HIV-1 adaptation to antigen processing results in population-level immune evasion and affects subtype diversification. Cell Reports, 7: doi: 10.1016/j.celrep.2014.03.031 (2014).

Publication Latest Publications

Title: HIV-1 adaptation to antigen processing results in population-level immune evasion and affects subtype diversification
Authors: Tenzer S, Crawford H, Pymm P, Gifford R, Sreenu VB, Weimershaus M, de Oliveira T, Burgevin A, Gerstoft J, Akkad N, Lunn D, Fugger L, Bell J, Schild H, van Endert P, Iversen AK..
Journal: Cell Reports,7:doi: 10.1016/j.celrep.2014.03.031 (2014)

Journal Impact Factor (I.F.): 10.5
Number of citations (Google Scholar): 5

Abstract

The recent HIV-1 vaccine failures highlight the need to better understand virus-host interactions. One key question is why CD8(+) T cell responses to two HIV-Gag regions are uniquely associated with delayed disease progression only in patients expressing a few rare HLA class I variants when these regions encode epitopes presented by ~30 more common HLA variants.

By combining epitope processing and computational analyses of the two HIV subtypes responsible for ~60% of worldwide infections, we identified a hitherto unrecognized adaptation to the antigen-processing machinery through substitutions at subtype-specific motifs. Multiple HLA variants presenting epitopes situated next to a given subtype-specific motif drive selection at this subtype-specific position, and epitope abundances correlate inversely with the HLA frequency distribution in affected populations.

This adaptation reflects the sum of intrapatient adaptations, is predictable, facilitates viral subtype diversification, and increases global HIV diversity. Because low epitope abundance is associated with infrequent and weak T cell responses, this most likely results in both population-level immune evasion and inadequate responses in most people vaccinated with natural HIV-1 sequence constructs. Our results suggest that artificial sequence modifications at subtype-specific positions in vitro could refocus and reverse the poor immunogenicity of HIV proteins.

Download: Full text paper

Citation: Tenzer S, Crawford H, Pymm P, Gifford R, Sreenu VB, Weimershaus M, de Oliveira T, Burgevin A, Gerstoft J, Akkad N, Lunn D, Fugger L, Bell J, Schild H, van Endert P, Iversen AK.. HIV-1 adaptation to antigen processing results in population-level immune evasion and affects subtype diversification Cell Reports,7:doi: 10.1016/j.celrep.2014.03.031 (2014).


Impact of point-of-care Xpert MTB/RIF on tuberculosis treatment initiation: a cluster randomised trial
Journal: Am J Respir Crit Care Med (2017)

Hyperbilirubinemia in atazanavir-treated human immunodeficiency virus-infected patients: the impact of the UGT1A1*28 allele
Journal: Pharmacogenomics and Personalized Medicine (2017)

Rates of virological suppression and drug resistance in adult HIV-1-positive patients attending primary healthcare facilities in KwaZulu-Natal, South Africa
Journal: Journal of Antimicrobial Chemotherapy (2017)
All publications...


KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), K-RITH Tower Building, Nelson R Mandela School of Medicine, UKZN

Contact: Prof. Tulio de Oliveira, Tel: +27 31 260 4898, Email: tuliodna@gmail.com & deoliveira@ukzn.ac.za

Page design updated 2013. Many of the pages were previously hosted at bioafrica.net.