Sequence variability of the HIV type 1 protease gene in thai patients experienced with antiretroviral therapy.
One hundred sequences of HIV-1 protease with the two flanking cleavage sites from 10 antiretroviral drug-treated Thai patients were examined for residue variability and for mutations at positions associated with the resistance to protease inhibitors. Seven patients were infected with CRF01_AE, two with subtype B, and one with a strain that did not belong to any of the currently identified subtypes or recombinant forms. A total of 46 out of the 99 positions (46%) in HIV-1 protease showed at least one amino acid change as compared with the HXB2 subtype B protease. Interestingly, 35% of these mutations were at positions associated with resistance to the PIs. The observation indicated that the viral protease is flexible in tolerating some degree of amino acid substitutions even in the critical regions under the selective pressure driven by antiretroviral drugs. The PR/RT cleavage site revealed conservation of the HXB2 sequence. Nevertheless, the p6*/PR cleavage site displayed variability, notably in the p6* region.
Nukoolkarn
Sarawut
S
Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, 10400, Thailand.
Pongthapisith
Viroj
V
Panyim
Sakol
S
Leelamanit
Wichet
W
D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics; D014644:Genetic Variation; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology*; D016333:HIV Protease / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000145:classification / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D013785:Thailand / Q000453:epidemiology
D044966:Anti-Retroviral Agents; D017320:HIV Protease Inhibitors; D016333:HIV Protease