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

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.

journal_name

Virology

journal_title

Virology

authors

Repits J,Sterjovski J,Badia-Martinez D,Mild M,Gray L,Churchill MJ,Purcell DF,Karlsson A,Albert J,Fenyö EM,Achour A,Gorry PR,Jansson M

doi

10.1016/j.virol.2008.06.014

subject

Has Abstract

pub_date

2008-09-15 00:00:00

pages

125-34

issue

1

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(08)00409-1

journal_volume

379

pub_type

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