.1016/j.virs.2022.01.003
收稿日期: 2021-07-21
录用日期: 2021-09-03
出版日期: 2022-01-13
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。
2022, 37(1): 70-81.
doi: 10.1016/j.virs.2022.01.011
收稿日期: 2021-07-28
录用日期: 2022-01-07
出版日期: 2022-01-18
猪流行性腹泻病毒(Porcine epidemic diarrhea virus, PEDV)是引起猪腹泻、呕吐和死亡的主要原因，给全球养猪业造成了毁灭性的经济损失。近年来，随着RNA测序技术的发展，宿主感染PEDV后的晚期反应得以被研究；然而，目前尚没有针对宿主感染PEDV强毒株和弱毒株后早期反应的研究。因此，我们对猪肠道上皮细胞（IPEC-J2）感染PEDV强毒株(GDS01)或弱毒株(HX)3、6和12 h后的表达谱进行转录组学测序分析。结果显示，超过一半的差异表达基因在两个感染组中均表现出下调表达的模式。功能富集分析显示，GDS01组差异表达基因主要与自噬和凋亡通路相关，而HX组差异表达基因主要在免疫应答/炎症反应通路中富集。在差异表达基因中，TLR3和IFIT2基因与HX和GDS01毒株的增值速度有关，并通过TLR3抑制试验和IFIT2过表达试验在体外进行了验证。TLR3通过增强IFIT2的表达从而抑制了HX株的复制，而对GDS01株没有显著影响。综上，我们的研究揭示了PEDV强毒株和弱毒株感染早期基因表达模式和细胞过程/通路的异同，这些发现可能为控制PEDV的感染及新型治疗方法的研制奠定基础。
2022, 37(1): 82-93.
doi: 10.1016/j.virs.2022.01.012
收稿日期: 2020-08-09
录用日期: 2021-12-06
出版日期: 2022-01-17
腹泻是发展中国家五岁以下儿童死亡的第三大原因。每年约有50万儿童死于腹泻，其中大部分发生在发展中国家。病毒是腹泻的主要病原体。在中国，对于腹泻儿童粪便病毒组的研究较少。使用无偏差病毒宏基因组学方法，我们分析了腹泻儿童的粪便病毒组。在这些粪便样本中发现的许多与腹泻相关的DNA或RNA病毒主要来自腺病毒科、星状病毒科、杯状病毒科、细小病毒科、小核糖核酸科和呼肠病毒科。其中，杯状病毒科所占比例最大，为78.42%，其次是腺病毒科（8.94%）和小核糖核酸科（8.36%）。除了那些已经被证实能引起人类腹泻的腹泻相关病毒外，还发现了与腹泻无关的病毒，包括指环病毒和双小RNA病毒。这项研究不仅增加了我们对腹泻儿童粪便病毒组的了解，并为该地区病毒性腹泻的预防和治疗提供了有价值的资料。
2022, 37(1): 94-106.
doi: 10.1016/j.virs.2022.01.007
收稿日期: 2021-03-15
录用日期: 2021-10-12
出版日期: 2022-01-18
黄病毒是重要的蚊媒传播的病原体，对全球人类和动物健康造成了严重的危害，但目前仍没有有效的针对黄病毒的治疗药物。脱氢表雄酮 (DHEA) 是一种天然存在于人体内的肾上腺衍生类固醇，与预防各种感染有关。在本研究中，对32种DHEA合成衍生物进行了抗黄病毒效果的检测。根据初步筛选，HAAS-AV3026 和 HAAS-AV3027 用于后续实验，这些衍生物对 JEV（IC50= 2.13和1.98 μM）和 ZIKV（IC50= 3.73和3.42 μM）表现出很强的抗病毒活性。机制研究表明，两种衍生物对黄病毒的吸附和入侵过程没有抑制作用，但是在复制阶段显著抑制黄病毒感染。此外，间接免疫荧光检测、蛋白质印迹分析和荧光定量PCR反应揭示了 DHEA 衍生物在抑制病毒感染、蛋白质生成和病毒 RNA 合成方面对 JEV 和 ZIKV 的强效抗病毒活性。综合起来，我们的结果可能为开发针对黄病毒的新抗病毒药物奠定了基础。
2022, 37(1): 107-114.
doi: 10.1016/j.virs.2022.01.018
收稿日期: 2021-08-11
录用日期: 2021-10-12
出版日期: 2022-01-20
SFTS病毒（SFTSV）感染引起的严重发热伴血小板减少综合征（SFTS）2010年在中国首次报道，致死率高达30%。通过检测病毒RNA或抗体水平来确认SFTSV感染对于SFTS的诊断和治疗至关重要。本研究建立了一种新型的荧光素酶免疫沉淀系统（LIPS），该系统pREN2质粒系统融合表达SFTSV 核蛋白NP与海参荧光素酶（Rluc），通过测定Rluc的酶活反应水平检测血液样本中抗SFTSV抗体应答水平。对2019年从浙江省绍兴市医院共采集的464份发热患者血清样本进行LIPS检测，发现4有82例病人（17.7%）为SFTSV抗体阳性。该结果也得到了免疫荧光实验验证。此外，qRT-PCR和微量中和实验显示，82例阳性病例中，有15例患者有病毒血症，10例患者血清表现病毒中和活性，1例患者血清样本中同时检测到病毒血症和中和抗体，提示至少有上述共26例患者存在对SFTSV的感染暴露。然而，回顾患者医疗诊断记录和疾病相关临床检测指标，显示这些患者均没有被诊断为SFTS，可能与他们的症状轻微或亚临床表现有关。因此，研究结果提示：很可能存在SFTS漏诊病例， SFTS的实际发病率很可能高于记录和报告的水平。研究也证明了LIPS作为一种新兴的总抗体水平检测方法，可以成为SFTSV感染病例的实验室确诊的一种有效的手段。
2022, 37(1): 115-126.
