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Journal article

Hepatitis B virus requires intact caveolin-1 function for productive infection in HepaRG cells.

Abstract:
Investigation of the entry pathways of hepatitis B virus (HBV), a member of the family Hepadnaviridae, has been hampered by the lack of versatile in vitro infectivity models. Most concepts of hepadnaviral infection come from the more robust duck HBV system; however, whether the two viruses use the same mechanisms to invade target cells is still a matter of controversy. In this study, we investigate the role of an important plasma membrane component, caveolin-1 (Cav-1), in HBV infection. Caveolins are the main structural components of caveolae, plasma membrane microdomains enriched in cholesterol and sphingolipids, which are involved in the endocytosis of numerous ligands and complex signaling pathways within the cell. We used the HepaRG cell line permissive for HBV infection to stably express dominant-negative Cav-1 and dynamin-2, a GTPase involved in vesicle formation at the plasma membrane and other organelles. The endocytic properties of the newly established cell lines, designated HepaRG(Cav-1), HepaRG(Cav-1Delta1-81), HepaRG(Dyn-2), and HepaRG(Dyn-2K44A), were validated using specific markers for different entry routes. The cells maintained their properties during cell culture, supported differentiation, and were permissive for HBV infection. The levels of both HBV transcripts and antigens were significantly decreased in cells expressing the mutant proteins, while viral replication was not directly affected. Chemical inhibitors that specifically inhibit clathrin-mediated endocytosis had no effect on HBV infection. We concluded that HBV requires a Cav-1-mediated entry pathway to initiate productive infection in HepaRG cells.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1128/jvi.01207-09

Authors


Publisher:
American Society for Microbiology
Journal:
Journal of virology More from this journal
Volume:
84
Issue:
1
Pages:
243-253
Publication date:
2010-01-01
DOI:
EISSN:
1098-5514
ISSN:
0022-538X


Language:
English
Keywords:
Pubs id:
pubs:99860
UUID:
uuid:a8319a85-6585-496a-b9d0-989b138e00fd
Local pid:
pubs:99860
Source identifiers:
99860
Deposit date:
2012-12-19
ARK identifier:

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