Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, People's Republic of China.
Emerg Microbes Infect. 2021 Dec;10(1):123-131. doi: 10.1080/22221751.2020.1870412.
Influenza A(H1N1)pdm09 virus has remained in a seasonal circulation since being recognized in 2009. Although it followed a mild course in most patients, in others it caused a series of severe clinical illnesses. Epidemiologic studies have implicated that host factors have a major influence on the disease severity of influenza A(H1N1)pdm09 infection. However, an understanding of relevant genetic variations and the underlying mechanisms is still limited. In this present study, we used a host-based whole genome sequencing (WGS) method to comprehensively explore the genetic risk loci associated with severity of influenza A(H1N1)pdm09 infection. From the common single-nucleotide variants (SNVs) analysis, we identified the abnormal nominally significant ( < 1 × 10) common SNVs enriched in gene. The results of rare functional SNVs analysis supported that there were several novel candidate genes might confer risk of severe influenza A(H1N1)pdm09 diseases, such as , , , and . Moreover, our results of gene set based analysis indicated that the HIF-1 transcription factor and IFN-γ pathway might play an important role in the underlying mechanism of severe influenza A(H1N1)pdm09. These findings will increase our knowledge about biological mechanism underlying the severe influenza A(H1N1)pdm09 and facilitate to design novel personalized treatments.
自 2009 年被发现以来，甲型 H1N1 流感病毒一直在季节性流行。虽然它在大多数患者中表现为轻度病程，但在其他患者中，它会引起一系列严重的临床疾病。流行病学研究表明，宿主因素对甲型 H1N1 流感的疾病严重程度有重大影响。然而，对于相关遗传变异和潜在机制的理解仍然有限。在本研究中，我们使用基于宿主的全基因组测序（WGS）方法全面探索与甲型 H1N1 流感感染严重程度相关的遗传风险位点。从常见的单核苷酸变异（SNV）分析中，我们确定了在基因中富集的异常名义显著（<1×10）常见 SNV。罕见功能 SNV 分析的结果支持存在几个可能导致严重甲型 H1N1 流感风险的新候选基因，例如、、、和。此外，我们基于基因集的分析结果表明，HIF-1 转录因子和 IFN-γ 途径可能在严重甲型 H1N1 流感的潜在机制中发挥重要作用。这些发现将增加我们对严重甲型 H1N1 流感的潜在生物学机制的认识，并有助于设计新的个性化治疗方法。
