High Frequency of Transmitted HIV-1 Gag HLA Class I-Driven Immune Escape Variants but Minimal Immune Selection over the First Year of Clade C Infection
View/ Open
Author
Gounder, Kamini
Padayachi, Nagavelli
Mann, Jaclyn K.
Radebe, Mopo
Mokgoro, Mammekwa
van der Stok, Mary
Mkhize, Lungile
Mncube, Zenele
Jaggernath, Manjeetha
Reddy, Tarylee
Ndung’u, Thumbi
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1371/journal.pone.0119886Metadata
Show full item recordCitation
Gounder, K., N. Padayachi, J. K. Mann, M. Radebe, M. Mokgoro, M. van der Stok, L. Mkhize, et al. 2015. “High Frequency of Transmitted HIV-1 Gag HLA Class I-Driven Immune Escape Variants but Minimal Immune Selection over the First Year of Clade C Infection.” PLoS ONE 10 (3): e0119886. doi:10.1371/journal.pone.0119886. http://dx.doi.org/10.1371/journal.pone.0119886.Abstract
In chronic HIV infection, CD8+ T cell responses to Gag are associated with lower viral loads, but longitudinal studies of HLA-restricted CD8+ T cell-driven selection pressure in Gag from the time of acute infection are limited. In this study we examined Gag sequence evolution over the first year of infection in 22 patients identified prior to seroconversion. A total of 310 and 337 full-length Gag sequences from the earliest available samples (median = 14 days after infection [Fiebig stage I/II]) and at one-year post infection respectively were generated. Six of 22 (27%) individuals were infected with multiple variants. There was a trend towards early intra-patient viral sequence diversity correlating with viral load set point (p = 0.07, r = 0.39). At 14 days post infection, 59.7% of Gag CTL epitopes contained non-consensus polymorphisms and over half of these (35.3%) comprised of previously described CTL escape variants. Consensus and variant CTL epitope proportions were equally distributed irrespective of the selecting host HLA allele and most epitopes remained unchanged over 12 months post infection. These data suggest that intrapatient diversity during acute infection is an indicator of disease outcome. In this setting, there is a high rate of transmitted CTL escape variants and limited immune selection in Gag during the first year of infection. These data have relevance for vaccine strategies designed to elicit effective CD8+ T cell immune responses.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4363590/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:14351098
Collections
- HMS Scholarly Articles [17917]
- SPH Scholarly Articles [6362]
Contact administrator regarding this item (to report mistakes or request changes)