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检测巴西东北部不同的人类免疫缺陷病毒 1 型循环重组形式。

Detection of distinct human immunodeficiency virus type 1 circulating recombinant forms in northeast Brazil.

机构信息

Advanced Public Health Laboratory, Gonçalo Moniz Research Center, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil.

出版信息

J Med Virol. 2011 Dec;83(12):2066-72. doi: 10.1002/jmv.22170.

Abstract

The extraordinary genetic diversity and immune evasion of human immunodeficiency virus (HIV) pose significant challenges for vaccine development and antiretroviral therapy efficacy. The objective of this study was to characterize the molecular profile of HIV-1 epidemic in Salvador, Bahia, Brazil, determining the genetic subtypes and the presence of antiretroviral resistance mutations. HIV-1 pol DNA sequences from 57 individuals infected with HIV were obtained by PCR, followed by sequencing. The subtypes were determined by phylogenetic analyses and the intersubtype recombination was investigated by bootscanning. The pol subtypes were compared with gag and env subtypes. Antiretroviral susceptibility was evaluated through the Stanford HIV resistance Database. The subtypes frequencies were: 77.2% of subtype B, 1.8% of subtype F1, and 21.0% of BF recombinant forms. Two intergenic and three intragenic BF recombinant patterns were observed. Six (10.5%) viruses were related to CRF28/CRF29, two were related to CRF12 (3.5%), and one (1.8%) was CRF39. Fourteen (24.6%) strains carried one or more mutations associated with at least intermediate resistance: 24.6% had resistance to nucleoside reverse transcriptase inhibitors, 21.0% to non-nucleoside reverse transcriptase inhibitors, and 7% to protease inhibitors. The substitutions I54V (7.0%), M184V (14.0%), and K103N (10.5%) were the most frequent within each class of drugs. The results show a high diversity of BF genotypes and a lower prevalence of major reverse transcriptase and protease drug resistance mutations in Salvador, compared with other regions of Brazil. These findings may contribute to improve treatment strategies of patients infected with HIV-1 from this Brazilian region.

摘要

人类免疫缺陷病毒(HIV)的遗传多样性和免疫逃逸能力非常强,这给疫苗开发和抗逆转录病毒治疗的效果带来了巨大的挑战。本研究的目的是分析巴西萨尔瓦多 HIV-1 流行的分子特征,确定基因亚型和抗逆转录病毒耐药突变的存在。通过 PCR 扩增和测序获得了 57 名 HIV 感染者的 HIV-1 pol DNA 序列。通过系统发育分析确定基因亚型,通过 bootscanning 分析确定基因重组。将 pol 亚型与 gag 和 env 亚型进行比较。通过斯坦福 HIV 耐药数据库评估抗逆转录病毒的敏感性。各亚型的流行率分别为:B 亚型占 77.2%,F1 亚型占 1.8%,BF 重组形式占 21.0%。观察到两种间插区和三种内插区 BF 重组模式。6 种(10.5%)病毒与 CRF28/CRF29 有关,2 种与 CRF12 有关(3.5%),1 种(1.8%)与 CRF39 有关。14 株(24.6%)病毒携带一种或多种与至少中度耐药相关的突变:核苷类逆转录酶抑制剂耐药占 24.6%,非核苷类逆转录酶抑制剂耐药占 21.0%,蛋白酶抑制剂耐药占 7%。每个药物类别中最常见的突变包括 I54V(7.0%)、M184V(14.0%)和 K103N(10.5%)。与巴西其他地区相比,萨尔瓦多的 BF 基因型具有高度多样性,主要逆转录酶和蛋白酶耐药突变的流行率较低。这些发现可能有助于改善来自该巴西地区 HIV-1 感染者的治疗策略。

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