title: Dynamic changes in host gene expression associated with H5N8 avian influenza virus infection in mice.
abstract: Emerging outbreaks of newly found, highly pathogenic avian influenza (HPAI) A(H5N8) viruses have been reported globally. Previous studies have indicated that H5N8 pathogenicity in mice is relatively moderate compared with H5N1 pathogenicity. However, detailed mechanisms underlying avian influenza pathogenicity are still undetermined. We used a high-throughput RNA-seq method to analyse host and pathogen transcriptomes in the lungs of mice infected with A/MD/Korea/W452/2014 (H5N8) and A/EM/Korea/W149/2006 (H5N1) viruses. Sequenced numbers of viral transcripts and expression levels of host immune-related genes at 1 day post infection (dpi) were higher in H5N8-infected than H5N1-infected mice. Dual sequencing of viral transcripts revealed that in contrast to the observations at 1 dpi, higher number of H5N1 genes than H5N8 genes was sequenced at 3 and 7 dpi, which is consistent with higher viral titres and virulence observed in infected lungs in vivo. Ingenuity pathway analysis revealed a more significant upregulation of death receptor signalling, driven by H5N1 than with H5N8 infection at 3 and 7 dpi. Early induction of immune response-related genes may elicit protection in H5N8-infected mice, which correlates with moderate pathogenicity in vivo. Collectively, our data provide new insight into the underlying mechanisms of the differential pathogenicity of avian influenza viruses.
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Tropical Medicine, Medical Microbiology and Pharmacology, Pacific Center for Emerging Infectious Diseases Research, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, 96822, USA.
authors.forename: Mukesh
authors.initials: M
authors.lastname: Kumar
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Hyeok-il
authors.initials: HI
authors.lastname: Kwon
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Korea University Guro Hospital, Seoul, 152-703, Republic of Korea.
authors.forename: Rak-Kyun
authors.initials: RK
authors.lastname: Seong
authors.affiliation: Department of Nanobiomedical Science, Dankook University, Cheonan, 330-714 Republic of Korea.
authors.forename: Kyudong
authors.initials: K
authors.lastname: Han
authors.affiliation: Department of Global Medical Science, Sungshin Women's University, Seoul, 136-742 Republic of Korea.
authors.forename: Jae-min
authors.initials: JM
authors.lastname: Song
authors.affiliation: College of Veterinary Medicine, Chungnam National University, Daejeon, 305-764 Republic of Korea.
authors.forename: Chul-Joong
authors.initials: CJ
authors.lastname: Kim
authors.affiliation: College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Young-Ki
authors.initials: YK
authors.lastname: Choi
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Korea University Guro Hospital, Seoul, 152-703, Republic of Korea.|Department of Microbiology, College of Medicine, Korea University, Seoul, 136-701 Republic of Korea.
authors.forename: Ok Sarah
authors.initials: OS
authors.lastname: Shin
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015967:Gene Expression Regulation, Viral; D059014:High-Throughput Nucleotide Sequencing; D054884:Host-Pathogen Interactions / Q000235:genetics*; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics; D009980:Influenza A virus / Q000145:classification / Q000235:genetics; D007372:Interferons / Q000378:metabolism; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D053218:Receptors, Death Domain / Q000378:metabolism; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D053218:Receptors, Death Domain; D007372:Interferons