Human Leukocyte Antigen Susceptibility Map for Severe Acute Respiratory Syndrome Coronavirus 2
Human Leukocyte Antigen Susceptibility Map for Severe Acute Respiratory Syndrome Coronavirus 2
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DOI：
10.1128/jvi.00510-20
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发表时间：
2020-07-01
影响因子：
5.4
通讯作者：
Thompson, Reid F.
中科院分区：
文献类型：
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作者：
Nguyen, Austin;David, Julianne K.;Thompson, Reid F.
三个主要组织相容性复合体（MHC） I类基因（人类白细胞抗原A [HLA-A]、-B和-C基因）的遗传变异可能影响对严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）引起的疾病的易感性和严重程度，SARS-CoV-2是2019年冠状病毒病（COVID-19）的罪魁罪魁。我们对所有SARS-CoV-2肽在145个HLA-A、-B和-C基因型上的病毒肽- mhc I类结合亲和力进行了全面的计算机分析。我们进一步探索了先前接触四种常见人类冠状病毒所产生的交叉保护性免疫的可能性。SARS-CoV-2蛋白质组成功采样，并由HLA等位基因多样性代表。然而，我们发现HLA-B*46:01对SARS- cov -2的预测结合肽最少，这表明携带该等位基因的个体可能特别容易感染COVID-19，就像之前证明的那样（M. Lin, h . t . Tseng， J. A. Trejaut, h . l . l .）。Lee等，BMC医学杂志，2003,4:9,https://bmcmedgenet.biomedcentral.com/articles/10.1186/1471-2350-4-9)。相反，我们发现HLAB*15:03表现出最大的能力呈递高度保守的SARS-CoV-2肽，这些肽在常见的人类冠状病毒中是共享的，这表明它可以实现基于交叉保护性t细胞的免疫。最后，我们报告了在当前大流行背景下具有潜在流行病学影响的HLA类型的全球分布。重要性：个体遗传变异可能有助于解释不同人群对病毒的不同免疫反应。特别是，了解HLA的变化如何影响COVID-19的进程可以帮助识别患有该疾病的高风险个体。HLA分型可以快速且廉价。在可行的情况下，将HLA分型与COVID-19检测配对可以改善对人群中病毒性疾病严重程度的评估。随着针对SARS-CoV-2（导致COVID-19的病毒）的疫苗的开发，HLA高危型的个体可能会优先接种疫苗。
Genetic variability across the three major histocompatibility complex (MHC) class I genes (human leukocyte antigen A [HLA-A], -B, and -C genes) may affect susceptibility to and severity of the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). We performed a comprehensive in silico analysis of viral peptide-MHC class I binding affinity across 145 HLA-A, -B, and -C genotypes for all SARS-CoV-2 peptides. We further explored the potential for cross-protective immunity conferred by prior exposure to four common human coronaviruses. The SARS-CoV-2 proteome was successfully sampled and was represented by a diversity of HLA alleles. However, we found that HLA-B*46:01 had the fewest predicted binding peptides for SARS-CoV-2, suggesting that individuals with this allele may be particularly vulnerable to COVID-19, as they were previously shown to be for SARS (M. Lin, H.-T. Tseng, J. A. Trejaut, H.-L. Lee, et al., BMC Med Genet 4:9, 2003, https://bmcmedgenet.biomedcentral.com/articles/10.1186/1471-2350-4-9). Conversely, we found that HLAB*15:03 showed the greatest capacity to present highly conserved SARS-CoV-2 peptides that are shared among common human coronaviruses, suggesting that it could enable cross-protective T-cell-based immunity. Finally, we reported global distributions of HLA types with potential epidemiological ramifications in the setting of the current pandemic.IMPORTANCE Individual genetic variation may help to explain different immune responses to a virus across a population. In particular, understanding how variation in HLA may affect the course of COVID-19 could help identify individuals at higher risk from the disease. HLA typing can be fast and inexpensive. Pairing HLA typing with COVID-19 testing where feasible could improve assessment of severity of viral disease in the population. Following the development of a vaccine against SARS-CoV-2, the virus that causes COVID-19, individuals with high-risk HLA types could be prioritized for vaccination.