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

Angela Nalwoga (), Romin Roshan, Kyle Moore, Vickie Marshall, Wendell Miley, Nazzarena Labo, Marjorie Nakibuule, Stephen Cose, Rosemary Rochford, Robert Newton and Denise Whitby ()
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Angela Nalwoga: MRC/UVRI and LSHTM Uganda Research Unit
Romin Roshan: Frederick National Laboratory for Cancer Research
Kyle Moore: Frederick National Laboratory for Cancer Research
Vickie Marshall: Frederick National Laboratory for Cancer Research
Wendell Miley: Frederick National Laboratory for Cancer Research
Nazzarena Labo: Frederick National Laboratory for Cancer Research
Marjorie Nakibuule: MRC/UVRI and LSHTM Uganda Research Unit
Stephen Cose: MRC/UVRI and LSHTM Uganda Research Unit
Rosemary Rochford: University of Colorado, Anschutz Medical Campus
Robert Newton: University of York
Denise Whitby: Frederick National Laboratory for Cancer Research

Nature Communications, 2021, vol. 12, issue 1, 1-9

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-27623-8

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