Primary HIV-1 R5 isolates from end-stage disease display enhanced viral fitness in parallel with increased gp120 net charge.

Research output: Contribution to journalArticle

Abstract

To better understand the evolution of the viral envelope glycoproteins (Env) in HIV-1 infected individuals who progress to AIDS maintaining an exclusive CCR5-using (R5) virus population, we cloned and sequenced the env gene of longitudinally obtained primary isolates. A shift in the electrostatic potential towards an increased net positive charge was revealed in gp120 of end-stage viruses. Residues with increased positive charge were primarily localized in the gp120 variable regions, with the exception of the V3 loop. Molecular modeling indicated that the modifications clustered on the gp120 surface. Furthermore, correlations between increased Env net charge and lowered CD4(+) T cell counts, enhanced viral fitness, reduced sensitivity to entry inhibitors and augmented cell attachment were disclosed. In summary, this study suggests that R5 HIV-1 variants with increased gp120 net charge emerge in an opportunistic manner during severe immunodeficiency. Thus, we here propose a new mechanism by which HIV-1 may gain fitness.

Details

Authors
  • Johanna Repits
  • Jasminka Sterjovski
  • Daniel Badia-Martinez
  • Mattias Mild
  • Lachlan Gray
  • Melissa J Churchill
  • Damian F J Purcell
  • Anders Karlsson
  • Jan Albert
  • Eva Maria Fenyö
  • Adnane Achour
  • Paul R Gorry
  • Marianne Jansson
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Microbiology in the medical area
Original languageEnglish
Pages (from-to)125-134
JournalVirology
Volume379
Issue number1
Publication statusPublished - 2008
Publication categoryResearch
Peer-reviewedYes

Related research output

Johanna Repits, 2008, Department of Laboratory Medicine, Lund University. 120 p.

Research output: ThesisDoctoral Thesis (compilation)

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