Novel susceptibility loci for A(H7N9) infection identified by next generation sequencing and functional analysis

The A(H7N9) virus strain that emerged in 2013 was associated with a high fatality rate and may become a long-term threat to public health. A(H7N9) disease incidence is disproportionate to viral exposure, suggesting that host genetic factors may significantly influence susceptibility to A(H7N9) infec...

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Bibliographic Details
Published in:Scientific reports 2020-07, Vol.10 (1), p.11768-11768, Article 11768
Main Authors: Zhao, Baihui, Chen, Yongkun, Li, Mo, Zhou, Jianfang, Teng, Zheng, Chen, Jian, Zhao, Xue, Wu, Hao, Bai, Tian, Mao, Shenghua, Fang, Fanghao, Chu, Wei, Huang, Hailiang, Huai, Cong, Shen, Lu, Zhou, Wei, Sun, Liangdan, Zheng, Xiaodong, Cheng, Guangxia, Sun, Ye, Wang, Dayan, He, Lin, Shu, Yuelong, Zhang, Xi, Qin, Shengying
Format: Article
Language:English
Subjects:
Adult
Alleles
DQA1 protein
Etiology
Gene Frequency
Genetic factors
Genetic Loci
Genetic Predisposition to Disease
Genomes
Genotype
Genotype & phenotype
Genotypes
High-Throughput Nucleotide Sequencing
Histocompatibility antigen HLA
Host-Pathogen Interactions - genetics
Humans
Infections
Influenza A Virus, H7N9 Subtype
Influenza, Human - genetics
Influenza, Human - virology
Interferon
Male
Next-generation sequencing
Public health
Serum levels
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Summary:The A(H7N9) virus strain that emerged in 2013 was associated with a high fatality rate and may become a long-term threat to public health. A(H7N9) disease incidence is disproportionate to viral exposure, suggesting that host genetic factors may significantly influence susceptibility to A(H7N9) infection. Human genome variation in conferring risk for A(H7N9) infection in Chinese populations was identified by a two-stage investigation involving 121 A(H7N9) patients and 187 healthy controls using next generation sequencing followed by functional analysis. As a result, a low frequency variant (rs189256251; P = 0.0303, OR = 3.45, 95% CI 1.05-11.35, chi-square test) and three HLA alleles (DQB1*06:01, DQA1*05:05 and C*12:02) were identified in A(H7N9) infected volunteers. In an A549 cell line carrying the rs189256251 variant CT genotype, A(H7N9) infection incidence was elevated 6.665-fold over control cells carrying the CC genotype. Serum levels of interferon alpha were significantly lower in patients with the CT genotype compared to the CC genotype (P = 0.01). The study findings of genetic predisposition to A(H7N9) in the Chinese population may be valuable in systematic investigations of A(H7N9) disease etiology.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-68675-y