Journal
VIROLOGY
Volume 379, Issue 1, Pages 125-134Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2008.06.014
Keywords
HIV-1; R5; AIDS; Env; gpl20; net charge; evolution; viral fitness
Categories
Funding
- SWEGENE consortium
- Swedish Research Council
- Swedish international Development Agency/Department for Research Cooperation (Sida/SAREC)
- Magn. Bergvall's Foundation
- AIDS Research Foundation
- Clas Groschinskys Foundation
- Royal Physiographic Society ill Lund, Sweden
- Solander Foundation
- Australian National Health and Medical Research Council (NHMRC) [433915]
- Australian NHMRC Dora Lush Biomedical Postgraduate Research
Ask authors/readers for more resources
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 gp 120 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 oil 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. (c) 2008 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available