Characterization of a peptide domain within the GB virus C envelope glycoprotein (E2) that inhibits HIV replication

GB virus C (GBV-C) infection is associated with prolonged survival in HIV-infected cohorts, and GBV-C E2 protein inhibits HIV entry when added to CD4+ T cells. To further characterize E2 effects on HIV replication, stably transfected Jurkat cell lines expressing GBV-C E2 or control sequences were infected with HIV and replication was measured. HIV replication (all 6 isolates studied) was inhibited in all cell lines expressing a region of 17 amino acids of GBV-C E2, but not in cell lines expressing E2 without this region. In contrast, mumps and yellow fever virus replication was not inhibited by E2 protein expression. Synthetic GBV-C E2 17mer peptides did not inhibit HIV replication unless they were fused to a tat-protein-transduction-domain (TAT) for cellular uptake. These data identify the region of GBV-C E2 protein involved in HIV inhibition, and suggest that this GBV-C E2 peptide must gain entry into the cell to inhibit HIV.

► GBV-C E2 expression in a CD4+ T cell line inhibits HIV entry.
► Expression of 17 amino acids of GBV-C E2 protein inhibits HIV in a CD4+ T cell line.
► Cells expressing E2 inhibit HIV in bystander cells if there is cell-to-cell contact.
► Intracellular, but not extracellular E2 peptide inhibits HIV if it gains entry.