HIV Research Today is a free monthly online journal that collates and summarizes the latest research about HIV, including details on human immunodeficiency virus, testing, treatment, prevention, vaccines, aids.

HIV increases HCV replication in a TGF-beta1-dependent manner.

Lin W, Weinberg EM, Tai AW, Peng LF, Brockman MA, Kim KA, Kim SS, Borges CB, Shao RX, Chung RT

Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

BACKGROUND & AIMS: Human immunodeficiency virus (HIV) coinfection increases hepatitis C virus (HCV)-related progression of hepatic fibrosis, increases HCV persistence, and decreases response rates to interferon-based anti-HCV therapy. It has remained unclear how HIV, a nonhepatotropic virus, accelerates the progression of liver disease by HCV. METHODS: We explored the possibility that circulating HIV and/or its proteins contribute to the pathogenesis of HCV through engagement of extracellular coreceptors on hepatocytes. RESULTS: In this study, we found that inactivated HIV or gp120 increases HCV replication and enhances HCV-regulated transforming growth factor (TGF)-beta1 expression in both a replicon and an infectious model of HCV. This proviral effect of HIV and gp120 on HCV replication is neutralized by antibodies to CCR5 or CXCR4. However, HIV and gp120 did not alter type I interferon-mediated signaling in these HCV models, indicating that HIV regulates HCV replication through an alternative mechanism. Interestingly, we found that human TGF-beta1 also enhanced HCV replication. The effect of HIV on HCV replication was blocked by a neutralizing antibody to TGF-beta1, indicating that its effects on HCV replication are TGF-beta1 dependent. CONCLUSIONS: These results suggest a novel mechanism by which HIV not only enhances HCV replication but also contributes to progression of hepatic fibrosis.

Published 7 March 2008 in Gastroenterology, 134(3): 803-11.
Full-text of this article is available online (may require subscription).

© 2004-2008 HIV Research Today. All Rights Reserved.