Vpr is required for efficient Nef expression from unintegrated human immunodeficiency virus type 1 DNA.
Unintegrated human immunodeficiency virus (HIV) DNA are viral DNA products formed naturally during HIV replication. While the integrated proviral DNA form is transcriptionally active and results in productive infection, unintegrated DNA is also capable of expression of viral RNA and proteins. Previously, we showed that HIV Vpr enhances expression from integrase-defective HIV. Here we show that Vpr activation of expression is partially dependent upon the presence of a transcriptionally active HIV promoter and results in increased transcription of unspliced gag and spliced nef viral RNA. While Tat is detectable during infection with integrase-defective HIV, Tat levels are not affected by the presence of Vpr. Mutation studies reveal that Tat is dispensable for the Vpr-mediated enhancement of expression from unintegrated DNA. We find that virion-associated Vpr is sufficient for Nef expression from unintegrated viral DNA, resulting in the efficient downregulation of CD4 from the surface of infected cells. These results provide a mechanism by which Nef expression from unintegrated HIV type 1 DNA expression occurs.
Poon
Betty
B
Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at UCLA, UCLA AIDS Institute and Jonsson Comprehensive CAncer Center, 11-934 Factor Building, 10833 Le Conte Avenue, Los Angeles, CA 90095-1678, USA.
Chang
Michael A
MA
Chen
Irvin S Y
IS
D015704:CD4 Antigens / Q000235:genetics; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics; D015536:Down-Regulation; D015967:Gene Expression Regulation, Viral; D015693:Gene Products, nef / Q000235:genetics*; D015696:Gene Products, tat / Q000235:genetics; D016336:Gene Products, vpr / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D009154:Mutation; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D016662:Virus Integration; D014779:Virus Replication / Q000235:genetics*; D054311:nef Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus
D015704:CD4 Antigens; D004279:DNA, Viral; D015693:Gene Products, nef; D015696:Gene Products, tat; D016336:Gene Products, vpr; D054311:nef Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus