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CRF19_cpx is an Evolutionary fit HIV-1 Variant Strongly Associated With Rapid Progression to AIDS in Cuba

BACKGROUND: Clinicians reported an increasing trend of rapid progression (RP) (AIDS within 3 years of infection) in Cuba. METHODS: Recently infected patients were prospectively sampled, 52 RP at AIDS diagnosis (AIDS-RP) and 21 without AIDS in the same time frame (non-AIDS). 22 patients were sampled...

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Autores principales: Kouri, Vivian, Khouri, Ricardo, Alemán‬, Yoan, Abrahantes, Yeissel, Vercauteren, Jurgen, Pineda-Peña, Andrea-Clemencia, Theys, Kristof, Megens, Sarah, Moutschen, Michel, Pfeifer, Nico, Van Weyenbergh, Johan, Pérez, Ana B., Pérez, Jorge, Pérez, Lissette, Van Laethem, Kristel, Vandamme, Anne-Mieke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4484819/
https://www.ncbi.nlm.nih.gov/pubmed/26137563
http://dx.doi.org/10.1016/j.ebiom.2015.01.015
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author Kouri, Vivian
Khouri, Ricardo
Alemán‬, Yoan
Abrahantes, Yeissel
Vercauteren, Jurgen
Pineda-Peña, Andrea-Clemencia
Theys, Kristof
Megens, Sarah
Moutschen, Michel
Pfeifer, Nico
Van Weyenbergh, Johan
Pérez, Ana B.
Pérez, Jorge
Pérez, Lissette
Van Laethem, Kristel
Vandamme, Anne-Mieke
author_facet Kouri, Vivian
Khouri, Ricardo
Alemán‬, Yoan
Abrahantes, Yeissel
Vercauteren, Jurgen
Pineda-Peña, Andrea-Clemencia
Theys, Kristof
Megens, Sarah
Moutschen, Michel
Pfeifer, Nico
Van Weyenbergh, Johan
Pérez, Ana B.
Pérez, Jorge
Pérez, Lissette
Van Laethem, Kristel
Vandamme, Anne-Mieke
author_sort Kouri, Vivian
collection PubMed
description BACKGROUND: Clinicians reported an increasing trend of rapid progression (RP) (AIDS within 3 years of infection) in Cuba. METHODS: Recently infected patients were prospectively sampled, 52 RP at AIDS diagnosis (AIDS-RP) and 21 without AIDS in the same time frame (non-AIDS). 22 patients were sampled at AIDS diagnosis (chronic-AIDS) retrospectively assessed as > 3 years infected. Clinical, demographic, virological, epidemiological and immunological data were collected. Pol and env sequences were used for subtyping, transmission cluster analysis, and prediction of resistance, co-receptor use and evolutionary fitness. Host, immunological and viral predictors of RP were explored through data mining. FINDINGS: Subtyping revealed 26 subtype B strains, 6 C, 6 CRF18_cpx, 9 CRF19_cpx, 29 BG-recombinants and other subtypes/URFs. All patients infected with CRF19 belonged to the AIDS-RP group. Data mining identified CRF19, oral candidiasis and RANTES levels as the strongest predictors of AIDS-RP. CRF19 was more frequently predicted to use the CXCR4 co-receptor, had higher fitness scores in the protease region, and patients had higher viral load at diagnosis. INTERPRETATION: CRF19 is a recombinant of subtype D (C-part of Gag, PR, RT and nef), subtype A (N-part of Gag, Integrase, Env) and subtype G (Vif, Vpr, Vpu and C-part of Env). Since subtypes D and A have been associated with respectively faster and slower disease progression, our findings might indicate a fit PR driving high viral load, which in combination with co-infections may boost RANTES levels and thus CXCR4 use, potentially explaining the fast progression. We propose that CRF19 is evolutionary very fit and causing rapid progression to AIDS in many newly infected patients in Cuba.
