Suwellen Sardinha Dias de Azevedo, Fernanda Heloise Côrtes, Mariza G Morgado, Brenda Hoagland, Larissa M Villela, Beatriz Grinsztejn, Valdilea Gonçalvez Veloso, Gonzalo Bello
{"title":"HIV-1精英控制者中与Vif和Vpr衰减相关的多态性鉴定","authors":"Suwellen Sardinha Dias de Azevedo, Fernanda Heloise Côrtes, Mariza G Morgado, Brenda Hoagland, Larissa M Villela, Beatriz Grinsztejn, Valdilea Gonçalvez Veloso, Gonzalo Bello","doi":"10.1590/0074-02760240274","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Findings: </strong>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.</p><p><strong>Main conclusions: </strong>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.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":"120 ","pages":"e240274"},"PeriodicalIF":2.5000,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208676/pdf/","citationCount":"0","resultStr":"{\"title\":\"Identification of polymorphisms associated with attenuation of Vif and Vpr in HIV-1 Elite Controllers.\",\"authors\":\"Suwellen Sardinha Dias de Azevedo, Fernanda Heloise Côrtes, Mariza G Morgado, Brenda Hoagland, Larissa M Villela, Beatriz Grinsztejn, Valdilea Gonçalvez Veloso, Gonzalo Bello\",\"doi\":\"10.1590/0074-02760240274\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Findings: </strong>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.</p><p><strong>Main conclusions: </strong>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.</p>\",\"PeriodicalId\":18469,\"journal\":{\"name\":\"Memorias do Instituto Oswaldo Cruz\",\"volume\":\"120 \",\"pages\":\"e240274\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2025-06-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208676/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Memorias do Instituto Oswaldo Cruz\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1590/0074-02760240274\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"PARASITOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Memorias do Instituto Oswaldo Cruz","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1590/0074-02760240274","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"PARASITOLOGY","Score":null,"Total":0}
Identification of polymorphisms associated with attenuation of Vif and Vpr in HIV-1 Elite Controllers.
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.
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
