Human Papillomavirus Type 16 Infection of Human Keratinocytes Requires Clathrin and Caveolin-1 and Is Brefeldin A Sensitive
Human Papillomavirus Type 16 Infection of Human Keratinocytes Requires Clathrin and Caveolin-1 and Is Brefeldin A Sensitive
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DOI：
10.1128/jvi.00576-09
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发表时间：
2009-08-15
影响因子：
5.4
通讯作者：
Meneses, Patricio I.
中科院分区：
文献类型：
--
作者：
Laniosz, Valerie;Dabydeen, Sarah A.;Meneses, Patricio I.
人乳头瘤病毒16型（HPV 16）已被确定为导致宫颈癌的最常见病原体。尽管对HPV 16在肿瘤发生中的作用有了清楚的了解，但对HPV 16在感染期间如何运输的细节了解甚少。HPV 16已被确定通过网格蛋白介导的内吞作用进入，但HPV 16感染的后续步骤仍不清楚。有新的证据表明，几种病毒利用了内吞途径之间的串扰。具体而言，JCV和牛乳头瘤病毒1型已被证明通过网格蛋白依赖性内吞作用进入细胞，然后需要小窝蛋白-1介导的运输进行感染。在本文中，我们表明，HPV 16依赖于小窝蛋白-1网格蛋白介导的内吞作用后。我们首次提供了HPV 16感染依赖于运输到内质网（ER）的证据。这种新的运输可能解释了HPV 16感染中对小窝途径的需求，因为网格蛋白介导的内吞作用通常不会导致ER。我们的数据表明HPV 16在网格蛋白介导的进入后的感染途径是依赖于小窝蛋白-1和COPI的。对HPV 16分选和运输所涉及的步骤的理解开辟了开发新方法来干扰HPV 16感染和减少包括宫颈癌在内的乳头状瘤病毒疾病负担的可能性。
Human papillomavirus type 16 (HPV16) has been identified as being the most common etiological agent leading to cervical cancer. Despite having a clear understanding of the role of HPV16 in oncogenesis, details of how HPV16 traffics during infection are poorly understood. HPV16 has been determined to enter via clathrin-mediated endocytosis, but the subsequent steps of HPV16 infection remain unclear. There is emerging evidence that several viruses take advantage of cross talk between routes of endocytosis. Specifically, JCV and bovine papillomavirus type 1 have been shown to enter cells by clathrin-dependent endocytosis and then require caveolin-1-mediated trafficking for infection. In this paper, we show that HPV16 is dependent on caveolin-1 after clathrin-mediated endocytosis. We provide evidence for the first time that HPV16 infection is dependent on trafficking to the endoplasmic reticulum (ER). This novel trafficking may explain the requirement for the caveolar pathway in HPV16 infection because clathrin-mediated endocytosis typically does not lead to the ER. Our data indicate that the infectious route for HPV16 following clathrin-mediated entry is caveolin-1 and COPI dependent. An understanding of the steps involved in HPV16 sorting and trafficking opens up the possibility of developing novel approaches to interfere with HPV16 infection and reduce the burden of papillomavirus diseases including cervical cancer.