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Journal of Virology, January 2007, p. 374-383, Vol. 81, No. 1
0022-538X/07/$08.00+0     doi:10.1128/JVI.01134-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Initiation of Hepatitis C Virus Infection Is Dependent on Cholesterol and Cooperativity between CD81 and Scavenger Receptor B Type I{triangledown} ,{dagger}

Sharookh B. Kapadia,1 Heidi Barth,2 Thomas Baumert,2 Jane A. McKeating,3 and Francis V. Chisari1*

Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037,1 Department of Medicine II, University of Freiburg, Freiburg, Germany,2 Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom3

Received 1 June 2006/ Accepted 5 October 2006

In the past several years, a number of cellular proteins have been identified as candidate entry receptors for hepatitis C virus (HCV) by using surrogate models of HCV infection. Among these, the tetraspanin CD81 and scavenger receptor B type I (SR-BI), both of which localize to specialized plasma membrane domains enriched in cholesterol, have been suggested to be key players in HCV entry. In the current study, we used a recently developed in vitro HCV infection system to demonstrate that both CD81 and SR-BI are required for authentic HCV infection in vitro, that they function cooperatively to initiate HCV infection, and that CD81-mediated HCV entry is, in part, dependent on membrane cholesterol.

* Corresponding author. Mailing address: The Scripps Research Institute, Department of Molecular and Experimental Medicine, 10550 North Torrey Pines Road, La Jolla, CA 92037. Phone: (858) 784-8228. Fax: (858) 784-2160. E-mail: fchisari{at}scripps.edu.

{triangledown} Published ahead of print on 18 October 2006.

{dagger} This is manuscript number 18188-MEM from The Scripps Research Institute.

Journal of Virology, January 2007, p. 374-383, Vol. 81, No. 1
0022-538X/07/$08.00+0     doi:10.1128/JVI.01134-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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