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

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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

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.
Originalspråkengelska
Sidor (från-till)125-134
TidskriftVirology
Volym379
Nummer1
DOI
StatusPublished - 2008

Ämnesklassifikation (UKÄ)

  • Mikrobiologi inom det medicinska området

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