G-->A hypermutation in protease and reverse transcriptase regions of human immunodeficiency virus type 1 residing in resting CD4+ T cells in vivo.
In vitro studies have shown that the host cytidine deaminase APOBEC3G causes lethal hypermutation in human immunodeficiency virus type 1 reverse transcripts unless its incorporation into virions is blocked by Vif. By examining stably archived sequences in resting CD4+ T cells, we show that hypermutation occurs in most if not all infected individuals. Hypermutated sequences comprised >9% of archived species in resting CD4+ T cells but were not found in plasma virus. Mutations occurred in predicted contexts, with notable hotspots. Thus, defects in Vif function in vivo give rise to hypermutated viral genomes that can be integrated but do not produce progeny viruses.
Kieffer
Tara L
TL
Department of Medicine, Johns Hopkins University School of Medicine, 879 Broadway Research Bldg., 733 N. Broadway, Baltimore, MD 21205, USA.
Kwon
Patty
P
Nettles
Richard E
RE
Han
Yefei
Y
Ray
Stuart C
SC
Siliciano
Robert F
RF
D023241:Antiretroviral Therapy, Highly Active; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000821:virology*; D004197:Disease Reservoirs; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D016333:HIV Protease / Q000235:genetics*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D017735:Virus Latency
D054303:HIV Reverse Transcriptase; D016333:HIV Protease