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spelling pubmed-44848192015-07-01 CRF19_cpx is an Evolutionary fit HIV-1 Variant Strongly Associated With Rapid Progression to AIDS in Cuba Kouri, Vivian Khouri, Ricardo Alemán‬, Yoan Abrahantes, Yeissel Vercauteren, Jurgen Pineda-Peña, Andrea-Clemencia Theys, Kristof Megens, Sarah Moutschen, Michel Pfeifer, Nico Van Weyenbergh, Johan Pérez, Ana B. Pérez, Jorge Pérez, Lissette Van Laethem, Kristel Vandamme, Anne-Mieke EBioMedicine Original Article BACKGROUND: Clinicians reported an increasing trend of rapid progression (RP) (AIDS within 3 years of infection) in Cuba. METHODS: Recently infected patients were prospectively sampled, 52 RP at AIDS diagnosis (AIDS-RP) and 21 without AIDS in the same time frame (non-AIDS). 22 patients were sampled at AIDS diagnosis (chronic-AIDS) retrospectively assessed as > 3 years infected. Clinical, demographic, virological, epidemiological and immunological data were collected. Pol and env sequences were used for subtyping, transmission cluster analysis, and prediction of resistance, co-receptor use and evolutionary fitness. Host, immunological and viral predictors of RP were explored through data mining. FINDINGS: Subtyping revealed 26 subtype B strains, 6 C, 6 CRF18_cpx, 9 CRF19_cpx, 29 BG-recombinants and other subtypes/URFs. All patients infected with CRF19 belonged to the AIDS-RP group. Data mining identified CRF19, oral candidiasis and RANTES levels as the strongest predictors of AIDS-RP. CRF19 was more frequently predicted to use the CXCR4 co-receptor, had higher fitness scores in the protease region, and patients had higher viral load at diagnosis. INTERPRETATION: CRF19 is a recombinant of subtype D (C-part of Gag, PR, RT and nef), subtype A (N-part of Gag, Integrase, Env) and subtype G (Vif, Vpr, Vpu and C-part of Env). Since subtypes D and A have been associated with respectively faster and slower disease progression, our findings might indicate a fit PR driving high viral load, which in combination with co-infections may boost RANTES levels and thus CXCR4 use, potentially explaining the fast progression. We propose that CRF19 is evolutionary very fit and causing rapid progression to AIDS in many newly infected patients in Cuba. Elsevier 2015-01-28 /pmc/articles/PMC4484819/ /pubmed/26137563 http://dx.doi.org/10.1016/j.ebiom.2015.01.015 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Kouri, Vivian
Khouri, Ricardo
Alemán‬, Yoan
Abrahantes, Yeissel
Vercauteren, Jurgen
Pineda-Peña, Andrea-Clemencia
Theys, Kristof
Megens, Sarah
Moutschen, Michel
Pfeifer, Nico
Van Weyenbergh, Johan
Pérez, Ana B.
Pérez, Jorge
Pérez, Lissette
Van Laethem, Kristel
Vandamme, Anne-Mieke
CRF19_cpx is an Evolutionary fit HIV-1 Variant Strongly Associated With Rapid Progression to AIDS in Cuba
title CRF19_cpx is an Evolutionary fit HIV-1 Variant Strongly Associated With Rapid Progression to AIDS in Cuba
title_full CRF19_cpx is an Evolutionary fit HIV-1 Variant Strongly Associated With Rapid Progression to AIDS in Cuba
title_fullStr CRF19_cpx is an Evolutionary fit HIV-1 Variant Strongly Associated With Rapid Progression to AIDS in Cuba
title_full_unstemmed CRF19_cpx is an Evolutionary fit HIV-1 Variant Strongly Associated With Rapid Progression to AIDS in Cuba
title_short CRF19_cpx is an Evolutionary fit HIV-1 Variant Strongly Associated With Rapid Progression to AIDS in Cuba
title_sort crf19_cpx is an evolutionary fit hiv-1 variant strongly associated with rapid progression to aids in cuba
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4484819/
https://www.ncbi.nlm.nih.gov/pubmed/26137563
http://dx.doi.org/10.1016/j.ebiom.2015.01.015
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