Nuclear localization of HIV type 1 Vif isolated from a long-term asymptomatic individual and potential role in virus attenuation.
Recent reports have determined that HIV-1 Vif counteracts an innate antiviral cellular factor, Apobec3G. However, the function of Vif during HIV-1 pathogenesis remains poorly understood. To gain a better understanding of Vif function, the viral isolate from an HIV-1-infected long-term nonprogressor (LTNP) that displayed a Vif-mutant replication phenotype was studied. This LTNP has been infected since before 1983 and has no HIV-related disease in the absence of antiretroviral therapy. From separate samples, obtained on more than one study visit, virus grew in cocultures of LTNP cells with Vif-complementing T cell lines, but not the parental T cell lines. An unusual amino acid motif (KKRK) was found in the Vif sequence at positions 90 to 93. Since this motif commonly functions as a nuclear localization sequence, experiments were performed to determine the ability of this KKRK motif to mediate nuclear localization of Vif. Wild-type Vif displayed a predominantly cytoplasmic distribution. In contrast, the KKRK Vif showed a predominantly nuclear localization. The effect of the KKRK mutation on virus production and infectivity was also studied. The KKRK motif that mislocalizes Vif to the nucleus also reduces viral replication and infectivity in nonpermissive cells. Our data highlight the importance of Vif in HIV-1 pathogenesis and also provide a unique tool to investigate the interaction of Vif and Apobec3G.
Program in Molecular Medicine and Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Melissa A
MA
Farrow
Mohan
M
Somasundaran
Chengsheng
C
Zhang
Dana
D
Gabuzda
John L
JL
Sullivan
Thomas C
TC
Greenough
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D016346:Gene Products, vif / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D017422:Sequence Analysis, DNA; D054320:vif Gene Products, Human Immunodeficiency Virus
D016346:Gene Products, vif; D054320:vif Gene Products, Human Immunodeficiency Virus