Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
CD4 Antigens / genetics
-
Cricetinae
-
GTP-Binding Proteins / genetics
-
Gene Deletion
-
Gene Expression Regulation, Viral / physiology
-
Glycoproteins / genetics
-
HIV Infections / therapy*
-
HIV Infections / virology*
-
HIV-1 / growth & development
-
HIV-1 / physiology*
-
Humans
-
Jurkat Cells / virology
-
Kidney / cytology
-
Membrane Glycoproteins*
-
Membrane Proteins / genetics
-
Microscopy, Immunoelectron
-
Mutagenesis / physiology
-
Receptors, CXCR4
-
Receptors, HIV / genetics
-
Recombinant Fusion Proteins / physiology
-
Vesicular stomatitis Indiana virus / growth & development
-
Vesicular stomatitis Indiana virus / physiology*
-
Vesicular stomatitis Indiana virus / ultrastructure
-
Viral Envelope Proteins / genetics
-
Viral Envelope Proteins / physiology
-
Virus Replication
Substances
-
CD4 Antigens
-
G protein, vesicular stomatitis virus
-
Glycoproteins
-
Membrane Glycoproteins
-
Membrane Proteins
-
Receptors, CXCR4
-
Receptors, HIV
-
Recombinant Fusion Proteins
-
Viral Envelope Proteins
-
GTP-Binding Proteins