Human immunodeficiency virus type 1 subtype F reverse transcriptase sequence and drug susceptibility

Human immunodeficiency virus type 1 subtype F reverse transcriptase sequence and drug susceptibility
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DOI:
10.1128/jvi.72.5.3534-3538.1998
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发表时间:
1998-05-01
影响因子:
5.4
通讯作者:
Brun-Vézinet, F
Brun-Vézinet, F
中科院分区:
医学2区
文献类型:
--
作者:
Apetrei, C;Descamps, D;Brun-Vézinet, F

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我们对14株来自罗马尼亚患者的人类免疫缺陷病毒1型(HIV-1)分离株的pol基因的逆转录酶(RT)区域进行了测序和遗传学分析,这些分离株根据env基因结构被归类为F亚型。RT序列显示,这些毒株在遗传学上聚类,并且与其他HIV-1亚型等距,如相邻连接和最大似然方法所示,使我们能够根据pol分类来定义HIV-1亚型F。F亚型RT序列与已报道的M组RT序列的核苷酸和氨基酸差异分别为10.94%和7.6%。F亚型对三类抗逆转录病毒化合物敏感性的表型分析表明,对于一种天然耐药的菌株,四氢咪唑并[4,5,1-jk] [1,4] -苯并二氮杂卓-2-(1H)-酮和-N-(1H)-苯并二氮杂卓(TIBO)衍生物R82913的50%抑制浓度增加。这第一次报告亚型F pol序列证实了完美的env和pol分析确定的系统发育位置之间的相关性,并表明病毒的变异性可能会影响抗逆转录病毒治疗的疗效。这一发现保证了对HIV-1亚型对抗逆转录病毒药物的表型和基因型易感性进行全球评估。
We sequenced and phylogenetically analyzed the reverse transcriptase (RT) regions of the pol genes of 14 human immunodeficiency virus type 1 (HIV-1) isolates from Romanian patients, which were classified as subtype F on the basis of env gene structure. The RT sequences showed that the strains clustered phylogenetically and were equidistant from other HIV-1 subtypes as shown by the neighbor-joining and maximum-likelihood methods, allowing us to define HIV-1 subtype F according to the pol classification. The subtype F RT sequences differed from reported group M RT sequences by 10.94% (for nucleotides) and 7.6% (for amino acids). Phenotypic analysis of subtype F susceptibility to three classes of antiretroviral compounds showed an increase in the 50% inhibitory concentration of the tetrahydroimidazo [4,5,1-jk] [1,4] -benzodiazepin-2-(1H)-one and -thione (TIBO) derivate R82913 for one strain which was naturally resistant to this compound. This first report of subtype F pol sequences confirms the perfect correlation between the phylogenetic positions determined by env and pol analyses and suggests that virus variability might influence the efficacy of antiretroviral treatments. This finding warrants a global evaluation of the phenotypic and genotypic susceptibility of HIV-1 subtypes to antiretroviral drugs.