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Teaching new tricks to an old foe: murinizing hepatitis C virus
Center for the Study of Hepatitis C Laboratory of Virology and Infectious Diseases Rockefeller University, New York, NY. (Gisa Gerold)
2010 (English)In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 52, no 6, p. 2233-2236Article in journal (Refereed) Published
Abstract [en]

Hepatitis C virus (HCV) naturally infects only humans and chimpanzees. The determinants responsible for this narrow species tropism are not well defined. Virus cell entry involves human scavenger receptor class B type I (SR‐BI), CD81, claudin‐1 and occludin. Among these, at least CD81 and occludin are utilized in a highly species‐specific fashion, thus contributing to the narrow host range of HCV. We adapted HCV to mouse CD81 and identified three envelope glycoprotein mutations which together enhance infection of cells with mouse or other rodent receptors approximately 100‐fold. These mutations enhanced interaction with human CD81 and increased exposure of the binding site for CD81 on the surface of virus particles. These changes were accompanied by augmented susceptibility of adapted HCV to neutralization by E2‐specific antibodies indicative of major conformational changes of virus‐resident E1/E2‐complexes. Neutralization with CD81, SR‐BI‐ and claudin‐1‐specific antibodies and knock down of occludin expression by siRNAs indicate that the adapted virus remains dependent on these host factors but apparently utilizes CD81, SR‐BI and occludin with increased efficiency. Importantly, adapted E1/E2 complexes mediate HCV cell entry into mouse cells in the absence of human entry factors. These results further our knowledge of HCV receptor interactions and indicate that three glycoprotein mutations are sufficient to overcome the species‐specific restriction of HCV cell entry into mouse cells. Moreover, these findings should contribute to the development of an immunocompetent small animal model fully permissive to HCV.

Place, publisher, year, edition, pages
American Association for the Study of Liver Diseases , 2010. Vol. 52, no 6, p. 2233-2236
Identifiers
URN: urn:nbn:se:umu:diva-148170DOI: 10.1002/hep.24045PubMedID: 21105113OAI: oai:DiVA.org:umu-148170DiVA, id: diva2:1210810
Note

Bitzegeio J, Bankwitz D, Hueging K, Haid S, Brohm C, Zeisel MB, et al. Adaptation of hepatitis C virus to mouse CD81 permits infection of mouse cells in the absence of human entry factors. PLoS Pathog 2010;6:e1000978. (Reprinted with permission.)

Available from: 2018-05-29 Created: 2018-05-29 Last updated: 2019-01-31Bibliographically approved

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CiteExportLink to record
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Citation style
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