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

Repits, Johanna LU ; Sterjovski, Jasminka; Badia-Martinez, Daniel; Mild, Mattias LU ; Gray, Lachlan; Churchill, Melissa J; Purcell, Damian F J; Karlsson, Anders; Albert, Jan and Fenyö, Eva Maria LU , et al. (2008) In Virology 379(1). p.125-134
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Virology
volume
379
issue
1
pages
125 - 134
publisher
Elsevier
external identifiers
  • WOS:000259100900014
  • PMID:18672260
  • Scopus:48949086689
ISSN
1096-0341
DOI
10.1016/j.virol.2008.06.014
language
English
LU publication?
yes
id
1aa18e42-7c4b-410d-94db-0143491bfbea (old id 1223575)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18672260?dopt=Abstract
date added to LUP
2008-09-10 12:01:15
date last changed
2016-10-13 04:29:07
@misc{1aa18e42-7c4b-410d-94db-0143491bfbea,
  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.},
  author       = {Repits, Johanna and Sterjovski, Jasminka and Badia-Martinez, Daniel and Mild, Mattias and Gray, Lachlan and Churchill, Melissa J and Purcell, Damian F J and Karlsson, Anders and Albert, Jan and Fenyö, Eva Maria and Achour, Adnane and Gorry, Paul R and Jansson, Marianne},
  issn         = {1096-0341},
  language     = {eng},
  number       = {1},
  pages        = {125--134},
  publisher    = {ARRAY(0x99edb18)},
  series       = {Virology},
  title        = {Primary HIV-1 R5 isolates from end-stage disease display enhanced viral fitness in parallel with increased gp120 net charge.},
  url          = {http://dx.doi.org/10.1016/j.virol.2008.06.014},
  volume       = {379},
  year         = {2008},
}