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

Angela Nalwoga ORCID logo; Romin Roshan ORCID logo; Kyle Moore ORCID logo; Vickie Marshall; Wendell Miley; Nazzarena Labo; Marjorie Nakibuule; Stephen Cose ORCID logo; Rosemary Rochford; Robert Newton ORCID logo; +1 more... Denise Whitby ORCID logo; (2021) Kaposi's sarcoma-associated herpesvirus T cell responses in HIV seronegative individuals from rural Uganda. Nature communications, 12 (1). 7323-. ISSN 2041-1723 DOI: 10.1038/s41467-021-27623-8
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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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