Antiretroviral Drug Resistance in HIV-2: Three Amino Acid Changes Are Sufficient for Classwide Nucleoside Analogue Resistance
Antiretroviral Drug Resistance in HIV-2: Three Amino Acid Changes Are Sufficient for Classwide Nucleoside Analogue Resistance
复制标题
DOI：
10.1086/597802
复制
发表时间：
2009-05-01
影响因子：
6.4
通讯作者：
Gottlieb, Geoffrey S.
中科院分区：
文献类型：
--
作者：
Smith, Robert A.;Anderson, Donovan J.;Gottlieb, Geoffrey S.
基因型调查表明，人类免疫缺陷病毒1型（HIV-1）和HIV-2进化不同的突变集响应核苷逆转录酶抑制剂（NRTI）。我们使用定点诱变，培养为基础的表型分析，和无细胞测定，以确定特定的氨基酸取代在HIV-2逆转录酶赋予的耐药谱。虽然胸苷类似物突变对齐多夫定敏感性没有影响，但Q151 M与K65 R或M184 V的联合足以使HIV-2对拉米夫定和齐多夫定产生高水平的耐药性，K65 R、Q151 M和M184 V的联合赋予了全类NRTI耐药性。这些数据表明，目前基于NRTI的治疗方案对于治疗HIV-2感染是次优的。
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.