Reuters Health Information (2004-06-18): GB virus C inhibits replication of HIV-1
GB virus C inhibits replication of HIV-1
Last Updated: 2004-06-18 16:10:06 -0400 (Reuters Health)
NEW YORK (Reuters Health) - GB virus C (GBV-C) inhibits HIV-1 replication in cultured peripheral-blood mononuclear cells (PBMC) by increasing the production of HIV-inhibitory chemokines and decreasing the concentration of the HIV cell-surface co-receptor, CCR5, researchers report in the June 19th issue of The Lancet.
"Demonstrating an inhibitory effect of GBV-C on HIV in vitro provides one potential mechanism by which GBV-C could prolong survival in HIV-positive people," investigator Dr. Jack T. Stapleton told Reuters Health. "Thus, this study strengthens the clinical findings, and makes the case for a causal role for GBV-C in prolonged survival."
Until now, the mechanism by which GBV-C, a nonpathogenic cousin of hepatitis C virus, might influence HIV infection has not been clarified, Dr. Stapleton and colleagues from the University of Iowa in Iowa City point out.
The researchers infected PBMC with GBV-C and HIV-1 and compared them to cells infected with HIV-1 only. The presence of GBV-C was associated with "decreased replication of both clinical and laboratory HIV strains" that use either of the chemokine receptors CCR5 or CXCR4 for viral entry. Inhibition of HIV-1 replication by GBV-C was related to both the dose and timing of GBV-C infection.
GBV-C infection boosted expression of mRNA for RANTES and the macrophage inflammatory proteins (MIP-1alpha and MIP-1beta) -- the natural ligands for CCR5, and stromal-derived factor-1 -- the natural ligand for CXCR4. GBV-C infection also led to decreased expression of cell-surface CCR5.
The next step, Dr. Stapleton added, is to determine which aspect of GB virus triggers these changes in the cell. "This may allow the design of novel targets for drugs against HIV. Because these effects are at the cellular level, and are not directly targeting the virus, it will be more difficult for HIV to become resistant to the effects."