Science

Innocent bystander mechanism behind hepatocyte injury in HCV/HIV coinfection

Last Updated: 2003-10-31 14:56:03 -0400 (Reuters Health)

By Will Boggs, MD

NEW YORK (Reuters Health) - Hepatic injury in hepatitis C virus (HCV) and HIV coinfection may not result from viral infection per se, according to a report in the October 15th issue of The Journal of Infectious Diseases.

"We hypothesized that hepatocytes exposed to HIV and HCV virions might be subjected to signaling effects produced by the binding of virus proteins to the cell surface, independent of cell infection and viral replication within the cell," the authors explain.

To test this hypothesis, Dr. Jerome E. Groopman and colleagues from Harvard Institutes of Medicine and Beth Israel Deaconess Medical Center in Boston, Massachusetts, developed an in vitro model of HCV/HIV coinfection using nanomolar concentrations of HCV E2 and HIV gp120 proteins.

HCV E2 and HIV gp120 bound to the surface of HepG2 cells and primary hepatocytes and induced apoptosis at concentrations well within the ranges seen during clinical infection, the authors report. The apoptotic effects seen with both proteins were synergistic rather than simply additive.

Blocking the CXCR4 surface receptor reduced apoptosis by about 42%, the report indicates, confirming the role of CXCR4 in the signaling effects leading to apoptosis.

Treatment of cells with the two viral proteins induced the expression of the pro-apoptotic Fas ligand and induced dephosphorylation and modest degradation of the anti-apoptotic AKT protein, the researchers note.

"Here, we provide evidence that suggests that HCV and HIV envelope proteins, at physiological concentrations, can have deleterious effects on hepatocytes via a unique pathway of collaborative signaling," the authors conclude.

"Therapeutic strategies designed to protect 'innocent bystander' hepatocytes from the cooperative effects of HIV and HCV binding may serve to limit the progressive liver disease seen in persons coinfected with HIV and HCV," the investigators add.

J Infect Dis 2003;188:1192-1204.