doi: 10.1016/j.virs.2022.01.021
收稿日期: 2021-09-09
录用日期: 2021-10-20
出版日期: 2022-01-21
寨卡病毒可以感染包括人类胎儿发育性大脑在内的多种组织。特定的病毒基因变异是否与神经病理学有关尚不完全清楚。为了解决这一问题，我们在新生小鼠中连续传代了一株寨卡病毒临床分离株 (SW01)，发现连续传代可导致病毒毒性显著增加和神经向性的变异。深度测序分析结合分子病毒学研究表明，E蛋白上第67位氨基酸单一位点天冬氨酸（D）到天冬酰胺（N）的突变（D67N）足以显著增加病毒毒力和体内神经嗜性。值得注意的是，D67N突变的病毒克隆在体外的人神经星形胶质细胞U251细胞中具有更高的病毒产量，并引起更严重的细胞病变效应(CPE)，表明其对人脑具有潜在的神经毒性。这些发现表明，ZIKV包膜上的单一突变D67N可能导致严重的神经损伤，这可能有助于解释ZIKV的神经毒性，并提示在自然感染期间监测这种突变的发生可能很重要。
2022, 37(1): 127-137.
doi: 10.1016/j.virs.2022.01.015
收稿日期: 2021-10-25
录用日期: 2021-11-12
出版日期: 2022-01-18
克里米亚-刚果出血热病毒(Crimean-Congo hemorrhagic fever virus, CCHFV)是一种引起人类严重出血性疾病的病原体，致死率高。CCHFV囊膜表面糖蛋白Gc在CCHFV入侵靶细胞过程中介导病毒与宿主膜融合，同时也是中和抗体的主要免疫靶标，因此其结构信息对于阐明病毒膜融合机制和研究中和抗体的中和机制至关重要，但到目前为止对CCHFV糖蛋白Gc的结构研究相对较少，尚无其胞外域蛋白结构的相关报道。
我们设计了Gc胞外域的三聚体蛋白，利用单颗粒分析技术解析了2.8 Å分辨率的Gc融合后结构，证实CCHFV糖蛋白Gc是II型膜融合蛋白。与布尼亚家族白纤病毒科和汉坦病毒科病毒已解析的Gc蛋白融合后结构进行结构、序列比较，发现CCHFV的Gc结构域III的排布方式与白纤病毒相似；但是其结构域II顶端的融合肽则与汉坦病毒的结构保守性较高。由于存在这种混合结构特征，我们推测在进化上CCHFV与这两种病毒均存在关联。Gc的结构解析，还帮助我们定位了Gc的抗原表位，因此提供了重要的结构信息以便分析各种抗体潜在的中和机制。
我们设计了Gc胞外域的三聚体蛋白，利用单颗粒分析技术解析了2.8 Å分辨率的Gc融合后结构，证实CCHFV糖蛋白Gc是II型膜融合蛋白。与布尼亚家族白纤病毒科和汉坦病毒科病毒已解析的Gc蛋白融合后结构进行结构、序列比较，发现CCHFV的Gc结构域III的排布方式与白纤病毒相似；但是其结构域II顶端的融合肽则与汉坦病毒的结构保守性较高。由于存在这种混合结构特征，我们推测在进化上CCHFV与这两种病毒均存在关联。Gc的结构解析，还帮助我们定位了Gc的抗原表位，因此提供了重要的结构信息以便分析各种抗体潜在的中和机制。
2022, 37(1): 138-141.
doi: 10.1016/j.virs.2022.01.006
收稿日期: 2021-05-31
录用日期: 2021-09-30
出版日期: 2022-01-13
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus that causes the outbreak of coronavirus disease 2019 (COVID-19) (Li et al., 2020a). Viral nucleic acid testing is the standard method for the laboratory diagnosis of COVID-19 (Wu et al., 2020a; Zhu et al., 2020). Currently, a variety of qPCR-based detection kits are used for laboratory-based detection and confirmation of SARS-CoV-2 infection (Corman et al., 2020; Hussein et al., 2020; Ruhan et al., 2020; Veyer et al., 2020). Conventional qPCR involves virus inactivation, nucleic acid extraction, and qPCR amplification procedures. Therefore, the process is complicated, which usually takes longer than 2 h, and requires biosafety laboratories and professional staff. Thus, qPCR is not suitable for use in field or medical units. To reduce the operation steps, automatic integrated qPCR detection systems that combine nucleic acid extraction and qPCR amplification in a sealed cartridge were developed to detect viruses in clinical samples (Li et al., 2020b). However, the detection time is still longer than 1 h. Therefore, rapid nucleic acid detection systems are needed to further improve the detection efficiency.
