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

Kaposi's sarcoma-associated herpesvirus T cell responses in HIV seronegative individuals from rural Uganda.
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乌干达农村地区HIV血清阴性患者的卡波西肉瘤相关疱疹病毒T细胞反应。

DOI:
10.1038/s41467-021-27623-8
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发表时间:
2021-12-16
影响因子:
16.6
通讯作者:
Whitby D
Whitby D
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Nalwoga A;Roshan R;Moore K;Marshall V;Miley W;Labo N;Nakibuule M;Cose S;Rochford R;Newton R;Whitby D

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T 细胞对卡波西肉瘤相关疱疹病毒 (KSHV) 的反应可能对于控制 KSHV 感染和预防相关疾病至关重要,但目前尚不清楚。乌干达农村地区的 KSHV 患病率高达 90% 以上。在这里,我们研究了来自乌干达农村人口的 HIV 阴性个体中 IFN-γ T 细胞对 KSHV 蛋白质组的反应。我们使用离体 IFN-γ ELISpot 测定法,对 116 名个体的外周血单核细胞 (PBMC) 进行跨越 83 个 KSHV 开放阅读框 (ORF) 的重叠肽池分析。 KSHV 特异性 T 细胞 IFN-γ 反应强度低且异质,没有免疫优势的证据;相比之下,IFN-γ对 Epstein-Barr 病毒、巨细胞病毒和流感肽的反应频繁且强烈。与没有 KSHV DNA 的个体相比,PBMC 中带有 KSHV DNA 的个体对 ORF73 的 IFN-γ 反应较高 (p = 0.02),对 K8.1 的反应较低 (p = 0.004)。总之,我们证明了免疫能力强的个体对 KSHV 的低强度、异质性 T 细胞反应。 T 细胞对卡波西肉瘤相关疱疹病毒的反应对于控制感染和免疫病理学至关重要,但在免疫功能正常的患者中研究很少。在这里,作者描述了乌干达农村免疫功能正常患者中 T 细胞对卡波西肉瘤相关疱疹病毒蛋白质组的反应。
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. 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.
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