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Journal of Virology, February 2009, p. 2011-2014, Vol. 83, No. 4
0022-538X/09/$08.00+0     doi:10.1128/JVI.01888-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Tight Junction Proteins Claudin-1 and Occludin Control Hepatitis C Virus Entry and Are Downregulated during Infection To Prevent Superinfection {triangledown} ,§

Shufeng Liu,1,{dagger} Wei Yang,1,{dagger},{ddagger} Le Shen,2 Jerrold R. Turner,2 Carolyn B. Coyne,3 and Tianyi Wang1*

Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, Pennsylvania,1 Department of Pathology, The University of Chicago, Chicago, Illinois,2 Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, Pennsylvania 152613

Received 8 September 2008/ Accepted 19 November 2008

A tight junction (TJ) protein, claudin-1 (CLDN1), was identified recently as a key factor for hepatitis C virus (HCV) entry. Here, we show that another TJ protein, occludin, is also required for HCV entry. Mutational study of CLDN1 revealed that its tight junctional distribution plays an important role in mediating viral entry. Together, these data support the model in which HCV enters liver cells from the TJ. Interestingly, HCV infection of Huh-7 hepatoma cells downregulated the expression of CLDN1 and occludin, preventing superinfection. The altered TJ protein expression may contribute to the morphological and functional changes observed in HCV-infected hepatocytes.

* Corresponding author. Mailing address: Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, PA 15261. Phone: (412) 383-9916. Fax: (412) 383-8926. E-mail: tywang{at}pitt.edu

{triangledown} Published ahead of print on 3 December 2008.

§ Supplemental material for this article may be found at http://jvi.asm.org/.

{dagger} These authors contribute equally to the work.

{ddagger} Present address: Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University, 5 Dong Dan San Tiao, Beijing 100005, China.

Journal of Virology, February 2009, p. 2011-2014, Vol. 83, No. 4
0022-538X/09/$08.00+0     doi:10.1128/JVI.01888-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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