| Author | Caetano, Diogo Gama | |
| Author | Côrtes, Fernanda Heloise | |
| Author | Bello, Gonzalo | |
| Author | Teixeira, Sylvia Lopes Maia | |
| Author | Hoagland, Brenda Regina de Siqueira | |
| Author | Grinsztejn, Beatriz | |
| Author | Veloso,Valdiléa G. | |
| Author | Guimarães, Monick Lindenmeyer | |
| Author | Morgado, Mariza Gonçalves | |
| Access date | 2018-12-05T16:21:55Z | |
| Available date | 2018-12-05T16:21:55Z | |
| Document date | 2018 | |
| Citation | CAETANO, Diogo Gama et al. Next-generation sequencing analyses of the emergence and maintenance of mutations in CTL epitopes in HIV controllers with differential viremia control. Retrovirology, v. 15, n. 1, p. 1-13, 2018. | pt_BR |
| ISSN | 1742-4690 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/30402 | |
| Description | Acknowledgements: We thank the patients, nurses, and clinicians who participated in the study. We also thank Egydio Sampaio for support in the recruitment of patients and all INI staff from the blood collection sector. Finally, we are thankful for the CD4+ T cell count and HIV-1 viral load clinical services from the Brazilian Ministry of Health National Network, and the FIOCRUZ PDTIS NGS Platform (RPT01J). | pt_BR |
| Language | eng | pt_BR |
| Publisher | BMC | pt_BR |
| Rights | open access | |
| Title | Next-generation sequencing analyses of the emergence and maintenance of mutations in CTL epitopes in HIV controllers with differential viremia control | pt_BR |
| Type | Article | |
| DOI | 10.1186/s12977-018-0444-z | |
| Abstract | Background: Despite the low level of viral replication in HIV controllers (HICs), studies have reported viral mutations related to escape from cytotoxic T-lymphocyte (CTL) response in HIV-1 plasma sequences. Thus, evaluating the dynamics of the emergence of CTL-escape mutants in HICs reservoirs is important for understanding viremia control. To analyze the HIV-1 mutational profle and dynamics of CTL-escape mutants in HICs, we selected 11 long-term nonprogressor individuals and divided them into the following groups: (1) viremic controllers (VCs; n=5) and (2) elite controllers (ECs; n=6). For each individual, we used HIV-1 proviral DNA from PBMCs related to earliest (VE) and latest (VL) visits to obtain gag and nef sequences using the Illumina HiSeq system. The consensus of each mapped gene was used to assess viral divergence, and next-generation sequencing data were employed to identify SNPs and variations within and fanking CTL epitopes. Results: Divergence analysis showed higher values for nef compared to gag among the HICs. EC and VC groups showed similar divergence rates for both genes. Analysis of the number of SNPs showed that VCs present more variability in both genes. Synonymous/non-synonymous mutation ratios were<1 for gag among ECs and for nef among ECs and VCs, exhibiting a predominance of non-synonymous mutations. Such mutations were observed in regions encoding CTL-restricted epitopes in all individuals. All ECs presented non-synonymous mutations in CTL epitopes but generally at low frequency (<1%); all VCs showed a high number of mutations, with signifcant frequency changes between VE and VL visits. A higher frequency of internal mutations was observed for gag epitopes, with signifcant changes across visits compared to Nef epitopes, indicating a pattern associated with diferential genetic pressure. Conclusions: The high genetic conservation of HIV-1 gag and nef among ECs indicates that the higher level of viremia control restricts the evolution of both genes. Although viral replication levels in HICs are low or undetectable, all individuals exhibited CTL epitope mutations in proviral gag and nef variants, indicating that potential CTL escape mutants are present in HIC reservoirs and that situations leading to a disequilibrium of the host-virus relationship can result in the spread of CTL-escape variants. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Aids e Imunologia Molecular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Aids e Imunologia Molecular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Aids e Imunologia Molecular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Aids e Imunologia Molecular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Aids e Imunologia Molecular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Aids e Imunologia Molecular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | CTL epitope | pt_BR |
| Subject | Escape Mutant | pt_BR |
| Subject | HIV Controller | pt_BR |
| Subject | HIV-1 | pt_BR |
| Subject | Next-Generation Sequencing | pt_BR |
| Subject | Single-nucleotide Polymorphism | pt_BR |
