A host-based whole genome sequencing study reveals novel risk loci associated with severity of influenza A(H1N1)pdm09 infection

Abstract

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 ( P < 1 × 10 −4 ) common SNVs enriched in PTBP3 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 FTSJ3 , CPVL , BST2 , NOD2 and MAVS . 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.

Causal relationship between blood traits and severe influenza A(H1N1)pdm09 infection in East Asian: A Mendelian randomization study

“…The statistical models were adjusted for covariates including age, sex, the top 10 principal components (PCs), and trait‐specific covariates. In a previous study, we outlined the specific workflow to construct the GWAS for the severity of H1N1pdm09 disease 12 . In brief, we collected samples from 165 patients infected with H1N1pdm09.…”

“…In this study, we employed a two‐sample MR analysis to investigate the causal relationship between human blood traits and the severity of H1N1pdm09 disease. We integrated our in‐house GWAS data on H1N1pdm09 disease severity 12 with the comprehensive GWAS summary of 44 blood traits from Biobank Japan (BBJ) 13 . This analysis allowed us to estimate the putative causal relationships between these traits and disease severity.…”

Identification of Causal Relationships between Gut Microbiota and Influenza a Virus Infection in Chinese by Mendelian Randomization

“…Real-time reverse transcription polymerase chain reaction (RT-PCR) was used for diagnosing H7N9 infection, following the Diagnostic and Treatment Protocol for Human Infection with Avian Influenza A (H7N9) (http://www.nhc.gov.cn/gjhzs/s7952/201304/34750c7e6 930463aac789b3e2156632f.shtml accessed on 30 May 2018). Similarly, summary statistics for H1N1 severity were collected from another preceding GWAS involving 165 Chinese H1N1pdm09 patients, confirmed by positive results of real-time RT-PCR [24]. Patients with mild symptoms (n = 95) were defined as outpatients not admitted to hospitals, while those with severe symptoms (n = 70) were hospitalized patients meeting specific criteria outlined in the Protocol for diagnosis and treatment of influenza (2019 version) [25].…”

HIF-1α promotes virus replication and cytokine storm in H1N1 virus-induced severe pneumonia through cellular metabolic reprogramming

“…Notably, multiple studies have shown that the expression of HIF-1α can also be upregulated under normoxic conditions ( Koyasu et al., 2018 ). A host-based whole-genome sequencing study identified the potential involvement of the HIF-1 transcription factor and the IFN-γ pathway in the pathogenesis of severe influenza A (H1N1) infection ( Li et al., 2021 ). H1N1 infection can cause lung and intestinal injury and imbalance of the intestinal flora.…”