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Adaptive changes in HIV-1 subtype C proteins during early infection are driven by changes in HLA-associated immune pressure

Florette K. Treurnicht; Cathal Seoighe; Darren P. Martin; Melissa-Rose Abrahams; Debra de Assis Rosa; Helba Bredell; Zenda Woodman; Winston Hide; Koleka P. Mlisana; Salim Abdool Karim; Clive M. Gray; Carolyn Williamson

Title:
Adaptive changes in HIV-1 subtype C proteins during early infection are driven by changes in HLA-associated immune pressure
Author(s):
Treurnicht, Florette K.
Seoighe, Cathal
Martin, Darren P.
Abrahams, Melissa-Rose
Assis Rosa, Debra de
Bredell, Helba
Woodman, Zenda
Hide, Winston
Mlisana, Koleka P.
Abdool Karim, Salim
Gray, Clive M.
Williamson, Carolyn
Date:
Type:
Articles
Department:
Epidemiology
Volume:
396
Permanent URL:
Book/Journal Title:
Virology
Abstract:
It is unresolved whether recently transmitted human immunodeficiency viruses (HIV) have genetic features that specifically favour their transmissibility. To identify potential "transmission signatures", we compared 20 full-length HIV-1 subtype C genomes from primary infections, with 66 sampled from ethnically and geographically matched individuals with chronic infections. Controlling for recombination and phylogenetic relatedness, we identified 39 sites at which amino acid frequency spectra differed significantly between groups. These sites were predominantly located within Env, Pol and Gag (14/39, 9/39 and 6/39 respectively) and were significantly clustered (33/39) within known immunoreactive peptides. Within 6 months of infection, we detected reversion-to-consensus mutations at 14 sites and potential CTL escape mutations at seven. Here we provide evidence that frequent reversion mutations probably allows the virus to recover replicative fitness which, together with immune escape driven by the HLA alleles of the new hosts, differentiate sequences from chronic infections from those sampled shortly after transmission.
Subject(s):
Virology
Epidemiology
Publisher DOI:
http://dx.doi.org/10.1016/j.virol.2009.10.002
Item views:
121
Metadata:
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