APOBEC3G inhibits elongation of HIV-1 reverse transcripts.
APOBEC3G (A3G) is a host cytidine deaminase that, in the absence of Vif, restricts HIV-1 replication and reduces the amount of viral DNA that accumulates in cells. Initial studies determined that A3G induces extensive mutation of nascent HIV-1 cDNA during reverse transcription. It has been proposed that this triggers the degradation of the viral DNA, but there is now mounting evidence that this mechanism may not be correct. Here, we use a natural endogenous reverse transcriptase assay to show that, in cell-free virus particles, A3G is able to inhibit HIV-1 cDNA accumulation not only in the absence of hypermutation but also without the apparent need for any target cell factors. We find that although reverse transcription initiates in the presence of A3G, elongation of the cDNA product is impeded. These data support the model that A3G reduces HIV-1 cDNA levels by inhibiting synthesis rather than by inducing degradation.
Bishop
Kate N
KN
Department of Infectious Diseases, King's College London School of Medicine, Guy's Hospital, London, United Kingdom.
Verma
Mohit
M
Kim
Eun-Young
EY
Wolinsky
Steven M
SM
Malim
Michael H
MH
D000071480:APOBEC-3G Deaminase; D002460:Cell Line; D003564:Cytidine Deaminase / Q000235:genetics / Q000502:physiology*; D018076:DNA, Complementary / Q000096:biosynthesis; D004279:DNA, Viral / Q000096:biosynthesis*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D048348:Reverse Transcription; D014779:Virus Replication; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000235:genetics
D018076:DNA, Complementary; D004279:DNA, Viral; D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase