Construction of a Novel Virus That Targets HIV-1-Infected Cells and Controls HIV-1 Infection

We describe a recombinant vesicular stomatitis virus lacking its glycoprotein gene and expressing instead the HIV-1 receptor CD4 and a coreceptor, CXCR4. This virus was unable to infect normal cells but did infect, propagate on, and kill cells that were first infected with HIV-1 and therefore had the HIV membrane fusion protein on their surface. Killing of HIV-1-infected cells controlled HIV infection in a T cell line and reduced titers of infectious HIV-1 in the culture by as much as 10(4)-fold. Such a targeted virus could have therapeutic value in reducing HIV viral load. Our results also demonstrate a general strategy of targeting one virus to the envelope protein of another virus to control infection.