Identification of polymorphisms associated with attenuation of Vif and Vpr in HIV-1 Elite Controllers.

IF 2.5 4区医学 Q2 PARASITOLOGY

Memorias do Instituto Oswaldo Cruz Pub Date : 2025-06-27 eCollection Date: 2025-01-01 DOI:10.1590/0074-02760240274

Suwellen Sardinha Dias de Azevedo, Fernanda Heloise Côrtes, Mariza G Morgado, Brenda Hoagland, Larissa M Villela, Beatriz Grinsztejn, Valdilea Gonçalvez Veloso, Gonzalo Bello

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引用次数: 0

Abstract

Background: Elite controllers (ECs) are a rare subset of individuals who naturally suppress human immunodeficiency virus type 1 (HIV-1) replication in the absence of antiretroviral therapy. Specific polymorphisms in the accessory proteins Vif and Vpr have been associated with diminished viral fitness in vitro and are more frequently detected in ECs compared to other individuals infected with HIV-1.

Objective: To assess the frequency of gross genetic defects or polymorphisms that may attenuate the function of the HIV-1 accessory proteins Vif and Vpr within the proviral quasispecies of ECs.

Methods: We performed single-genome amplification (SGA) and sequence analysis of the proviral quasispecies of the accessory genes vif and vpr in samples obtained from eight ECs with over 10 years of suppressive viral control and no evidence of disease progression.

Findings: In subjects EC11, EC38 and EC52, most proviral clones encode full-length, intact vif and vpr open reading frames without known attenuating polymorphisms. Subject EC35 displayed stop codons in a substantial fraction of vif (33%) and vpr (67%) proviral clones. Subject EC36 exhibited the attenuating polymorphisms Vpr-Q3R + R77Q combined in all proviral clones. Subject EC17 showed stop codons in 20-30% of vif-vpr proviral clones, hypermutated sequences in 20% of vif proviral clones, and the attenuating polymorphism Vpr-R77Q in all proviral clones. Subject EC19 presented stop codons in 8-17% of vif-vpr proviral sequences, hypermutated sequences in 25% of vif-vpr proviral clones, and the polymorphisms Vif-R132S+Ins61(EDK) and Vpr-R77Q in all clones analysed. Finally, subject EC42 displayed stop codons in 25-38% of vif-vpr proviral sequences, hypermutated sequences in 25% of vif proviral clones, and the polymorphisms Vif-T20A+R132S and Vpr-R77Q in most (> 80%) proviral clones.

Main conclusions: Mutations associated with attenuation of HIV-1 Vif and/or Vpr functions may contribute to the long-term control of viral replication and disease progression in certain ECs.

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HIV-1精英控制者中与Vif和Vpr衰减相关的多态性鉴定

背景：精英控制者（ec）是在没有抗逆转录病毒治疗的情况下自然抑制人类免疫缺陷病毒1型（HIV-1）复制的罕见个体。辅助蛋白Vif和Vpr的特异性多态性与体外病毒适应性降低有关，与其他感染HIV-1的个体相比，在ECs中更常检测到。目的：评估可能削弱HIV-1辅助蛋白Vif和Vpr在ECs原病毒准种中的功能的严重遗传缺陷或多态性的频率。方法：对8例病毒抑制控制超过10年且无疾病进展的ECs样本进行了前病毒准种vif和vpr辅助基因的单基因组扩增（SGA）和序列分析。结果：在受试者EC11、EC38和EC52中，大多数原病毒克隆编码全长、完整的vif和vpr开放阅读框，没有已知的衰减多态性。受试者EC35在大部分vif（33%）和vpr（67%）原克隆中显示停止密码子。实验对象EC36在所有原病毒克隆中均表现出Vpr-Q3R + R77Q组合的衰减多态性。受试者EC17在20-30%的vif-vpr原病毒克隆中发现停止密码子，在20%的vif原病毒克隆中发现超突变序列，在所有的原病毒克隆中发现衰减多态性Vpr-R77Q。受试者EC19在8-17%的vif-vpr原病毒序列中存在终止密码子，在25%的vif-vpr原病毒克隆中存在超突变序列，在所有克隆中存在Vif-R132S+Ins61（EDK）和Vpr-R77Q多态性。最后，受试者EC42在25-38%的vif-vpr原病毒序列中显示停止密码子，在25%的vif原病毒克隆中显示超突变序列，在大多数（约80%）原病毒克隆中显示vif- t20a +R132S和Vpr-R77Q多态性。主要结论：与HIV-1 Vif和/或Vpr功能衰减相关的突变可能有助于在某些ECs中长期控制病毒复制和疾病进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Memorias do Instituto Oswaldo Cruz 医学-寄生虫学

CiteScore

5.00

自引率

3.60%

发文量

审稿时长

3-8 weeks

期刊介绍： Memórias do Instituto Oswaldo Cruz is a journal specialized in microbes & their vectors causing human infections. This means that we accept manuscripts covering multidisciplinary approaches and findings in the basic aspects of infectious diseases, e.g. basic in research in prokariotes, eukaryotes, and/or virus. Articles must clearly show what is the main question to be answered, the hypothesis raised, and the contribution given by the study. Priority is given to manuscripts reporting novel mechanisms and general findings concerning the biology of human infectious prokariotes, eukariotes or virus. Papers reporting innovative methods for diagnostics or that advance the basic research with these infectious agents are also welcome. It is important to mention what we do not publish: veterinary infectious agents research, taxonomic analysis and re-description of species, epidemiological studies or surveys or case reports and data re-analysis. Manuscripts that fall in these cases or that are considered of low priority by the journal editorial board, will be returned to the author(s) for submission to another journal.