研究人员对拥有欧洲和非洲血统的男性进行测试,采用单细胞RNA测序的方法来量化他们的外周血单核细胞对感染流感后的反应差异。他们发现遗传祖先效应是常见的,但具有高度的细胞类型特异性。较高的欧洲血统水平与早期感染中 I型干扰素途径活性的增加有关,这将能预测在之后的时间点病毒滴度会降低。大量群体相关的变异可以通过由遗传祖先来区分的Cis-表达数量性状基因座来解释。
此外,在与COVID-19疾病严重程度相关的基因中,富集了很多遗传祖先相关基因,提示早期免疫应答促成了多种病毒感染应答反应的遗传祖先相关差异。
据悉,人类对传染性疾病的易感性不同,部分原因是人类感染疾病后产生的免疫应答反应的不同。
附:英文原文
Title: Genetic ancestry effects on the response to viral infection are pervasive but cell type specific
Author: Haley E. Randolph, Jessica K. Fiege, Beth K. Thielen, Clayton K. Mickelson, Mari Shiratori, Joo Barroso-Batista, Ryan A. Langlois, Luis B. Barreiro
Issue&Volume: 2021-11-26
Abstract: Humans differ in their susceptibility to infectious disease, partly owing to variation in the immune response after infection. We used single-cell RNA sequencing to quantify variation in the response to influenza infection in peripheral blood mononuclear cells from European- and African-ancestry males. Genetic ancestry effects are common but highly cell type specific. Higher levels of European ancestry are associated with increased type I interferon pathway activity in early infection, which predicts reduced viral titers at later time points. Substantial population-associated variation is explained by cis-expression quantitative trait loci that are differentiated by genetic ancestry. Furthermore, genetic ancestry–associated genes are enriched among genes correlated with COVID-19 disease severity, suggesting that the early immune response contributes to ancestry-associated differences for multiple viral infection outcomes.
DOI: abg0928
Source: https://www.science.org/doi/10.1126/science.abg0928