MHC class II genes mediate susceptibility and resistance to coronavirus infections in bats

Understanding the immunogenetic basis of coronavirus (CoV) susceptibility in major pathogen reservoirs, such as bats, is central to infer their zoonotic potential. Members of the cryptic Hipposideros bat species complex differ in CoV susceptibility, but the underlying mechanisms remain unclear. The genes of the major histocompatibility complex (MHC) are the best understood genetic basis of pathogen resistance, and differences in MHC diversity are one possible reason for asymmetrical infection patterns among closely related species. Here, we aimed to link asymmetries in observed CoV (CoV-229E, CoV-2B, and CoV-2Bbasal) susceptibility to immunogenetic differences amongst four Hipposideros bat species. From the 2,072 bats assigned to their respective species using the mtDNA cytochrome b gene, members of the most numerous and ubiquitous species, Hipposideros caffer D, were most infected with CoV-229E and SARS-related CoV-2B. Using a subset of 569 bats we determined that much of the existent ..., Bats were live-trapped at five locations with one to three roosting sites in 12 two-month-long capture periods between September 2010 and August 2012 in Central Ghana, West Africa (Figure 1A). If possible, all bats were classified to species level using morphological characteristics. Morphometric details such as forearm length or weight were described elsewhere (Baldwin et al., 2021). Two minimally invasive wing punches (3mm) were taken from each bat and stored in molecular-grade ethanol at -20°C for DNA extraction. Additionally, faecal samples were collected and stored in RNAlater at -80°C for virus and microbiome screening.
DNA extraction was performed using wing punch tissue from 2,072 bats of the 6,654 bats assigned to the H. caffer complex or H. abae. The extraction followed an ammonium acetate protocol (Nicholls et al., 2000). Building on previous primer designs for the Hipposideros species complex (Vallo et al., 2008), the mtDNA cytochrome b gene (cytb) was amplified by polymeras..., We provide three datasets (Hip_MHC-CoV-data_Schmidetal2023MolEcol.csv; Hip_community-data_Schmidetal2023MolEcol.csv; and Hip_community-CoV-data_Schmidetal2023MolEcol.csv) as CSV format. They form the backbone of the analysis performed in the associated R Markdown (Schmid.Meyer_MolEcol23_Rscript.Rmd).
All statistical data analyses were computed in the open-access platform R. 
Additionally, we provide an Excel file (Hip_MHCII-DRB2_sequences_Schmidetal2023MolEcol) with four sheets listing the MHC class II DRB exon 2 allele sequences identified among the four hipposiderid species.

解析蝙蝠等主要病原体储存宿主对冠状病毒（coronavirus, CoV）的易感性免疫遗传学基础，对于推断其人畜共患病传播潜力至关重要。隐存蹄蝠属（Hipposideros）物种复合体的类群对CoV的易感性存在差异，但其潜在机制仍不明晰。主要组织相容性复合体（major histocompatibility complex, MHC）基因是目前研究最为透彻的病原体抗性遗传基础，而MHC多样性差异是近缘物种间感染模式不对称的潜在原因之一。
本研究旨在将观测到的四种蹄蝠属蝙蝠对CoV（CoV-229E、CoV-2B及CoV-2Bbasal）的易感性不对称性，与四种蹄蝠的免疫遗传学差异关联起来。通过线粒体DNA细胞色素b（mtDNA cytochrome b）基因将2072只蝙蝠鉴定到对应物种后，研究发现数量最多、分布最广的南非蹄蝠D类群（Hipposideros caffer D）感染CoV-229E和SARS相关冠状病毒2B的比例最高。
通过对569只蝙蝠的亚群分析，我们发现现存的大部分…… 研究于2010年9月至2012年8月间，在西非加纳中部的5个点位（每个点位设1-3个栖息位点）开展了12次为期2个月的捕获工作，期间活体捕捉蝙蝠。若条件允许，所有蝙蝠均通过形态学特征鉴定到物种水平。蝙蝠的形态测量参数（如前臂长、体重等）细节已在其他研究中发表（Baldwin et al., 2021）。
每只蝙蝠采集3mm的微创翼膜活检组织，保存于-20℃的分子级乙醇中用于DNA提取。此外，收集粪便样本并置于-80℃的RNAlater组织保存试剂中保存，用于病毒和微生物组筛选。
针对6654只被鉴定为南非蹄蝠复合体或阿巴蹄蝠（H. abae）的蝙蝠，我们从其中2072只的翼膜活检组织中提取DNA，提取流程遵循乙酸铵法（Nicholls et al., 2000）。本研究基于此前针对蹄蝠属物种复合体的引物设计方案（Vallo et al., 2008），通过聚合酶……扩增线粒体DNA细胞色素b基因（cytb）……
本研究提供三份逗号分隔值（CSV）格式数据集：Hip_MHC-CoV-data_Schmidetal2023MolEcol.csv、Hip_community-data_Schmidetal2023MolEcol.csv以及Hip_community-CoV-data_Schmidetal2023MolEcol.csv，这些数据集是关联R Markdown脚本（Schmid.Meyer_MolEcol23_Rscript.Rmd）中分析工作的核心支撑数据。
所有统计数据分析均在开源统计平台R中完成。
此外，本研究还提供一份Excel文件（Hip_MHCII-DRB2_sequences_Schmidetal2023MolEcol），其包含四个工作表，分别列出了四种蹄蝠科蝙蝠中鉴定到的主要组织相容性复合体II类DRB基因外显子2等位基因序列。