Viral Characteristics Associated with the Clinical Nonprogressor Phenotype Are Inherited by Viruses from a Cluster of HIV-1 Elite Controllers

ABSTRACT A small group of HIV-1-infected individuals, called long-term nonprogressors (LTNPs), and in particular a subgroup of LTNPs, elite controllers (LTNP-ECs), display permanent control of viral replication and lack of clinical progression. This control is the result of a complex interaction of...

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Autores principales:	Concepción Casado, Sara Marrero-Hernández, Daniel Márquez-Arce, María Pernas, Sílvia Marfil, Ferran Borràs-Grañana, Isabel Olivares, Romina Cabrera-Rodríguez, María-Soledad Valera, Laura de Armas-Rillo, Philippe Lemey, Julià Blanco, Agustín Valenzuela-Fernández, Cecilio Lopez-Galíndez
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	CD4 binding HIV-1 heritability LTNP-EC actin-tubulin modifications cell signaling Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b9c065f676794e36920b4671b9e28c10
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spelling	oai:doaj.org-article:b9c065f676794e36920b4671b9e28c102021-11-15T15:53:26ZViral Characteristics Associated with the Clinical Nonprogressor Phenotype Are Inherited by Viruses from a Cluster of HIV-1 Elite Controllers10.1128/mBio.02338-172150-7511https://doaj.org/article/b9c065f676794e36920b4671b9e28c102018-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02338-17https://doaj.org/toc/2150-7511ABSTRACT A small group of HIV-1-infected individuals, called long-term nonprogressors (LTNPs), and in particular a subgroup of LTNPs, elite controllers (LTNP-ECs), display permanent control of viral replication and lack of clinical progression. This control is the result of a complex interaction of host, immune, and viral factors. We identified, by phylogenetic analysis, a cluster of LTNP-ECs infected with very similar low-replication HIV-1 viruses, suggesting the contribution of common viral features to the clinical LTNP-EC phenotype. HIV-1 envelope (Env) glycoprotein mediates signaling and promotes HIV-1 fusion, entry, and infection, being a key factor of viral fitness in vitro, cytopathicity, and infection progression in vivo. Therefore, we isolated full-length env genes from viruses of these patients and from chronically infected control individuals. Functional characterization of the initial events of the viral infection showed that Envs from the LTNP-ECs were ineffective in the binding to CD4 and in the key triggering of actin/tubulin-cytoskeleton modifications compared to Envs from chronic patients. The viral properties of the cluster viruses result in a defective viral fusion, entry, and infection, and these properties were inherited by every virus of the cluster. Therefore, inefficient HIV-1 Env functions and signaling defects may contribute to the low viral replication capacity and transmissibility of the cluster viruses, suggesting a direct role in the LTNP-EC phenotype of these individuals. These results highlight the important role of viral characteristics in the LTNP-EC clinical phenotype. These Env viral properties were common to all the cluster viruses and thus support the heritability of the viral characteristics. IMPORTANCE HIV-1 long-term nonprogressor elite controller patients, due to their permanent control of viral replication, have been the object of numerous studies to identify the factors responsible for this clinical phenotype. In this work, we analyzed the viral characteristics of the envelopes of viruses from a phylogenetic cluster of LTNP-EC patients. These envelopes showed ineffective binding to CD4 and the subsequent signaling activity to modify actin/tubulin cytoskeletons, which result in low fusion and deficient entry and infection capacities. These Env viral characteristics could explain the nonprogressor clinical phenotype of these patients. In addition, these inefficient env viral properties were present in all viruses of the cluster, supporting the heritability of the viral phenotype.Concepción CasadoSara Marrero-HernándezDaniel Márquez-ArceMaría PernasSílvia MarfilFerran Borràs-GrañanaIsabel OlivaresRomina Cabrera-RodríguezMaría-Soledad ValeraLaura de Armas-RilloPhilippe LemeyJulià BlancoAgustín Valenzuela-FernándezCecilio Lopez-GalíndezAmerican Society for MicrobiologyarticleCD4 bindingHIV-1heritabilityLTNP-ECactin-tubulin modificationscell signalingMicrobiologyQR1-502ENmBio, Vol 9, Iss 2 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	CD4 binding HIV-1 heritability LTNP-EC actin-tubulin modifications cell signaling Microbiology QR1-502
spellingShingle	CD4 binding HIV-1 heritability LTNP-EC actin-tubulin modifications cell signaling Microbiology QR1-502 Concepción Casado Sara Marrero-Hernández Daniel Márquez-Arce María Pernas Sílvia Marfil Ferran Borràs-Grañana Isabel Olivares Romina Cabrera-Rodríguez María-Soledad Valera Laura de Armas-Rillo Philippe Lemey Julià Blanco Agustín Valenzuela-Fernández Cecilio Lopez-Galíndez Viral Characteristics Associated with the Clinical Nonprogressor Phenotype Are Inherited by Viruses from a Cluster of HIV-1 Elite Controllers
description	ABSTRACT A small group of HIV-1-infected individuals, called long-term nonprogressors (LTNPs), and in particular a subgroup of LTNPs, elite controllers (LTNP-ECs), display permanent control of viral replication and lack of clinical progression. This control is the result of a complex interaction of host, immune, and viral factors. We identified, by phylogenetic analysis, a cluster of LTNP-ECs infected with very similar low-replication HIV-1 viruses, suggesting the contribution of common viral features to the clinical LTNP-EC phenotype. HIV-1 envelope (Env) glycoprotein mediates signaling and promotes HIV-1 fusion, entry, and infection, being a key factor of viral fitness in vitro, cytopathicity, and infection progression in vivo. Therefore, we isolated full-length env genes from viruses of these patients and from chronically infected control individuals. Functional characterization of the initial events of the viral infection showed that Envs from the LTNP-ECs were ineffective in the binding to CD4 and in the key triggering of actin/tubulin-cytoskeleton modifications compared to Envs from chronic patients. The viral properties of the cluster viruses result in a defective viral fusion, entry, and infection, and these properties were inherited by every virus of the cluster. Therefore, inefficient HIV-1 Env functions and signaling defects may contribute to the low viral replication capacity and transmissibility of the cluster viruses, suggesting a direct role in the LTNP-EC phenotype of these individuals. These results highlight the important role of viral characteristics in the LTNP-EC clinical phenotype. These Env viral properties were common to all the cluster viruses and thus support the heritability of the viral characteristics. IMPORTANCE HIV-1 long-term nonprogressor elite controller patients, due to their permanent control of viral replication, have been the object of numerous studies to identify the factors responsible for this clinical phenotype. In this work, we analyzed the viral characteristics of the envelopes of viruses from a phylogenetic cluster of LTNP-EC patients. These envelopes showed ineffective binding to CD4 and the subsequent signaling activity to modify actin/tubulin cytoskeletons, which result in low fusion and deficient entry and infection capacities. These Env viral characteristics could explain the nonprogressor clinical phenotype of these patients. In addition, these inefficient env viral properties were present in all viruses of the cluster, supporting the heritability of the viral phenotype.
format	article
author	Concepción Casado Sara Marrero-Hernández Daniel Márquez-Arce María Pernas Sílvia Marfil Ferran Borràs-Grañana Isabel Olivares Romina Cabrera-Rodríguez María-Soledad Valera Laura de Armas-Rillo Philippe Lemey Julià Blanco Agustín Valenzuela-Fernández Cecilio Lopez-Galíndez
author_facet	Concepción Casado Sara Marrero-Hernández Daniel Márquez-Arce María Pernas Sílvia Marfil Ferran Borràs-Grañana Isabel Olivares Romina Cabrera-Rodríguez María-Soledad Valera Laura de Armas-Rillo Philippe Lemey Julià Blanco Agustín Valenzuela-Fernández Cecilio Lopez-Galíndez
author_sort	Concepción Casado
title	Viral Characteristics Associated with the Clinical Nonprogressor Phenotype Are Inherited by Viruses from a Cluster of HIV-1 Elite Controllers
title_short	Viral Characteristics Associated with the Clinical Nonprogressor Phenotype Are Inherited by Viruses from a Cluster of HIV-1 Elite Controllers
title_full	Viral Characteristics Associated with the Clinical Nonprogressor Phenotype Are Inherited by Viruses from a Cluster of HIV-1 Elite Controllers
title_fullStr	Viral Characteristics Associated with the Clinical Nonprogressor Phenotype Are Inherited by Viruses from a Cluster of HIV-1 Elite Controllers
title_full_unstemmed	Viral Characteristics Associated with the Clinical Nonprogressor Phenotype Are Inherited by Viruses from a Cluster of HIV-1 Elite Controllers
title_sort	viral characteristics associated with the clinical nonprogressor phenotype are inherited by viruses from a cluster of hiv-1 elite controllers
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/b9c065f676794e36920b4671b9e28c10
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Viral Characteristics Associated with the Clinical Nonprogressor Phenotype Are Inherited by Viruses from a Cluster of HIV-1 Elite Controllers

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