On [1?]. Among infected Caucasians, HLA-B*57 and HLA-B*27 are the best predictors
On [1?]. Among infected Caucasians, HLA-B*57 and HLA-B*27 are the best predictors of immune control [6, 7]. A better understanding of disease progression in subjects expressing protective HLA alleles such as these provides potentially valuable insights into the fundamental basis of HLA-mediated immune control, for which many distinct mechanisms have been proposed [8]. One mechanism believed to be*Correspondence: [email protected] 1 Department of Paediatrics, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, UK Full list of author information is available at the end of the articleimportant in contributing to the HLA associations with characteristic disease outcomes is the targeting of specific cytotoxic T lymphocyte (CTL) epitopes [9?7]. The subtype of HIV infection may therefore impact on disease control, by affecting the availability of certain specific T cell epitopes [18?0]. It remains unclear specifically which epitopes are most likely to induce the most effective anti-HIV immune responses. These considerations are important both for understanding the mechanisms of HLA-mediated immune control of viral replication and because CTL may play a critical role in HIV cure strategies [21]. Most studies of immune control in HIV-infected subjects expressing protective HLA alleles such as HLA-B*57:01 and B*27:05 have focused on Gag, and in particular the?2015 Brener et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, get AZD3759 provided you give appropriate credit to the original PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/25609842 author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Brener et al. Retrovirology (2015) 12:Page 2 ofdominant CD8+ T cell responses targeting epitopes within p24 Gag. We investigated the case of an HIV infected transmission pair in which the recipient expressed both HLA-B*27:05 and HLA-57:01. Despite expression of these protective HLA alleles, disease progression occurred over four years from aviremia (viral load <50 copies/ml plasma) to antiretroviral therapy (ART) initiation, following a decline in absolute CD4 count to <350 cells/mm3. This study pursues the hypothesis that the CD8+ T cell epitopes important for immune control are those in which escape is selected in association with, or prior to, disease progression. Conversely, if escape has not occurred in parallel with disease progression, this would imply responses that do not protect against progression. We ultra-deep sequenced fulllength HIV genomes using the Illumina MiSeq platform in both donor and recipient in order to define the mutations associated with disease progression.ResultsProgression in a UK transmission pair with CRF01_AE virus infectionWe studied an adult Caucasian transmission pair from the UK. The male donor (HLAA*02:01/32:B*13:02/14:01 C*06:02/08:02) is believed to have acquired HIV infection PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28914615 in Thailand, and subsequently to have infected the female recipient (HLA-A*02:01/02:01 B*27:05/57:01 C*01:02/06:02) in the UK. Both partners were diagnosed more than 2 years later when the recipient was HIV-tested during pregnancy (referred to as `time.
