Kaposi's sarcoma-associated herpesvirus T cell responses in HIV seronegative individuals from rural Uganda

Abstract

T cell responses to Kaposi's sarcoma-associated herpesvirus (KSHV) are likely essential in the control of KSHV infection and protection from associated disease, but remain poorly characterised. KSHV prevalence in rural Uganda is high at >90%. Here we investigate IFN- γ T cell responses to the KSHV proteome in HIV-negative individuals from a rural Ugandan population. We use an ex-vivo IFN- γ ELISpot assay with overlapping peptide pools spanning 83 KSHV open reading frames (ORF) on peripheral blood mononuclear cells (PBMC) from 116 individuals. KSHV-specific T cell IFN- γ responses are of low intensity and heterogeneous, with no evidence of immune dominance; by contrast, IFN- γ responses to Epstein-Barr virus, Cytomegalovirus and influenza peptides are frequent and intense. Individuals with KSHV DNA in PBMC have higher IFN- γ responses to ORF73 (p = 0.02) and lower responses to K8.1 (p = 0.004) when compared with those without KSHV DNA. In summary, we demonstrate low intensity, heterogeneous T cell responses to KSHV in immune-competent individuals.

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Item Type:	Article
Authors/Creators:	Nalwoga, Angela Roshan, Romin Moore, Kyle Marshall, Vickie Miley, Wendell Labo, Nazzarena Nakibuule, Marjorie Cose, Stephen Rochford, Rosemary Newton, Robert https://orcid.org/0000-0001-6715-9153 Whitby, Denise
Copyright, Publisher and Additional Information:	© 2021. The Author(s). Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.
Dates:	Accepted: 2 December 2021 Published: 16 December 2021
Institution:	The University of York
Academic Units:	The University of York > Faculty of Sciences (York) > Health Sciences (York)
Depositing User:	Pure (York)
Date Deposited:	21 Dec 2021 16:20
Last Modified:	11 Apr 2025 23:27
Published Version:	https://doi.org/10.1038/s41467-021-27623-8
Status:	Published
Refereed:	Yes
Identification Number:	10.1038/s41467-021-27623-8
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:181863

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Kaposi's sarcoma-associated herpesvirus T cell responses in HIV seronegative individuals from rural Uganda

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