Functional integrity of naturally occurring mutants of HIV-1 subtype C Vpr.
HIV-1 Vpr, an accessory protein with multiple functions, is involved in the induction of apoptosis, cell cycle G2 arrest, and modulation of gene expression. Many functions of this protein have been documented for the wild-type subtype B Vpr, however the functionality of other subtypes has not sufficiently been addressed. In this study, the functionality of Subtype B Vpr, 6 subtype C mutant Vpr proteins and the consensus sequence of subtype C Vpr were compared with each other. All the subtype B and C Vpr proteins localized to the nucleus of human 293T cells. Subtype C Vpr proteins induced cell cycle G2 arrest in a lower proportion of human 293T cells compared to subtype B Vpr. Subtype B and the naturally mutant Vpr proteins induced apoptosis in a similar manner, ranging from 95.33% to 98.64%. However, an artificially designed Vpr protein containing the consensus sequences of subtype C Vpr indicated a reduced ability in induction of apoptosis. The study of mRNA profile of the transfected cells indicated that all Vpr proteins modulated the apoptotic genes triggering the intrinsic pathway of apoptosis. Our results indicate that subtype C Vpr is able to exert the same functions previously reported for subtype B Vpr. Most natural mutations in Vpr not only do not disturb the functions of the protein but also potentiate the protein for an increased functionality. The natural mutations of Vpr may thus not always be regarded as defective mutations. The study suggests the adaptive role of the natural mutations commonly found in subtype C Vpr.
Romani
Bizhan
B
Division of Medical Virology, Department of Pathology, University of Stellenbosch, Tygerberg 7505, South Africa. bizhan@sun.ac.za
Glashoff
Richard H
RH
Engelbrecht
Susan
S
D017209:Apoptosis; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D020869:Gene Expression Profiling; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D050505:Mutant Proteins / Q000235:genetics* / Q000378:metabolism*; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000378:metabolism*
D050505:Mutant Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1