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

Clinical Research Center, National Hospital Organization Nagoya Medical Center, Tokai Area Central Hospital for AIDS Treatment and Research, Nagoya, Aichi 460-0001, Japan.
AIDS research and human retroviruses (Impact Factor: 2.33). 08/2008; 24(8):1121-5. DOI: 10.1089/aid.2008.0090
Source: PubMed


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.

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    • "Amino acid residue 87H is located in the L4/5 and H87Q mutation reduces incorporation of cyclophilin A (CypA) into HIV-1 virions (Gatanaga et al., 2006). H87Q was also observed in protease inhibitor-resistant viruses (Gatanaga et al., 2002) as well as non-nucleoside reverse transcriptase inhibitor-resistant viruses (Ibe et al., 2008). It remains to be elucidated whether mutations in CTL escape or drug-resistant viruses and compensatory mutations in revertant viruses affect viral sensitivity to human TRIM5α. "
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