Nature Medicine
2, 753 - 759 (1996)
doi:10.1038/nm0796-753
Extensive polymorphisms observed in HIV−1 clade B protease gene using high−density oligonucleotide arraysMichael J. Kozal1, 4, Nila Shah1, Naiping Shen1, Robert Yang1, Raymond Fucini1, Thomas C. Merigan2, Douglas D. Richman3, Don Morris1, Earl Hubbell1, Mark Chee1
& Thomas R. Gingeras1
1Department of Molecular Biology, Affymetrix, 3380 Central Expressway, Santa Clara, California 95051, USA
2Division of Infectious Diseases, Stanford University, Stanford, California 94305, USA
3Departments of Pathology and Medicine, University of California San Diego, La Jolla, California 92093, USA, and San Diego Veterans Affairs Medical Center, San Diego, California 92161, USA
4Division of Infectious Disease, University ofIowa, Iowa City, Iowa 52246, USA
5Correspondence should be addressed to T.R.G. 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 arraysequencing, 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.% 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.
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