Nuclear localization of HIV type 1 Vif isolated from a long-term asymptomatic individual and potential role in virus attenuation
Authors
Farrow, Melissa AnnSomasundaran, Mohan
Zhang, Chengsheng
Gabuzda, Dana
Sullivan, John L.
Greenough, Thomas C.
Document Type
Journal ArticlePublication Date
2005-06-01Keywords
Amino Acid MotifsAmino Acid Sequence
Cell Line
Cell Nucleus
Gene Products, vif
HIV Long-Term Survivors
HIV-1
Humans
Molecular Sequence Data
Mutation
Sequence Analysis, DNA
vif Gene Products, Human Immunodeficiency Virus
Immunology and Infectious Disease
Pediatrics
Metadata
Show full item recordAbstract
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.Source
AIDS Res Hum Retroviruses. 2005 Jun;21(6):565-74. Link to article on publisher's siteDOI
10.1089/aid.2005.21.565Permanent Link to this Item
http://hdl.handle.net/20.500.14038/43462PubMed ID
15989462Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1089/aid.2005.21.565