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Highly divergent patterns of genetic diversity and evolution in proviral quasispecies from HIV controllers

BACKGROUND: Ongoing intra-host HIV-1 evolution has been shown in individuals that naturally suppress the viremia to low levels (HIV controllers) by the analysis of the RNA in plasma compartment. Detection of evolution at the DNA proviral compartment in HIV controllers, however, has been more challen...

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Autores principales: de Azevedo, Suwellen S. D., Caetano, Diogo Gama, Côrtes, Fernanda H., Teixeira, Sylvia L. M., dos Santos Silva, Karina, Hoagland, Brenda, Grinsztejn, Beatriz, Veloso, Valdilea G., Morgado, Mariza G., Bello, Gonzalo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414336/
https://www.ncbi.nlm.nih.gov/pubmed/28464889
http://dx.doi.org/10.1186/s12977-017-0354-5
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author de Azevedo, Suwellen S. D.
Caetano, Diogo Gama
Côrtes, Fernanda H.
Teixeira, Sylvia L. M.
dos Santos Silva, Karina
Hoagland, Brenda
Grinsztejn, Beatriz
Veloso, Valdilea G.
Morgado, Mariza G.
Bello, Gonzalo
author_facet de Azevedo, Suwellen S. D.
Caetano, Diogo Gama
Côrtes, Fernanda H.
Teixeira, Sylvia L. M.
dos Santos Silva, Karina
Hoagland, Brenda
Grinsztejn, Beatriz
Veloso, Valdilea G.
Morgado, Mariza G.
Bello, Gonzalo
author_sort de Azevedo, Suwellen S. D.
collection PubMed
description BACKGROUND: Ongoing intra-host HIV-1 evolution has been shown in individuals that naturally suppress the viremia to low levels (HIV controllers) by the analysis of the RNA in plasma compartment. Detection of evolution at the DNA proviral compartment in HIV controllers, however, has been more challenging and the precise correlation between the systemic viral suppression level and rate of reservoir’s reseeding in those individuals is not fully understood. In this sense, we examined the proviral DNA quasispecies by single genome amplification of the env gene in a cohort of 23 HIV controllers from Brazil, divided in three groups, according to the level of systemic viral suppression: (1) elite controllers with persistent undetectable viral load (PEC, n = 6); (2) elite controllers with occasional episodes of transient (51–400 copies/mL) viremia (EEC, n = 7); and (3) viremic controllers with persistent low-level (80–2000 copies/mL) viremia (VC, n = 10). RESULTS: The HIV-1 diversity of the PBMC-associated proviral quasispecies in EC was significantly (P < 0.01) lower than in VC, but not significantly different between PEC and EEC groups. We detected a considerable variation in the average pairwise nucleotide distance and proportion of unique sequences in the HIV-1 proviral quasispecies of PEC and EEC. Some PEC and EEC displayed highly homogenous proviral populations with large clusters of identical sequences, while others exhibited relatively diverse proviral populations with a high proportion of unique sequences comparable to VC subjects. The long-term (10–15 years) follow-up of the HIV-1 proviral populations revealed a complete evolutionary stasis in one PEC and measurable divergence rates in one EEC [3.1 (1.2–5.6) × 10(−3) substitutions/site/year and one VC [2.9 (0.7–5.1) × 10(−3) substitutions/site/year]. CONCLUSIONS: There is no simple relationship between systemic viral suppression and intra-host proviral diversity or rate of reservoir’s reseeding in chronically infected HIV controllers. Our results demonstrate that very divergent patterns of intra-host viral diversity and divergence could be detected in the setting of natural suppression of HIV-1 replication and that ongoing evolution and reseeding of the PBMC proviral reservoir occurs in some elite controllers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-017-0354-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-54143362017-05-03 Highly divergent patterns of genetic diversity and evolution in proviral quasispecies from HIV controllers de Azevedo, Suwellen S. D. Caetano, Diogo Gama Côrtes, Fernanda H. Teixeira, Sylvia L. M. dos Santos Silva, Karina Hoagland, Brenda Grinsztejn, Beatriz Veloso, Valdilea G. Morgado, Mariza G. Bello, Gonzalo Retrovirology Research BACKGROUND: Ongoing intra-host HIV-1 evolution has been shown in individuals that naturally suppress the viremia to low levels (HIV controllers) by the analysis of the RNA in plasma compartment. Detection of evolution at the DNA proviral compartment in HIV controllers, however, has been more challenging and the precise correlation between the systemic viral suppression level and rate of reservoir’s reseeding in those individuals is not fully understood. In this sense, we examined the proviral DNA quasispecies by single genome amplification of the env gene in a cohort of 23 HIV controllers from Brazil, divided in three groups, according to the level of systemic viral suppression: (1) elite controllers with persistent undetectable viral load (PEC, n = 6); (2) elite controllers with occasional episodes of transient (51–400 copies/mL) viremia (EEC, n = 7); and (3) viremic controllers with persistent low-level (80–2000 copies/mL) viremia (VC, n = 10). RESULTS: The HIV-1 diversity of the PBMC-associated proviral quasispecies in EC was significantly (P < 0.01) lower than in VC, but not significantly different between PEC and EEC groups. We detected a considerable variation in the average pairwise nucleotide distance and proportion of unique sequences in the HIV-1 proviral quasispecies of PEC and EEC. Some PEC and EEC displayed highly homogenous proviral populations with large clusters of identical sequences, while others exhibited relatively diverse proviral populations with a high proportion of unique sequences comparable to VC subjects. The long-term (10–15 years) follow-up of the HIV-1 proviral populations revealed a complete evolutionary stasis in one PEC and measurable divergence rates in one EEC [3.1 (1.2–5.6) × 10(−3) substitutions/site/year and one VC [2.9 (0.7–5.1) × 10(−3) substitutions/site/year]. CONCLUSIONS: There is no simple relationship between systemic viral suppression and intra-host proviral diversity or rate of reservoir’s reseeding in chronically infected HIV controllers. Our results demonstrate that very divergent patterns of intra-host viral diversity and divergence could be detected in the setting of natural suppression of HIV-1 replication and that ongoing evolution and reseeding of the PBMC proviral reservoir occurs in some elite controllers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-017-0354-5) contains supplementary material, which is available to authorized users. BioMed Central 2017-05-02 /pmc/articles/PMC5414336/ /pubmed/28464889 http://dx.doi.org/10.1186/s12977-017-0354-5 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
de Azevedo, Suwellen S. D.
Caetano, Diogo Gama
Côrtes, Fernanda H.
Teixeira, Sylvia L. M.
dos Santos Silva, Karina
Hoagland, Brenda
Grinsztejn, Beatriz
Veloso, Valdilea G.
Morgado, Mariza G.
Bello, Gonzalo
Highly divergent patterns of genetic diversity and evolution in proviral quasispecies from HIV controllers
title Highly divergent patterns of genetic diversity and evolution in proviral quasispecies from HIV controllers
title_full Highly divergent patterns of genetic diversity and evolution in proviral quasispecies from HIV controllers
title_fullStr Highly divergent patterns of genetic diversity and evolution in proviral quasispecies from HIV controllers
title_full_unstemmed Highly divergent patterns of genetic diversity and evolution in proviral quasispecies from HIV controllers
title_short Highly divergent patterns of genetic diversity and evolution in proviral quasispecies from HIV controllers
title_sort highly divergent patterns of genetic diversity and evolution in proviral quasispecies from hiv controllers
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414336/
https://www.ncbi.nlm.nih.gov/pubmed/28464889
http://dx.doi.org/10.1186/s12977-017-0354-5
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