2022, 37(1): 142-144.
doi: 10.1016/j.virs.2022.01.020
收稿日期: 2021-08-26
录用日期: 2022-01-12
出版日期: 2022-01-20
最近在冷冻鱼中检测到新冠病毒的报道引起了人们对鱼类在新冠病毒传播中的潜在作用的担忧。 本研究调查了鱼类 ACE2 对新冠病毒的易感性。为了确定这一点，我们用新冠病毒感染了三种鱼细胞系（鲤鱼上皮细胞、草鱼肾脏细胞和蓝鳃太阳鱼细胞)。 此外，我们在 Hela 细胞中表达了五种鱼 ACE2（斑马鱼、罗非鱼、鲶鱼、鲑鱼和虹鳟鱼）并感染了新冠病毒。 通过免疫荧光测定 (IFA) 和定量逆转录聚合酶链反应 (qRT-PCR)，在鱼细胞系或 Hela 细胞表达的鱼 ACE2 中未检测到病毒抗原。综上所述，IFA 和 qRT-PCR 结果证实新冠病毒不能与鱼类 ACE2 结合以侵入宿主细胞。
2022, 37(1): 145-148.
doi: 10.1016/j.virs.2022.01.014
收稿日期: 2021-09-08
录用日期: 2021-11-25
出版日期: 2022-01-18
严重发热伴血小板减少综合征病毒（SFTSV）是一种新型病原体，于2009年在我国首次分离得到。近年来，该病在东亚地区多次暴发，但尚无疫苗或药物获批用于治疗这一新型布尼亚病毒感染。本研究中，我们首先构建了一个基于细胞病变效应（cytopathological effect，CPE）的高通量药物筛选模型。在此基础上，发现已上市药物替洛隆（Tilorone）具有良好的抗SFTSV活性。经进一步验证，我们发现替洛隆在体外和体内均可以通过激活天然免疫反应抑制SFTSV感染，并对SFTSV感染表现出良好预防作用。
2022, 37(1): 149-152.
doi: 10.1016/j.virs.2022.01.005
收稿日期: 2020-07-12
录用日期: 2021-08-09
出版日期: 2022-01-13
Arthropod-borne viruses are a group of the most important emerging pathogens. They cause a range of diseases in vertebrate hosts and threaten human health (Gan and Leo, 2014). The global distribution of arboviruses is associated with the vector which is strongly affected by changes in environmental conditions. Dengue virus (DENV) and Chikungunya virus (CHIKV), which cause high annual infected cases and have an increasing geographic distribution, are transmitted by Aedes spp. mosquitoes, in particular Ae. albopictus and Ae. Aegypti (Presti et al., 2014; Higuera and Ramírez, 2018). Although, the main vector of dengue virus, Ae. aegypti, was not detected in Iran, other possible important vectors such as Ae. Albopictus and Ae. unilineatus were recorded (Doosti et al., 2016; Yaghoobi-Ershadi et al., 2017). West Nile virus (WNV), a member of the genus Flaviviruses, is one of the most widespread arboviruses (Chancey et al., 2015). The epidemiological evidence of WNV in different hosts in Iran was found (Bagheri et al., 2015), and the circulation of WNV in the main vector, Culex pipiens s.l. and Cx. pipiens, has been proved (Shahhosseini et al., 2017). Due to limited information on the situation of CHIKV, DENV and WNV in Iran, we performed a wide geographical investigation to determine the prevalence of IgG specific antibodies in human samples as well as the genome of WNV, CHIKV and DENV in mosquitoes.
2022, 37(1): 153-155.
doi: 10.1016/j.virs.2022.01.009
收稿日期: 2021-10-25
录用日期: 2022-01-10
出版日期: 2022-02-11
The rapid spread of SARS-CoV-2 has significantly impacted the worldwide health system. The SARS-CoV-2 currently bears a remarkably low genetic diversity even though it carries one of the largest RNA genomes among viruses (Rausch et al., 2020). However, the coronaviruses harbor the capability of undergoing recombination at a high rate which can lead to the emergence of novel viral derivatives (Rausch et al., 2020; Gribble et al., 2021). This in turn requires not only global surveillance of SARS-CoV-2 genome in various countries but also careful scrutiny in animal genomic reservoirs. Conventionally, RNA viruses evolve with a high mutation rate, however, the presence of ExoN ribonuclease in SARS-CoV-2 genome has made its case different from other viral species (Gribble et al., 2021). The variables of natural selection which potentially drift the SARS-CoV-2 evolutionary dynamics can be recorded by analyzing deposited sequence genomes for its fitness, transmissibility potential, and pathogenicity (Rouchka et al., 2020). This can potentially provide a way to draw a holistic picture at a national level, while simultaneously providing a comparative overview with worldwide sequences.
37卷第1期 (2022年2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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