Researchers Uncover Clues to How HIV Promotes Hepatitis C Virus Replication

This photograph is an electronmicroscopic image of hepatitis c virus particles.

In a laboratory study described in the March 2008 issue of Gastroenterology, researchers at Massachusetts General Hospital and Harvard Medical School shed light on a potential mechanism underlying this phenomenon. As background, the authors noted that it has so far been unclear how HIV -- which does not target hepatocytes - is able to accelerate liver disease progression in people with HCV.

In the present analysis, the investigators assessed whether circulating HIV or specific HIV proteins might contribute to HCV pathogenesis through engagement of co-receptors on hepatocytes.

Results

• Inactivated HIV and the HIV gp120 envelope glycoprotein were associated with increased HCV replication in both a replicon and an infectious model of hepatitis C.

• HCV-regulated transforming growth factor-beta-1 (TGF-beta-1) expression was enhanced in the presence of HIV and gp120.

• Conversely, TGF-beta-1 also enhanced HCV replication.

• The promoter effect of HIV and gp120 on HCV replication was neutralized by antibodies to the CCR5 or CXCR4 co-receptors, which HIV uses to enter cells.

• 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.

• The effect of HIV on HCV replication was blocked by a neutralizing antibody to TGF-beta-1, indicating that the promoter effect is TGF-beta-1 dependent.