Compensatory role of human immunodeficiency virus central polypurine tract sequence in kinetically disrupted reverse transcription.
We tested whether the additional positive-strand DNA synthesis initiation of human immunodeficiency virus type 1 (HIV-1) from the central polypurine tract (cPPT) facilitates efficient completion of kinetically disturbed proviral DNA synthesis induced by dysfunctional reverse transcriptase (RT) mutants or limited cellular deoxynucleoside triphosphate (dNTP) pools. Indeed, the cPPT enabled the HIV-1 vectors harboring RT mutants with reduced dNTP binding affinity to transduce human lung fibroblasts (HLFs), without which these mutant vectors normally fail to transduce. The cPPT showed little effect on wild-type HIV-1 vector transduction in HLF, whereas it significantly enhanced vector transduction in HLFs engineered to contain reduced dNTP pools, suggesting a novel compensatory role for cPPT in viruses harboring kinetically impaired RT.
Skasko
Mark
M
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Kim
Baek
B
D002478:Cells, Cultured; D004279:DNA, Viral / Q000096:biosynthesis*; D005347:Fibroblasts; D054303:HIV Reverse Transcriptase / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D048348:Reverse Transcription; D014161:Transduction, Genetic
D004279:DNA, Viral; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase