Inhibition of tRNA₃(Lys)-primed reverse transcription by human APOBEC3G during human immunodeficiency virus type 1 replication.
Cells are categorized as being permissive or nonpermissive according to their ability to produce infectious human immunodeficiency virus type 1 (HIV-1) lacking the viral protein Vif. Nonpermissive cells express the human cytidine deaminase APOBEC3G (hA3G), and Vif has been shown to bind to APOBEC3G and facilitate its degradation. Vif-negative HIV-1 virions produced in nonpermissive cells incorporate hA3G and have a severely reduced ability to produce viral DNA in newly infected cells. While it has been proposed that the reduction in DNA production is due to hA3G-facilitated deamination of cytidine, followed by DNA degradation, we provide evidence here that a decrease in the synthesis of the DNA by reverse transcriptase may account for a significant part of this reduction. During the infection of cells with Vif-negative HIV-1 produced from 293T cells transiently expressing hA3G, much of the inhibition of early (> or =50% reduction) and late (> or =95% reduction) viral DNA production, and of viral infectivity (> or =95% reduction), can occur independently of DNA deamination. The inhibition of the production of early minus-sense strong stop DNA is also correlated with a similar inability of tRNA(3)(Lys) to prime reverse transcription. A similar reduction in tRNA(3)(Lys) priming and viral infectivity is also seen in the naturally nonpermissive cell H9, albeit at significantly lower levels of hA3G expression.
Guo
Fei
F
Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Cote St. Catherine Road, Montreal, Quebec, Canada H3T 1E2.
Cen
Shan
S
Niu
Meijuan
M
Saadatmand
Jenan
J
Kleiman
Lawrence
L
D000071480:APOBEC-3G Deaminase; D002460:Cell Line; D003564:Cytidine Deaminase; D005786:Gene Expression Regulation; D016346:Gene Products, vif / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009700:Nucleoside Deaminases / Q000737:chemistry / Q000494:pharmacology*; D012097:Repressor Proteins / Q000737:chemistry / Q000494:pharmacology*; D048348:Reverse Transcription / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects* / Q000502:physiology; D054320:vif Gene Products, Human Immunodeficiency Virus
D016346:Gene Products, vif; D012097:Repressor Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase