Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-27623-8
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Funding
- Frederick National Laboratory for Cancer Research [HHSN261200800001E]
- NCI [75N91019D00024]
- Department of Immunology and Microbiology University of Colorado Anschutz medical campus, NIH [1 RO1 CA239588-01]
- African Partnership for Chronic Disease Research (APCDR), University of Cambridge, United Kingdom
- Makerere University-Uganda Virus Research Institute Centre of Excellence for Infection and Immunity Research and Training (MUII)
- DELTAS Africa Initiative [107743]
- African Academy of Sciences (AAS)
- Alliance for Accelerating Excellence in Science in Africa (AESA)
- New Partnership for Africa's Development Planning and Coordinating Agency (NEPAD Agency)
- Wellcome Trust [107743]
- UK Government
- UK Medical Research Council (MRC)
- UK Department for International Development (DFID)
- European Union
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The T cell responses to KSHV in immunocompetent individuals in rural Uganda are of low intensity and heterogeneous, suggesting a complex immune response to the virus in this population.
The T cell response to Kaposi sarcoma-associated herpesvirus is critical to controlling infection and immunopathology but has been poorly explored in immunocompetent patients. Here the authors characterise the T cell response to the Kaposi sarcoma-associated herpesvirus proteome in immunocompetent patients from rural Uganda. 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- gamma T cell responses to the KSHV proteome in HIV-negative individuals from a rural Ugandan population. We use an ex-vivo IFN- gamma 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- gamma responses are of low intensity and heterogeneous, with no evidence of immune dominance; by contrast, IFN- gamma responses to Epstein-Barr virus, Cytomegalovirus and influenza peptides are frequent and intense. Individuals with KSHV DNA in PBMC have higher IFN- gamma 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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