Cruz Linda, Biryukov Jennifer, Conway Michael J, Meyers Craig
Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Viruses. 2015 Nov 11;7(11):5813-30. doi: 10.3390/v7112910.
Infections by high-risk human papillomaviruses (HPV) are the causative agents for the development of cervical cancer. As with other non-enveloped viruses, HPVs are taken up by the cell through endocytosis following primary attachment to the host cell. Through studies using recombinant pseudovirus particles (PsV), many host cellular proteins have been implicated in the process. The proprotein convertase furin has been demonstrated to cleave the minor capsid protein, L2, post-attachment to host cells and is required for infectious entry by HPV16 PsV. In contrast, using biochemical inhibition by a furin inhibitor and furin-negative cells, we show that tissue-derived HPV16 native virus (NV) initiates infection independent of cellular furin. We show that HPV16 L2 is cleaved during virion morphogenesis in differentiated tissue. In addition, HPV45 is also not dependent on cellular furin, but two other alpha papillomaviruses, HPV18 and HPV31, are dependent on the activity of cellular furin for infection.
高危型人乳头瘤病毒（HPV）感染是宫颈癌发生的致病因素。与其他无包膜病毒一样，HPV在初次附着于宿主细胞后通过内吞作用被细胞摄取。通过使用重组假病毒颗粒（PsV）进行的研究，许多宿主细胞蛋白参与了这一过程。已证明前蛋白转化酶弗林蛋白酶在附着于宿主细胞后可切割次要衣壳蛋白L2，并且是HPV16 PsV感染性进入所必需的。相比之下，通过使用弗林蛋白酶抑制剂的生化抑制作用和弗林蛋白酶阴性细胞，我们发现组织来源的HPV16天然病毒（NV）独立于细胞弗林蛋白酶引发感染。我们表明HPV16 L2在分化组织的病毒体形态发生过程中被切割。此外，HPV45也不依赖于细胞弗林蛋白酶，但另外两种α乳头瘤病毒HPV18和HPV31的感染依赖于细胞弗林蛋白酶的活性。
