逆转录病毒对整合酶链转移抑制剂的敏感性差异。
Differential sensitivities of retroviruses to integrase strand transfer inhibitors.
机构信息
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney Street, CLS-1010, Boston, MA 02115, USA.
出版信息
J Virol. 2011 Apr;85(7):3677-82. doi: 10.1128/JVI.02541-10. Epub 2011 Jan 26.
Abstract
Integrase inhibitors are emerging anti-human immunodeficiency virus (HIV) drugs, and multiple retroviruses and transposable elements were evaluated here for susceptibilities to raltegravir (RAL) and elvitegravir (EVG). All viruses, including primate and nonprimate lentiviruses, a Betaretrovirus, a Gammaretrovirus, and the Alpharetrovirus Rous sarcoma virus (RSV), were susceptible to inhibition by RAL. EVG potently inhibited all lentiviruses and intermediately inhibited Betaretrovirus and Gammaretrovirus infections yet was basically ineffective against RSV. Substitutions based on HIV type 1 (HIV-1) resistance changes revealed that integrase residue Ser150 contributed significantly to the resistance of RSV. The drugs intermediately inhibited intracisternal A-particle retrotransposition but were inactive against Sleeping Beauty transposition and long interspersed nucleotide element 1 (LINE-1) retrotransposition.
摘要
整合酶抑制剂是新兴的抗人类免疫缺陷病毒（HIV）药物，本研究评估了多种逆转录病毒和转座元件对拉替拉韦（RAL）和艾维雷格（EVG）的敏感性。所有病毒，包括灵长类和非灵长类慢病毒、β逆转录病毒、γ逆转录病毒和α逆转录病毒劳斯肉瘤病毒（RSV），均对 RAL 的抑制作用敏感。EVG 强烈抑制所有慢病毒，并适度抑制β逆转录病毒和γ逆转录病毒感染，但对 RSV 基本无效。基于 HIV-1（HIV-1）耐药性变化的替代表明，整合酶残基 Ser150 对 RSV 的耐药性有重要贡献。这些药物对核内 A 颗粒逆转录转座有中度抑制作用，但对睡美人转座和长散布核苷酸元件 1（LINE-1）逆转录转座无活性。
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