title: Sequencing, annotation, and characterization of the influenza ferret infectome.
abstract: Ferrets have become an indispensable tool in the understanding of influenza virus virulence and pathogenesis. Furthermore, ferrets are the preferred preclinical model for influenza vaccine and therapeutic testing. Here we characterized the influenza infectome during the different stages of the infectious process in ferrets with and without prior specific immunity to influenza. RNA from lung tissue and lymph nodes from infected and naïve animals was subjected to next-generation sequencing, followed by de novo data assembly and annotation of the resulting sequences; this process generated a library comprising 13,202 ferret mRNAs. Gene expression profiles during pandemic H1N1 (pdmH1N1) influenza virus infection were analyzed by digital gene expression and solid support microarrays. As expected during primary infection, innate immune responses were triggered in the lung tissue; meanwhile, in the lymphoid tissue, genes encoding antigen presentation and maturation of effector cells of adaptive immunity increased dramatically. After 5 days postinfection, the innate immune gene expression was replaced by the adaptive immune response, which correlates with viral clearance. Reinfection with homologous pandemic influenza virus resulted in a diminished innate immune response, early adaptive immune gene regulation, and a reduction in clinical severity. The fully annotated ferret infectome will be a critical aid to the understanding of the molecular events that regulate disease severity and host-influenza virus interactions among seasonal, pandemic, and highly pathogenic avian influenzas.
authors.affiliation: Division of Immunology, International Institute of Infection and Immunity, Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: León
authors.forename: David
authors.initials: D
authors.lastname: Banner
authors.forename: Luoling
authors.initials: L
authors.lastname: Xu
authors.forename: Longsi
authors.initials: L
authors.lastname: Ran
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Peng
authors.forename: Kang
authors.initials: K
authors.lastname: Yi
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.forename: Fengping
authors.initials: F
authors.lastname: Xu
authors.forename: Jinrong
authors.initials: J
authors.lastname: Huang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhao
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lin
authors.forename: Stephen H S
authors.initials: SH
authors.lastname: Huang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Fang
authors.forename: Alyson A
authors.initials: AA
authors.lastname: Kelvin
authors.forename: Ted M
authors.initials: TM
authors.lastname: Ross
authors.forename: Amber
authors.initials: A
authors.lastname: Farooqui
authors.forename: David J
authors.initials: DJ
authors.lastname: Kelvin
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005289:Ferrets; D054884:Host-Pathogen Interactions; D053118:Influenza A Virus, H1N1 Subtype / Q000472:pathogenicity*; D008168:Lung / Q000473:pathology / Q000821:virology; D008198:Lymph Nodes / Q000473:pathology / Q000821:virology; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000473:pathology*; D017422:Sequence Analysis, DNA; D013997:Time Factors; D059467:Transcriptome