Extensive polymorphisms observed in HIV|[ndash]|1 clade B protease gene using high|[ndash]|density oligonucleotide arrays

来自 Nature

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122

作者：

MJ Kozal，N Shah，N Shen，R Yang，R Fucini，TC Merigan，DD Richman，D Morris，E Hubbell，M Chee

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摘要：

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.

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关键词：

Humans HIV Infections HIV Protease Oligonucleotides HIV Protease Inhibitors Drug Resistance, Microbial Base Sequence Polymorphism, Genetic Amino Acid Sequence Molecular Sequence Data