Incoming HIV virion-derived Gag Spacer Peptide 2 (p1) is a target of effective CD8+ T cell antiviral responses.

Cell reports 2021 May 11

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Persistence of HIV through integration into host DNA in CD4+ T cells presents a major barrier to virus eradication. Viral integration may be curtailed when CD8+ T cells are triggered to kill infected CD4+ T cells through recognition of histocompatibility leukocyte antigen (HLA) class I-bound peptides derived from incoming virions. However, this has been reported only in individuals with "beneficial" HLA alleles that are associated with superior HIV control. Through interrogation of the pre-integration immunopeptidome, we obtain proof of early presentation of a virion-derived HLA-A∗02:01-restricted epitope, FLGKIWPSH (FH9), located in Gag Spacer Peptide 2 (SP2). FH9-specific CD8+ T cell responses are detectable in individuals with primary HIV infection and eliminate HIV-infected CD4+ T cells prior to virus production in vitro. Our data show that non-beneficial HLA class I alleles can elicit an effective antiviral response through early presentation of HIV virion-derived epitopes and also demonstrate the importance of SP2 as an immune target. Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Hongbing Yang, Anuska Llano, Samandhy Cedeño, Annette von Delft, Angelica Corcuera, Geraldine M Gillespie, Andrew Knox, Darren B Leneghan, John Frater, Wolfgang Stöhr, Sarah Fidler, Beatriz Mothe, Johnson Mak, Christian Brander, Nicola Ternette, Lucy Dorrell, Research in Viral Eradication of Reservoirs (RIVER) trial study group. Incoming HIV virion-derived Gag Spacer Peptide 2 (p1) is a target of effective CD8+ T cell antiviral responses. Cell reports. 2021 May 11;35(6):109103