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Journal of Virology, October 2003, p. 10432-10436, Vol. 77, No. 19
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.19.10432-10436.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Antiviral Treatment Down-Regulates Peripheral B-Cell CD81 Expression and CD5 Expansion in Chronic Hepatitis C Virus Infection

Eli Zuckerman,1* Aharon Kessel,2 Gleb Slobodin,1 Edmond Sabo,3 Daniel Yeshurun,1 and Elias Toubi2

Liver Unit, Department of Internal Medicine A,1 Institute of Clinical Immunology, Bnai Zion Medical Center,2 Department of Pathology, Carmel Medical Center, Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel3

Received 17 January 2003/ Accepted 9 July 2003

Hepatitis C virus (HCV) infection is associated with immune-mediated abnormalities and B-cell lymphoproliferation. Recently, CD81 was identified as an HCV receptor on B lymphocytes, providing a mechanism by which B cells are infected and activated by the virus. It has recently been shown that peripheral B-cell CD81 overexpression and CD5+ subpopulation expansion correlate with HCV viral load and are associated with the development of HCV-related autoimmunity. In the present study, we assessed the effects of combination antiviral therapy (alfa interferon and ribavirin) on peripheral B-cell CD81 expression and CD5 expansion and the presence of autoimmune markers. Peripheral B-cell CD5 expression and the mean fluorescence intensity of CD81 were assessed by flow cytometry before and after treatment in 15 HCV-infected patients, in 10 untreated patients, and in 25 healthy controls. A significant posttreatment decrease in peripheral B-cell CD81 expression and disappearance of CD5+ B-cell expansion were observed in all nine patients in whom a complete and sustained virological response was achieved (P < 0.01) (comparable to those for healthy controls). The decrease in CD81 overexpression and CD5 expansion in these patients was associated with a decrease and/or disappearance of autoimmune markers. In contrast, in nonresponders overexpression of CD81 and expansion of the CD5+ B-cell subpopulation were not significantly changed and were comparable to those for untreated patients. In conclusion, antiviral therapy down-regulates peripheral B-cell CD81 expression and the CD5+ population, either directly or by its effect on HCV RNA load. The overexpression of CD81 and the expansion of the population of CD5+ peripheral B cells in HCV-infected patients may possibly play a role in the development of HCV-associated autoimmunity and lymphoproliferation.

* Liver Unit, Department of Internal Medicine A, Bnai Zion Medical Center, 47 Golomb St., P.O. Box 4940, Haifa 31048 Israel. Phone: 972-4-8359779. Fax: 972-4-8359790. E-mail: zuckerman{at}b-zion.org.il.

Journal of Virology, October 2003, p. 10432-10436, Vol. 77, No. 19
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.19.10432-10436.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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