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HIV-1 envelope glycoproteins isolated from Viremic Non-Progressor individuals are fully functional and cytopathic.

ABSTRACT: 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 ?-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.

SUBMITTER: Cabrera-Rodriguez R

PROVIDER: S-EPMC6447548 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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HIV-1 envelope glycoproteins isolated from Viremic Non-Progressor individuals are fully functional and cytopathic.

Cabrera-Rodríguez Romina R Hebmann Veronique V Marfil Silvia S Pernas María M Marrero-Hernández Sara S Cabrera Cecilia C Urrea Victor V Casado Concepción C Olivares Isabel I Márquez-Arce Daniel D Pérez-Yanes Silvia S Estévez-Herrera Judith J Clotet Bonaventura B Espert Lucile L López-Galíndez Cecilio C Biard-Piechaczyk Martine M Valenzuela-Fernández Agustín A Blanco Julià J

Scientific reports 20190403 1

In untreated HIV-1-infected individuals, viremia is positively associated with disease progression. However, some viremic non progressors (VNPs) individuals show paradoxical high CD4<sup>+</sup> 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 VNP ...[more]

PMID: 30944395

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Project description:We assessed correlates of protection from disease progression in a rare subset of HIV-infected individuals, viremic non-progressors (VNPs). These individuals have high viral load for several years, but in contrast to the majority of infected individuals, they do not progress to AIDS. Here we found this lack of progression was associated with selective preservation of two essential subsets of memory CD4+ T cells, central memory (TCM) and stem-cell memory (TSCM) cells. Compared to HIV-infected putative progressors, VNPs had higher proliferation of these indispensable subsets of memory cells, which was associated with the number of TCM. In addition, the long-lived CD4+ TCM and TSCM cells in VNPs had decreased HIV infection compared to the less critical effector memory CD4+ T cells, which indicates a possible mechanism by which VNPs maintain their CD4+ T cell pool after several years of infection, and remain free from AIDS progression. 6 HIV-infected patients fitting the clinical criteria of Viremic Non-Progressors were identified. VNPs were defined as having confirmed HIV-1 infection for at least 9 years with sustained plasma HIV RNA levels >10,000 copies/ml and maintenance of peripheral blood CD4+ T cell counts >500 cells/mm3 and a CD4% (of all lymphocytes) >15%. As controls, 7 HIV-infected Putative Progressors were identified. PPs were defined as having plasma HIV RNA levels >10,000 copies/mL, CD4+ T cell counts >400 cells/mm3 and having been initially infected with HIV 2-24 months prior to the index visit. The estimated date of initial HIV infection was calculated according to published algorithms that incorporate âde-tunedâ anti-HIV-1 antibody ELISA results or by a documented sero-conversion window of <6 months. All participants were required to be antiretroviral therapy (ART)-naÃ¯ve. RNA from 6 VNP and 7 PPs was purified from PAXgene whole blood tubes and hybridized to Affymetrix U133 Plus 2.0 arrays. During data analysis, one VNP patient (PID 4015) was determined to be an outlier and removed from further analysis. Thus, 5 VNPs and 7 PPs are represented in this Series.

Dataset Information

HIV-1 envelope glycoproteins isolated from Viremic Non-Progressor individuals are fully functional and cytopathic.

Publications

HIV-1 envelope glycoproteins isolated from Viremic Non-Progressor individuals are fully functional and cytopathic.

Similar Datasets

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