HPV virions hitchhike a ride on retromer complexes.
HPV virions hitchhike a ride on retromer complexes.
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HPV 病毒粒子搭乘逆转录酶复合体的便车。
DOI：
10.1073/pnas.1305245110
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发表时间：
2013
影响因子：
11.1
通讯作者：
Sapp,MartinJ
中科院分区：
文献类型：
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作者：
Sapp,MartinJ
无包膜病毒利用细胞途径进入并穿过宿主细胞的细胞质。事实上，许多目前已确定的途径已在病毒进入研究过程中初步确定。在 PNAS 中，利波夫斯基等人。通过证明人乳头瘤病毒 (HPV) 劫持逆转录酶复合物，将其从早期内体运输到跨高尔基体网络 (TGN)，将病毒利用的运输途径添加到不断增加的列表中 (1)。 HPV 是重要的人类病原体，感染皮肤和粘膜来源的上皮细胞，并依赖于这种分层上皮的终末分化程序来完成其生命周期。这些病毒通常会诱发良性自限性病变，即所谓的乳头状瘤（疣）和尖锐湿疣（生殖器疣），但也与癌症（如宫颈癌、肛门生殖器癌和口腔癌）有因果关系。总共 5% 以上的人类癌症与 HPV 相关 (2)。 HPV 是无包膜病毒，由主要衣壳蛋白 L1、次要衣壳蛋白 L2 和闭环双链 DNA 基因组组成。与其他无包膜病毒一样，HPV 病毒粒子极其稳定，可以耐受高温、低 pH、蛋白酶和干燥等侵害。因此，乳头瘤病毒已经进化出通过在附着于宿主细胞后发生构象变化来破坏衣壳脱衣的稳定性的策略。 L1 介导的病毒与硫酸乙酰肝素蛋白聚糖的结合会诱导 L2 蛋白隐藏的氨基末端部分的暴露，这是由宿主细胞伴侣亲环蛋白 B 促进的 (3-5)。暴露的 L2 随后被弗林蛋白酶转化酶裂解 (6)。这些过程导致对主要附着受体的亲和力丧失，转移至可能存在于富含四跨膜的微域中或与之相关的难以捉摸的摄取受体，并且对于随后在内吞室中脱壳至关重要 (7)。病毒颗粒通过最近描述的称为“微胞饮作用”的途径内化，该途径需要受体信号传导和肌动蛋白细胞骨架
Nonenveloped viruses use cellular pathways to gain access to and traverse the cytoplasm of host cells. Indeed, many of the by now well-established pathways have been initially identified during the study of virus entry. In PNAS, Lipovsky et al. add to the growing list of transport pathways exploited by viruses by demonstrating that human papillomaviruses (HPV) hijack the retromer complex for trafficking from early endosomes to the trans-Golgi network (TGN)(1). HPV are important human pathogens that infect epithelial cells of skin and mucosal origins and depend on the terminal differentiation program of this stratified epithelium for completion of their lifecycles. These viruses commonly induce benign self-limiting lesions, so called papillomas (warts) and condylomas (genital warts), but are also causally linked to carcinomas, such as cervical, anogenital, and oral cancers. In total, HPV are associated with more than 5% of all human cancers (2). HPV are nonenveloped viruses that are composed of the major capsid protein, L1, the minor capsid protein, L2, and a closed circular double-stranded DNA genome. Like other nonenveloped viruses, HPV virions are extremely stable and tolerate insults, such as high temperature, low pH, proteases, and desiccation. Papillomaviruses have thus evolved strategies to destabilize the capsid for uncoating by undergoing conformational changes following attachment to host cells. The L1-mediated virus binding to heparan sulfate proteoglycans induces exposure of the otherwise hidden amino terminal portion of the L2 protein, which is facilitated by the host cell chaperone cyclophilin B (3–5). The exposed L2 is subsequently cleaved by a furin convertase (6). These processes result in loss of affinity to the primary attachment receptor, transfer to an elusive uptake receptor that probably resides in or is associated with tetraspaninenriched microdomains, and are essential for subsequent uncoating in the endocytic compartment (7). Viral particles are internalized via a recently described pathway termed “micropinocytosis,” which requires receptor signaling and actin cytoskeleton