Potential drug resistance polymorphisms in the integrase gene of HIV type 1 subtype A.
Variation in HIV-1 genes within and between subtypes has been best defined in the env gene, however, other more conserved genes vary between subtypes. Integrase (IN) and other regions of the pol gene are highly conserved due to their integral role in HIV replication and therefore are targets for antiviral drugs. In this study 3 individuals, infected heterosexually with HIV-1 subtype A, were examined for IN polymorphisms. Two patients' sequences clustered phylogenetically with other subtype A sequences and one patient's sequence was most similar to the circulating recombinant form CRF_02. No polymorphisms were observed in either of the motifs containing residues critical residues for IN activity. Polymorphisms were observed in a residue associated with resistance to anti-integrase drugs. In addition, a number of unique polymorphisms were observed in one individual (WM1666). IN can vary significantly within a subtype as well as between subtypes, and mutations associated with resistance to anti-integrase compounds can be present in drug naive individuals.
Herring
Belinda L
BL
Center for Virus Research, Westmead Millennium Institute, Westmead Hospital, Westmead, NSW 2145, Australia. bher1872@itsa.ucsf.edu
Cunningham
Anthony L
AL
Dwyer
Dominic E
DE
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000821:virology; D019427:HIV Integrase / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1 / Q000145:classification / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D020010:Heterosexuality; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA
D019380:Anti-HIV Agents; D019427:HIV Integrase