Kinetics of human immunodeficiency virus type 1 reverse transcription in blood mononuclear phagocytes are slowed by limitations of nucleotide precursors.
Human immunodeficiency virus type 1 infection of mononuclear phagocytes has been implicated in disease manifestations, but postentry viral replication events in these cells have not been well characterized. Productive infection of activated T cells is associated with cell proliferation and accumulation of full-length viral DNA within 6 h. In infected, nondividing quiescent peripheral blood lymphocytes, reverse transcription is aborted prior to full-length viral DNA formation. For nondividing, cultured mononuclear phagocytes, we now report a third pattern of reverse transcription with relatively slow kinetics, in which full-length viral DNA did not accumulate until 36 to 48 h. The reverse transcription rate in mononuclear phagocytes could be accelerated by addition of exogenous nucleotide precursors, but still not to the rate seen in activated T cells. These results indicate that substrate limitations in mononuclear phagocytes slow but do not arrest human immunodeficiency virus type 1 reverse transcription.
O'Brien
W A
WA
Department of Medicine, Veterans Affairs Medical Center, West Los Angeles, California 90073.
Namazi
A
A
Kalhor
H
H
Mao
S H
SH
Zack
J A
JA
Chen
I S
IS
D015526:AIDS Dementia Complex / Q000382:microbiology; D002478:Cells, Cultured; D004279:DNA, Viral / Q000096:biosynthesis; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D006801:Humans; D008264:Macrophages / Q000382:microbiology*; D009000:Monocytes / Q000382:microbiology*; D009711:Nucleotides / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism*; D014158:Transcription, Genetic; D014779:Virus Replication; D015215:Zidovudine / Q000494:pharmacology
D004279:DNA, Viral; D009711:Nucleotides; D015215:Zidovudine; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase