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Caracterização de variantes virais de HIV-1 em indivíduos soropositivos com perfil de controle da progressão para a AIDS e da replicação viralavaliação da ocorrência de variantes de escape da resposta imune
| Content Provider | Semantic Scholar |
|---|---|
| Author | Caetano, Diogo G. |
| Copyright Year | 2016 |
| Abstract | The HIV infection is characterized by the existence of a clinical latency period (os asymptomatic period) between the acute infection and the AIDS phase, whose duration is extremely variable, generating distinct progression profiles between Hiv infected individuals. A small fraction of infected individuals (5-10%), named long term non progressors (LTNP), remains clinically asymptomatic and with high TCD4+ levels (>500cells/ul) during more than 8 years of infection in absence of treatment. Some of these individuals can even block almost all the viral replication and evolution, generating an evolutionary latency. The objective of this study was to analyze the mutational profile of HIV-1 and the emergency and maintenance dynamic of immune response escape mutants in HIV-1 positive patients classified as LTNPs and with different levels of viral replication control. For this end, a group of 12 LTNP patients, classified as viremic controllers (VC) and Elite Controllers with (ECB) and without Blips (EC) according to their level of viremia control, was used. For each individual, DNA samples were extracted from PBMCs obtained during the earliest (V1) and most recent visits (VX) available. The extracted DNA was used to amplification and sequencing, through a NGS methodology, of the Gag and Nef genes. The sequences obtained allowed to map the whole Nef gene (medium coverage of 286.463 reads/pb) and the first 1000bps of Gag (medium coverage of 212.674 reads/pb) The consensus sequences of each mapping were used to divergence analyses between V1 and VX and variants with frequencies higher than 0,5% in each mapped bp were considered real. The evolution analyses showed a lower degree of diversity and divergence of Gag and Nef genes between controllers. EC individuals presented lower mutational profile in both genes when compared with ECB and VC patients. While Gag presented higher conservation than Nef in VCs, both genes had showed similar variability in ECs, indicating that a higher viremia control limit the evolution in both regions. In some ECB individuals, evidence of superinfection and APOBEC3g mediated Hypermutation was observed. The analyses of mutation along regions of CTL-restricted epitopes had showed the presence of mutations arised between V1 and VX, which were indicative of imune response escape, in most individuals. Non synonymous mutations had been found in lower frequencies in all individuals, including ECs, indicating that those escape variantes arise, but most don\2019t manage to obtain evolutionary success |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://www.arca.fiocruz.br/bitstream/icict/15377/2/diogo_caetano_ioc_mest_2016.pdf |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
