Human APOBEC3G-mediated editing can promote HIV-1 sequence diversification and accelerate adaptation to selective pressure.
Human apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G, hereinafter referred to as A3G) is an innate virus restriction factor that inhibits human immunodeficiency virus type 1 (HIV-1) replication and induces excessive deamination of cytidine residues in nascent reverse transcripts. To test the hypothesis that this enzyme can also help generate viral sequence diversification and the evolution of beneficial viral variants, we have examined the impact of A3G on the acquisition of (-)2',3'-dideoxy-3'-thiacytidine (3TC) resistance in vitro. That characteristic resistance mutations are rapidly fixed in the presence of A3G and 3TC suggests that A3G-mediated editing can be an important source of genetic variation on which natural selection acts to shape the structure of HIV-1 populations.
Kim
Eun-Young
EY
Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Bhattacharya
Tanmoy
T
Kunstman
Kevin
K
Swantek
Peter
P
Koning
Fransje A
FA
Malim
Michael H
MH
Wolinsky
Steven M
SM
D000071480:APOBEC-3G Deaminase; D019380:Anti-HIV Agents / Q000494:pharmacology; D001483:Base Sequence; D002460:Cell Line; D003564:Cytidine Deaminase / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics; D005814:Genes, Viral; D014644:Genetic Variation; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D019259:Lamivudine / Q000494:pharmacology; D009154:Mutation; D017393:RNA Editing / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D012641:Selection, Genetic
D019380:Anti-HIV Agents; D017931:DNA Primers; D012333:RNA, Messenger; D012367:RNA, Viral; D019259:Lamivudine; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase