T Lymphocytes transduced with a lentiviral vector expressing F12-Vif are protected from HIV-1 infection in an APOBEC3G-independent manner.
The viral infectivity factor (Vif) is an essential component of the HIV-1 infectious cycle. Vif counteracts the action of the cytidine deaminase APOBEC3G (AP3G), which confers nonimmune antiviral defense against HIV-1 to T lymphocytes. Disabling or interfering with the function of Vif could represent an alternative therapeutic approach to AIDS. We have expressed a natural mutant of Vif, F12-Vif, in a VSV-G-pseudotyped lentiviral vector under the Tat-inducible control of the HIV-1 LTR. Conditional expression of F12-Vif prevents replication and spreading of both CXCR4 and CCR5 strains of HIV-1 in human primary T lymphocyte and T cell lines. T cells transduced with F12-Vif release few HIV-1 virions and with reduced infectivity. Several lines of evidence indicate that HIV-1 interference requires the presence of both wild-type and F12-Vif proteins, suggesting a dominant-negative feature of the F12-Vif mutant. Surprisingly, however, the F12-Vif-mediated inhibition does not depend on the reestablishment of the AP3G function.
Vallanti
Giuliana
G
Molmed SpA, Milan, Italy.
Lupo
Rossella
R
Federico
Maurizio
M
Mavilio
Fulvio
F
Bovolenta
Chiara
C
D000071480:APOBEC-3G Deaminase; D000595:Amino Acid Sequence; D002460:Cell Line; D003564:Cytidine Deaminase; D016346:Gene Products, vif / Q000096:biosynthesis / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008969:Molecular Sequence Data; D009700:Nucleoside Deaminases; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D012097:Repressor Proteins; D013601:T-Lymphocytes / Q000166:cytology / Q000821:virology*; D014161:Transduction, Genetic; D014771:Virion / Q000378:metabolism; D054320:vif Gene Products, Human Immunodeficiency Virus
D016346:Gene Products, vif; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D012097:Repressor Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase