HIV-1 envelope glycoproteins isolated from Viremic Non-Progressor individuals are fully functional and cytopathic
| Autor: | Lucile Espert, Daniel Márquez-Arce, Bonaventura Clotet, Judith Estévez-Herrera, Romina Cabrera-Rodríguez, Isabel Olivares, Martine Biard-Piechaczyk, Cecilio López-Galíndez, Cecilia Cabrera, Veronique Hebmann, Agustín Valenzuela-Fernández, Silvia Marfil, Silvia Pérez-Yanes, Maria Pernas, Victor Urrea, Concepción Casado, Sara Marrero-Hernández, Julià Blanco |
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| Přispěvatelé: | Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM), Centre National de la Recherche Scientifique (CNRS), Red de Investigación Cooperativa en Investigación en Sida (España), Instituto de Salud Carlos III, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Ministerio de Economía y Competitividad (España), Agencia Canaria de investigación, Innovación y Sociedad de la Información, Universidad de La Laguna [Tenerife - SP] (ULL), IrsiCaixa (Institut de Recerca de la Sida), Centro Nacional de Microbiología [ISCIII, Madrid, Spain] (CNM), Instituto de Salud Carlos III [Madrid] (ISC), Universitat de Vic, Agencia Canaria de Investigación, Innovación y Sociedad de la Información |
| Rok vydání: | 2019 |
| Předmět: |
CD4-Positive T-Lymphocytes
0301 basic medicine [SDV]Life Sciences [q-bio] viruses lcsh:Medicine HIV Infections Índice de masa corporal Virus Replication Diabetes mellitus 0302 clinical medicine lcsh:Science ComputingMilieux_MISCELLANEOUS chemistry.chemical_classification Infectivity Multidisciplinary Nutrición enteral domiciliaria env Gene Products Human Immunodeficiency Virus virus diseases 3. Good health [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology medicine.anatomical_structure Antidiabéticos orales CD4 Antigens [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology Viral load Gene Expression Regulation Viral T cell Viremia Biology Article 03 medical and health sciences Glycoprotein complex Autophagy medicine Humans lcsh:R medicine.disease Virology Gastrostomía endoscópica percutánea HEK293 Cells 030104 developmental biology chemistry Viral replication Nutrición enteral HIV-1 lcsh:Q Glycoprotein 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports Scientific Reports, Nature Publishing Group, 2019, 9 (1), ⟨10.1038/s41598-019-42075-3⟩ Repisalud Instituto de Salud Carlos III (ISCIII) Scientific Reports, Nature Publishing Group, 2019, 9, pp.5544. ⟨10.1038/s41598-019-42075-3⟩ r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol instname Scientific Reports, Vol 9, Iss 1, Pp 1-12 (2019) |
| ISSN: | 2045-2322 |
| Popis: | In untreated HIV-1-infected individuals, viremia is positively associated with disease progression. However, some viremic non progressors (VNPs) individuals show paradoxical high CD4+ T cell counts. HIV-1 envelope glycoprotein complex (Env) is a major cytopathic determinant in viral replication; therefore, we have deeply characterized Env function in this rare clinical phenotype. Full-length Env clones isolated from individuals with Viral Load (VL) > 10,000 copies/mL classified as VNPs (n = 15) or rapid progressors (RPs, n = 17) were geno- and phenotypically analyzed by determining diversity, expression, CD4 binding/signaling, fusogenicity, infectivity and autophagy induction. Selected Env clones from VNPs and RPs (n = 32) showed similar expression, fusion and infection abilities. Env clones from both groups showed similar affinity for CD4 during cell-to-cell transmission and consistently induced similar levels of CD4 signaling, measured by α-tubulin acetylation. Moreover, we demonstrate for the first time that primary Env clones from VNP and RP induce autophagy in uninfected cells and that this feature correlated with fusogenic capacity but was unrelated to disease progression. In conclusion, our data suggest that Env clones from VNP individuals are fully functional. Therefore, the paradoxical CD4+ T cell count stability coexisting with high levels of viral replication is unrelated to Env function. This work is supported by Spanish AIDS network “Red Temática Cooperativa de Investigación en SIDA” RD12/0017/0002, RD12/0017/0028, RD12/0017/0034, RD16/0025/0011, RD16/0025/00XX and RD16/0025/0041 as part of the Plan Nacional R + D+ I and cofunded by Spanish “Instituto de Salud Carlos III (ISCIII)-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER)”. Work in JB’s lab is supported by the Spanish Ministry of Health Project Number EC11-043 (to JB and AV-F), by the CNRS PICS program (to MB-P), J.B. and C.C. are researchers from Fundació Institut de Recerca en Ciències de la Salut Germans Trias i Pujol supported by the Health Department of the Catalan Government/Generalitat de Catalunya and ISCIII grant numbers PI14/01307 (to JB) and PI15/01053 (to CC). Work in CL-G’s lab was supported by grants SAF (2010-17226) and (2016-77894-R) from MINECO (Spain) and FIS (PI 13/02269, ISCIII). A.V-F’s Lab is supported by the European Regional Development Fund (ERDF), SAF2015-64118-R (MINECO, Spain) “Fundación CajaCanarias” BIO29, UNLL10-3E-783 (ERDF and “Fundación CajaCanarias”). D.M-A and S.M-H are funded by Fundación CajaCanarias BIO29, SAF2011-24671-FPI, “TESIS2017010116- and TESIS2015-010038-Programa Predoctoral de Formación del Personal Investigador, Agencia Canaria de Investigación, Innovación y Sociedad de la Información” and European Social Fund-fellowships. R.C-R is funded by RIS-RETIC RD16/0025/0011 and J.E-H is funded by the Cabildo Tenerife “Agustin de Betancourt” 2017 Program. Sí |
| Databáze: | OpenAIRE |
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