Smith Robert A, Anderson Donovan J, Pyrak Crystal L, Preston Bradley D, Gottlieb Geoffrey S
Department of Pathology, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA 98133, USA.
J Infect Dis. 2009 May 1;199(9):1323-6. doi: 10.1086/597802.
Genotypic surveys suggest that human immunodeficiency virus type 1 (HIV-1) and HIV-2 evolve different sets of mutations in response to nucleoside reverse-transcriptase inhibitors (NRTIs). We used site-directed mutagenesis, culture-based phenotyping, and cell-free assays to determine the resistance profiles conferred by specific amino acid replacements in HIV-2 reverse transcriptase. Although thymidine analogue mutations had no effect on zidovudine sensitivity, the addition of Q151M together with K65R or M184V was sufficient for high-level resistance to both lamivudine and zidovudine in HIV-2, and the combination of K65R, Q151M, and M184V conferred classwide NRTI resistance. These data suggest that current NRTI-based regimens are suboptimal for treating HIV-2 infection.
基因分型调查表明，1型人类免疫缺陷病毒（HIV-1）和HIV-2在对核苷类逆转录酶抑制剂（NRTIs）产生反应时会发生不同的突变。我们使用定点诱变、基于培养的表型分析和无细胞检测来确定HIV-2逆转录酶中特定氨基酸替换所赋予的耐药谱。尽管胸苷类似物突变对齐多夫定敏感性没有影响，但在HIV-2中，Q151M与K65R或M184V同时出现足以导致对拉米夫定和齐多夫定的高水平耐药，而K65R、Q151M和M184V的组合则导致对所有NRTIs耐药。这些数据表明，目前基于NRTIs的治疗方案在治疗HIV-2感染方面并非最佳选择。
