NS5A Peptide Derived from Hepatitis C Virus Exhibits Antiviral Activity against HIV

One piece of a hepatitis C virus (HCV) protein exhibits antiviral activity against HIV as well as HCV, according to a study published in the April 8, 2008 Proceedings of the National Academy of Science USA.

Researchers from the Scripps Research Institute in La Jolla, California, and from the Netherlands discovered that a specific peptide derived from a non-structural HCV protein has potent antiviral activity against HIV.

The peptide -- dubbed C5A -- is an amphipathic alpha-helical peptide derived from the HCV NS5A anchor domain. It was already known to have antiviral activity against HCV itself, but its activity against HIV had not previously been reported.

The C5A peptide exhibited a broad range of antiviral activity against HIV isolates in laboratory cell cultures, the investigators wrote, and it prevented infection of 3 types of cells targeted by HIV: CD4 T-cells, macrophages, and dendritic cells.

The authors added that C5A appeared to exert its activity by "disrupting the integrity of the viral membrane and capsid core" (part of the internal structure of HIV), while preserving the integrity of host cell membranes.

The laboratory studies showed that C5A can interrupt ongoing CD4 cell infection and can prevent "transmigration" of HIV through genital epithelial cells, infection of types of mucosal cells targeted by the virus, and the transfer from of HIV from dendritic cells (among the first to be infected during mucosal transmission) to CD4 cells.

The investigators concluded that these findings justify future experiments to determine whether C5A can safely prevent HIV transmission in animals and eventually humans. C5A's mechanism of action suggests that it might be useful as a microbicide to prevent transmission during sex.

The present study did not address whether the presence of HCV's C5A peptide might have a suppressive effect on HIV in HIV-HCV coinfected individuals. Studies to date indicate that coinfection with HIV tends to accelerate HCV-related liver disease progression. Data are mixed concerning the effect of HCV on HIV disease, with some researchers finding worse disease progression and some finding no difference. However, there is no evidence from patients showing that HCV coinfection in any way slows or ameliorates HIV disease progression.

5/09/08

Reference
MD Bobart, G Cheng, L de Witte, and others. Hepatitis C virus NS5A anchor peptide disrupts human immunodeficiency virus. Proceedings of the National Academy of Science USA 105(14): 5525-5530. April 8, 2008.