A pathogenic picornavirus acquires an envelope by hijacking cellular membranes.
A pathogenic picornavirus acquires an envelope by hijacking cellular membranes.
复制标题
DOI：
10.1038/nature12029
复制
发表时间：
2013-04-18
期刊：
影响因子：
64.8
通讯作者：
Lemon SM
中科院分区：
文献类型：
--
作者：
Feng Z;Hensley L;McKnight KL;Hu F;Madden V;Ping L;Jeong SH;Walker C;Lanford RE;Lemon SM
动物病毒在结构上根据是否存在由脂质双层膜组成的包膜进行广泛分类，这些属性深刻影响稳定性，传播和免疫识别。在那些缺乏包膜的病毒中，小核糖核酸病毒科是一个庞大而多样的正链RNA病毒家族，其中包括甲型肝炎病毒（HAV），这是一种古老的人类病原体，仍然是肠道传播肝炎的常见原因。HAV以类似隐形的方式感染，并在肝脏中有效复制。病毒特异性抗体仅在感染3-4周后出现，通常预示着感染的消退。尽管机制上无法解释，但抗HAV抗体和灭活全病毒疫苗在暴露后2周内接种时均可预防疾病，此时病毒在肝脏中复制良好。在这里，我们表明，从细胞释放的HAV是隐藏在宿主衍生的膜，从而保护病毒粒子从抗体介导的中和。这些包膜病毒（“eHAV”）类似于外泌体，即越来越多地被认为在细胞间通讯中发挥重要作用的小囊泡。它们是完全传染性的，对氯仿提取物敏感，并在受感染的人的血液中循环。它们的生物发生依赖于与转运所需的内体分选复合物（ESCRT）、VPS 4 B和阿利克斯相关的宿主蛋白。虽然HAV对膜的劫持促进了中和抗体的逃逸，并可能促进病毒在肝脏内的传播，但抗衣壳抗体限制了eHAV感染后的复制，这表明了暴露后预防的可能解释。HAV的膜劫持模糊了“包膜”和“无包膜”病毒之间的经典区别，并对病毒从感染细胞中排出的机制以及宿主免疫应答具有广泛的影响。
Animal viruses are broadly categorized structurally by the presence or absence of an envelope composed of a lipid-bilayer membrane, attributes that profoundly affect stability, transmission, and immune recognition. Among those lacking an envelope, the Picornaviridae are a large and diverse family of positive-strand RNA viruses that includes hepatitis A virus (HAV), an ancient human pathogen that remains a common cause of enterically-transmitted hepatitis. HAV infects in a stealth-like manner and replicates efficiently in the liver. Virus-specific antibodies appear only after 3–4 weeks of infection, and typically herald its resolution. Although unexplained mechanistically, both anti-HAV antibody and inactivated whole-virus vaccines prevent disease when administered as late as 2 weeks after exposure, when virus replication is well established in the liver. Here, we show that HAV released from cells is cloaked in host-derived membranes, thereby protecting the virion from antibody-mediated neutralization. These enveloped viruses (“eHAV”) resemble exosomes, small vesicles that are increasingly recognized to play important roles in intercellular communications. They are fully infectious, sensitive to chloroform extraction, and circulate in the blood of infected humans. Their biogenesis is dependent upon host proteins associated with endosomal-sorting complexes required for transport (ESCRT), VPS4B and ALIX. While the hijacking of membranes by HAV facilitates escape from neutralizing antibodies and likely promotes virus spread within the liver, anti-capsid antibodies restrict replication following infection with eHAV, suggesting a possible explanation for post-exposure prophylaxis. Membrane hijacking by HAV blurs the classic distinction between “enveloped” and “nonenveloped” viruses, and has broad implications for mechanisms of viral egress from infected cells as well as host immune responses.
登录
查看更多内容
影响因子：
3.1
作者：
SHIMIZU, YK;SHIKATA, T;TANIKAWA, K
通讯作者：
TANIKAWA, K
影响因子：
6.4
作者：
TAYLOR, KL;MURPHY, PC;LEMON, SM
通讯作者：
LEMON, SM
影响因子：
3.7
作者：
JANSEN, RW;NEWBOLD, JE;LEMON, SM
通讯作者：
LEMON, SM
影响因子：
5.4
作者：
LEMON, SM;MURPHY, PC;JANSEN, RW
通讯作者：
JANSEN, RW
影响因子：
5.4
作者：
Feigelstock, D;Thompson, P;Kaplan, GG
通讯作者：
Kaplan, GG