Extensive polymorphisms observed in HIV-1 clade B protease gene using high-density oligonucleotide arrays.
Naturally occurring mutations in HIV-1-infected patients have important implications for therapy and the outcome of clinical studies. However, little is known about the prevalence of mutations that confer resistance to HIV-1 protease inhibitors in isolates derived from patients naive for such inhibitors. In the first clinical application of high-density oligonucleotide array sequencing, the sequences of 167 viral isolates from 102 patients have been determined. The DNA sequence of USA HIV-1 clade B proteases was found to be extremely variable and 47.5% of the 99 amino acid positions varied. This level of amino acid diversity is greater than that previously known for all worldwide HIV-1 clades combined (40%). Many of the amino acid changes that are known to contribute to drug resistance occurred as natural polymorphisms in isolates from patients who had never received protease inhibitors.
Kozal
M J
MJ
Department of Molecular Biology, Affymetrix, Santa Clara, California 95051, USA.
Shah
N
N
Shen
N
N
Yang
R
R
Fucini
R
R
Merigan
T C
TC
Richman
D D
DD
Morris
D
D
Hubbell
E
E
Chee
M
M
Gingeras
T R
TR
D000595:Amino Acid Sequence; D001483:Base Sequence; D004352:Drug Resistance, Microbial / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy; D016333:HIV Protease / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000201:enzymology*; D006801:Humans; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000235:genetics*; D011110:Polymorphism, Genetic
D017320:HIV Protease Inhibitors; D009841:Oligonucleotides; D016333:HIV Protease