A recombinant vesicular stomatitis virus encoding HIV-1 receptors and human OX40 ligand efficiently eliminates HIV-1-infected CD4-positive T cells expressing OX40.

Abstract OX40 protein is highly expressed on activated CD4-positive T cells that are susceptible for human immunodeficiency virus type 1 (HIV-1) infection. To target and kill HIV-1–infected OX40 + T cells, we used a recombinant vesicular stomatitis virus (rVSV) lacking its envelope glycoprotein ( Δ G) and instead expressing HIV-1 receptors CD4/CXCR4 and OX40 ligand (OX40L). Expression of OX40L as well as HIV-1 receptors on the VSV particles led to specific infection of OX40 + T cells, including primary cells, either acutely or chronically infected with X4 HIV-1. Consequently, the rVSV rapidly eliminated these infected cells and caused a marked reduction of HIV-1 viral load in culture. Inclusion of the OX40L gene in the VSV recombinant led to significantly better infection and HIV-1 elimination compared with an rVSVΔG expressing only HIV-1 receptors. A novel rVSVΔG encoding both HIV-1 receptors and OX40L has a potentially greater therapeutic value than an rVSVΔG expressing only HIV-1 receptors.