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.
Schnell
M J
MJ
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Johnson
J E
JE
Buonocore
L
L
Rose
J K
JK
D000818:Animals; D015704:CD4 Antigens / Q000235:genetics; D006224:Cricetinae; D019204:GTP-Binding Proteins / Q000235:genetics; D017353:Gene Deletion; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D006023:Glycoproteins / Q000235:genetics; D015658:HIV Infections / Q000628:therapy* / Q000821:virology*; D015497:HIV-1 / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells / Q000821:virology; D007668:Kidney / Q000166:cytology; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics; D016253:Microscopy, Immunoelectron; D016296:Mutagenesis / Q000502:physiology; D019718:Receptors, CXCR4; D015728:Receptors, HIV / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014721:Vesicular stomatitis Indiana virus / Q000254:growth & development / Q000502:physiology* / Q000648:ultrastructure; D014759:Viral Envelope Proteins / Q000235:genetics / Q000502:physiology; D014779:Virus Replication
D015704:CD4 Antigens; C028391:G protein, vesicular stomatitis virus; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019718:Receptors, CXCR4; D015728:Receptors, HIV; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D019204:GTP-Binding Proteins