Analysis of near full-length genomic sequences of drug-resistant HIV-1 spreading among therapy-naïve individuals in Nagoya, Japan: amino acid mutations associated with viral replication activity.
We analyzed a total of 12 near full-length genomes of drug-resistant HIV-1 spreading among therapy-naïve individuals in Nagoya, Japan. Genomes comprised seven protease inhibitor (PI)-resistant viruses possessing an M46I (n = 6) or L90M mutation (n = 1) and five non-nucleoside reverse transcriptase inhibitor-resistant viruses possessing a K103N mutation. All 12 viruses conserved both an H87Q mutation in the cyclophilin A-binding site of Gag p24 (capsid) and a T23N mutation in the cysteine-rich domain of Tat protein. PI-resistant viruses commonly possessed two cleavage site mutations in the p6(Pol)/protease of Pol polyprotein (F48L in p6(Pol)) and the anchor/core domains of Nef protein (L57V). These amino acid mutations represent candidates for enhancing replication activity of drug-resistant viruses and supporting expansion of such viruses in therapy-naïve individuals.
Ibe
Shiro
S
Clinical Research Center, National Hospital Organization Nagoya Medical Center, Tokai Area Central Hospital for AIDS Treatment and Research, Nagoya, Aichi 460-0001, Japan.
Shigemi
Urara
U
Sawaki
Kaori
K
Fujisaki
Seiichiro
S
Hattori
Junko
J
Yokomaku
Yoshiyuki
Y
Mamiya
Naoto
N
Hamaguchi
Motohiro
M
Kaneda
Tsuguhiro
T
D000596:Amino Acids / Q000235:genetics*; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D005814:Genes, Viral / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007564:Japan; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics
D000596:Amino Acids