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Frontiers in microbiology
2022;13 763039.

The Characteristics of the HIV-1 Env Glycoprotein Are Linked With Viral Pathogenesis.

Silvia Pérez-Yanes, María Pernas, Silvia Marfil, Romina Cabrera-Rodríguez, Raquel Ortiz, Víctor Urrea, Carla Rovirosa, Judith Estévez-Herrera, Isabel Olivares, Concepción Casado, Cecilio Lopez-Galindez, Julià Blanco, Agustín Valenzuela-Fernández
Author Information
  1. Silvia Pérez-Yanes: Unidad de Farmacología, Sección de Medicina, Laboratorio de Inmunología Celular y Viral, Facultad de Ciencias de la Salud de la Universidad de La Laguna (ULL), San Cristóbal de La Laguna, Spain.
  2. María Pernas: Unidad de Virologia Molecular, Laboratorio de Referencia e Investigación en Retrovirus, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Madrid, Spain.
  3. Silvia Marfil: Institut de Recerca de la Sida IrsiCaixa, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Barcelona, Spain.
  4. Romina Cabrera-Rodríguez: Unidad de Farmacología, Sección de Medicina, Laboratorio de Inmunología Celular y Viral, Facultad de Ciencias de la Salud de la Universidad de La Laguna (ULL), San Cristóbal de La Laguna, Spain.
  5. Raquel Ortiz: Institut de Recerca de la Sida IrsiCaixa, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Barcelona, Spain.
  6. Víctor Urrea: Institut de Recerca de la Sida IrsiCaixa, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Barcelona, Spain.
  7. Carla Rovirosa: Institut de Recerca de la Sida IrsiCaixa, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Barcelona, Spain.
  8. Judith Estévez-Herrera: Unidad de Farmacología, Sección de Medicina, Laboratorio de Inmunología Celular y Viral, Facultad de Ciencias de la Salud de la Universidad de La Laguna (ULL), San Cristóbal de La Laguna, Spain.
  9. Isabel Olivares: Unidad de Virologia Molecular, Laboratorio de Referencia e Investigación en Retrovirus, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Madrid, Spain.
  10. Concepción Casado: Unidad de Virologia Molecular, Laboratorio de Referencia e Investigación en Retrovirus, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Madrid, Spain.
  11. Cecilio Lopez-Galindez: Unidad de Virologia Molecular, Laboratorio de Referencia e Investigación en Retrovirus, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Madrid, Spain.
  12. Julià Blanco: Institut de Recerca de la Sida IrsiCaixa, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Barcelona, Spain.
  13. Agustín Valenzuela-Fernández: Unidad de Farmacología, Sección de Medicina, Laboratorio de Inmunología Celular y Viral, Facultad de Ciencias de la Salud de la Universidad de La Laguna (ULL), San Cristóbal de La Laguna, Spain.
PMID: 35401460 DOI: 10.3389/fmicb.2022.763039

Abstract

The understanding of HIV-1 pathogenesis and clinical progression is incomplete due to the variable contribution of host, immune, and viral factors. The involvement of viral factors has been investigated in extreme clinical phenotypes from rapid progressors to long-term non-progressors (LTNPs). Among HIV-1 proteins, the envelope glycoprotein complex (Env) has been concentrated on in many studies for its important role in the immune response and in the first steps of viral replication. In this study, we analyzed the contribution of 41 Envs from 24 patients with different clinical progression rates and viral loads (VLs), LTNP-Elite Controllers (LTNP-ECs); Viremic LTNPs (vLTNPs), and non-controller individuals contemporary to LTNPs or recent, named Old and Modern progressors. We studied the Env expression, the fusion and cell-to-cell transfer capacities, as well as viral infectivity. The sequence and phylogenetic analysis of Envs were also performed. In every functional characteristic, the Envs from subjects with viral control (LTNP-ECs and vLTNPs) showed significant lower performance compared to those from the progressor individuals (Old and Modern). Regarding sequence analysis, the variable loops of the gp120 subunit of the Env (i.e., V2, V4, and mainly V5) of the progressor individuals showed longer and more glycosylated sequences than controller subjects. Therefore, HIV-1 Envs from virus of patients presenting viremic control and the non-progressor clinical phenotype showed poor viral functions and shorter sequences, whereas functional Envs were associated with virus of patients lacking virological control and with progressor clinical phenotypes. These correlations support the role of Env genotypic and phenotypic characteristics in the HIV-1 infection and pathogenesis.

Keywords

HIV elite controllers (HIV-1 EC) functional defect functional envelope lack of virological control viral envelope

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