2012 Fiscal Year Final Research Report
Identification of a host protein that is necessary for the initial stage of HPV infection
| Project/Area Number |
22590425
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
ISHII Yoshiyuki 国立感染症研究所, 病原体ゲノム解析研究センター, 主任研究官 (90342899)
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| Project Period (FY) |
2010 – 2012
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| Keywords | HPV / L2 / TRAPP複合体 / TRAPPC8 / エンドサイトーシス |
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| Research Abstract |
The human papillomavirus (HPV) is a member of the papillomaviridae family of non-enveloped DNA tumor viruses. Differing from enveloped viruses, HPVs are thought to gain cell entry and escape into the cytoplasm using their own strategy. However, the cellular machinery required for the initial infection stage is poorly understood. Here we report that transport protein particle complex subunit 8 (TRAPPC8), a host protein that interacts with HPV minor capsid protein L2, plays a crucial role in the HPV entry process. TRAPPC8-knockdown epithelial cells showed reduced susceptibility to pseudovirus (PsV) transduction and authentic virus infection. TRAPPC8 was present in cytosolic and microsomal fractions of HeLa cells. The C-terminal region was exposed on the cell surface and co-localized with PsV after inoculation with PsV. The entry of PsV and L2-deficient PsV into TRAPPC8-knockdown cells was severely impaired, suggesting that TRAPPC8 plays an important role in HPV entry in a L2 interaction-independent manner. On the other hand, expression of GFP-fused L2s that can interact with TRAPPC8 induced dispersal of Golgi stack structure in HeLa cells, which is a phenotype observed by TRAPPC8 knockdown. These results imply a possibility that during viral intracellular trafficking L2 binding to TRAPPC8 inhibits its function and results in Golgi de-stabilization, which may help an escape of the HPV genome from the trans-Golgi network into the cytoplasm or nucleus after attaining cell entry.
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Research Products
(8 results)
