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. 2021 Dec 16;12(1):7323.
doi: 10.1038/s41467-021-27623-8.

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

Angela Nalwoga  1   2 , Romin Roshan  3 , Kyle Moore  3 , Vickie Marshall  3 , Wendell Miley  3 , Nazzarena Labo  3 , Marjorie Nakibuule  4 , Stephen Cose  4   5 , Rosemary Rochford  6 , Robert Newton  7 , Denise Whitby  8
Affiliations

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

Angela Nalwoga et al. Nat Commun. .

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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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. KSHV-specific IFN-γ responses of 40 Ugandans aged 6–87 years.
Ex vivo ELISpot assay was used to determine IFN-γ responses to KSHV overlapping peptide pools. Spot forming cells (SFC) per million PBMCs were recorded for each reaction. The intensity of the purple colour correlates with the number of SFC per million PBMCs. The raw data used to draw this graph are shown in Supplementary Data 2. SIV Simian immunodeficiency virus, CEF CMV + EBV + flu cocktail, EBV Epstein–Barr virus. Heatmap drawn in GraphPad Prism version 8.0.1. Source data are provided as a Source Data file.
Fig. 2
Fig. 2. KSHV-specific IFN-γ responses of 76 Ugandans aged 18–50 years.
Ex vivo ELISpot assay was used to determine IFN-γ responses to KSHV overlapping peptide pools. Spot forming cells (SFCs) per million PBMCs were recorded for each reaction. The intensity of the purple colour correlates with the number of SFCs per million PBMCs. The raw data used to draw this graph are shown in Supplementary Data 1. SIV Simian immunodeficiency virus, EBV Epstein–Barr virus, CEF CMV + EBV + flu cocktail. Heatmap drawn in GraphPad Prism version 8.0.1. Source data are provided as a Source Data file.
Fig. 3
Fig. 3. Proportion of individuals with IFN-γ responses to various KSHV ORFs and controls peptide pools.
Dots represent the percentage of individuals reacting to the different KSHV antigens. Error bars represent 95% confidence intervals. N = 116 study participants. SIV Simian immunodeficiency virus, EBV Epstein–Barr virus, CEF CMV + EBV + flu cocktail. Graph drawn in GraphPad Prism version 8.0.1. Source data are provided as a Source Data file.
Fig. 4
Fig. 4. Proportion of individuals responding to atleast one KSHV ORF.
. Individuals categorized by age group (a) and sex (b).
Fig. 5
Fig. 5. Immune responses (IFN-y) and IgG antibody) to K8.1 and ORF73 as well as IFN-y responses to EBV and CMV+EBV+flu cocktail-CEF in individuals with and without KSHV DNA in peripheral blood mononuclear cells (PBMC).
a, g IFN-y responses to K8.1; b IgG antibody responses to K8.1; c IgG antibody responses to ORF73; d, h IFN-y responses to ORF73; e IFN-y responses to EBV; f IFN-y responses to CEF.
Fig. 6
Fig. 6. KSHV DNA levels in peripheral blood mononuclear cells (PBMC) by number of reactive peptide pools.
(a) individuals grouped in 3 categories; (b) individuals grouped in 5 categories.
See this image and copyright information in PMC

References

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