title: Deep sequencing reveals the viral adaptation process of environment-derived H10N8 in mice.
abstract: The H10N8 virus was isolated from the water of Dongting Lake, China. Mice were infected while showing no obvious symptoms and replication was restricted to the lungs. When the wild-type virus was serially passaged in the lungs of mice, the resulting viruses became lethal and capable of replication in many other organs. This offered an applicable model for the exploration of viral genome gradual mutation during adaptation in mice. The different passage viruses from mice lung lavage were named P1, P3, P5, and P7, respectively. We sequenced the four viruses using next-generation sequencing (NGS) to analyze the dynamics of the H10N8 viral genome, polymorphism, and amino acid mutation of related proteins. We aimed to demonstrate how a mutant strain of low pathogenicity could become lethal to mice. Using Illumina high-throughput data, we detected the gradual mutations of F277S, C278Q, F611S and L653P in the polymerase acidic (PA) protein, and of L207V and E627K in the PB2 protein during adaptation. Interestingly, many amino acid sites mutated quickly; the others did so more slowly and remained in a heterozygous state for several generations. The PA amino acids S277 and Q278 have previously been found in clinical wild-type strains, including the human-H10N8 isolate in 2013. This demonstrates that the wild-type H10N8 virus had mutated to adapt to mammalian hosts. These data provide important reference information for influenza virus research.
authors.affiliation: CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Hubei 430071, China; Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, Hubei Key Laboratory of Industrial Biotechnology, College of Life Sciences, Hubei University, Hubei 430062, China; Center for Influenza Research and Early-warning (CASCIRE), Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Mei
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Hubei 430071, China; Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, Hubei Key Laboratory of Industrial Biotechnology, College of Life Sciences, Hubei University, Hubei 430062, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Chen
authors.affiliation: CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Hubei 430071, China; Center for Influenza Research and Early-warning (CASCIRE), Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Gao
authors.affiliation: CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Hubei 430071, China; Center for Influenza Research and Early-warning (CASCIRE), Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Zhao
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jin
authors.affiliation: Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, Hubei Key Laboratory of Industrial Biotechnology, College of Life Sciences, Hubei University, Hubei 430062, China. Electronic address: yxiaolan@163.com.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Yu
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China; Center for Influenza Research and Early-warning (CASCIRE), Chinese Academy of Sciences, Beijing 100101, China. Electronic address: chenqj@wh.iov.cn.
authors.forename: Quanjiao
authors.initials: Q
authors.lastname: Chen
mesh_terms: D000220:Adaptation, Biological; D000818:Animals; D002681:China; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D065926:Influenza A Virus, H10N8 Subtype / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000821:virology*; D051379:Mice; D009154:Mutation; D059645:Mutation Rate; D009976:Orthomyxoviridae Infections / Q000821:virology; D012367:RNA, Viral / Q000032:analysis; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics; D017423:Sequence Analysis, RNA / Q000379:methods*; D014764:Viral Proteins / Q000235:genetics; D014779:Virus Replication; D014871:Water Microbiology
chemical_list: C061290:PA protein, influenza viruses; C057027:PB2 protein, Influenzavirus A; D012367:RNA, Viral; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase
keywords: H10N8 virus; Mouse lung adaption; Next-generation sequencing (NGS)