Sequence variability of the integrase protein from a diverse collection of HIV type 1 isolates representing several subtypes.
HIV-1 recombinants between viruses from different subtypes appear to be surprisingly common in several regions of the world. To detect such intersubtype recombinants that contain mosaic genomes, we have analyzed sequences from the integrase (IN)-coding region of the polymerase (pol) gene from 23 viruses of known envelope (env) subtype from South America and Africa. As defined by env sequences, these viral genomes included nine subtype A, four subtype B, three subtype C, and four subtype D viruses from group M, and three viruses from group O HIV-1. Mosaic genomes were common, with 7 mosaic genomes among the 20 group M isolates analyzed. Two of these isolates had mosaic IN-coding regions that were distinct, but that had recombination breakpoints at the same location, in the highly conserved polypurine track. Mosaic genomes were particularly common in the viruses from Kenya (five of nine), consistent with our previous prediction that there was a high frequency of intersubtype recombinants circulating in this country. The IN amino acid sequence was highly conserved among the several represented subtypes, including group O. Group M IN sequences shared 94% or greater amino acid sequence identity within a subtype and 91% or greater identity between subtypes. The most divergent M and O variant amino acid sequences differed by only 19%, and the known functional domains were conserved among all of the isolates. The high degree of genetic homogeneity among the virus isolates representing several subtypes indicates that a single drug targeted against IN might be effective for all HIV-1 infections.
Burns
Cara Carthel
CC
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. cburns@cdc.gov
Gleason
Lisa M
LM
Mozaffarian
Afsaneh
A
Giachetti
Cristina
C
Carr
Jean K
JK
Overbaugh
Julie
J
D000351:Africa, Eastern; D000595:Amino Acid Sequence; D001938:Brazil; D004279:DNA, Viral / Q000032:analysis; D014644:Genetic Variation; D015658:HIV Infections / Q000821:virology; D019427:HIV Integrase / Q000737:chemistry* / Q000235:genetics*; D015497:HIV-1 / Q000145:classification* / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA
D004279:DNA, Viral; D019427:HIV Integrase