title: Human H7N9 and H5N1 influenza viruses differ in induction of cytokines and tissue tropism.
abstract: Since emerging in 2013, the avian-origin H7N9 influenza viruses have resulted in over 400 human infections, leading to 115 deaths to date. Although the epidemiology differs from human highly pathogenic avian H5N1 influenza virus infections, there is a similar rapid progression to acute respiratory distress syndrome. The aim of these studies was to compare the pathological and immunological characteristics of a panel of human H7N9 and H5N1 viruses in vitro and in vivo. Although there were similarities between particular H5N1 and H7N9 viruses, including association between lethal disease and spread to the alveolar spaces and kidney, there were also strain-specific differences. Both H5N1 and H7N9 viruses are capable of causing lethal infections, with mortality correlating most strongly with wider distribution of viral antigen in the lungs, rather than with traditional measures of virus titer and host responses. Strain-specific differences included hypercytokinemia in H5N1 infections that was not seen with the H7N9 infections regardless of lethality. Conversely, H7N9 viruses showed a greater tropism for respiratory epithelium covering nasal passages and nasopharynx-associated lymphoid tissue than H5N1 viruses, which may explain the enhanced transmission in ferret models. Overall, these studies highlight some distinctive properties of H5N1 and H7N9 viruses in different in vitro and in vivo models.
  
  
  OBJECTIVE
  The novel avian-origin H7N9 pandemic represents a serious threat to public health. The ability of H7N9 to cause serious lung pathology, leading in some cases to the development of acute respiratory distress syndrome, is of particular concern. Initial reports of H7N9 infection compared them to infections caused by highly pathogenic avian (HPAI) H5N1 viruses. Thus, it is of critical importance to understand the pathology and immunological response to infection with H7N9 compared to HPAI H5N1 viruses. We compared these responses in both in vitro and in vivo models, and found that H5N1 and H7N9 infections exhibit distinct pathological, immunological, and tissue tropism differences that could explain differences in clinical disease and viral transmission.
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Meliopoulos
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Erik A
authors.initials: EA
authors.lastname: Karlsson
authors.affiliation: Animal Resource Center, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Kercher
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Troy
authors.initials: T
authors.lastname: Cline
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Freiden
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Susu
authors.initials: S
authors.lastname: Duan
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Vogel
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Webby
authors.affiliation: State Key Laboratory of Emerging Infectious Diseases and Center of Influenza Research, University of Hong Kong, Hong Kong, China International Institute of Infection and Immunity, Shantou University Medical College, Shantou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Guan
authors.affiliation: State Key Laboratory of Emerging Infectious Diseases and Center of Influenza Research, University of Hong Kong, Hong Kong, China International Institute of Infection and Immunity, Shantou University Medical College, Shantou, China.
authors.forename: Malik
authors.initials: M
authors.lastname: Peiris
authors.affiliation: Animal Resource Center, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Thomas
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA stacey.schultz-cherry@stjude.org.
authors.forename: Stacey
authors.initials: S
authors.lastname: Schultz-Cherry
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism* / Q000633:toxicity; D004195:Disease Models, Animal; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology*; D064766:Influenza A Virus, H7N9 Subtype / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D007251:Influenza, Human / Q000821:virology*; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000821:virology*; D016019:Survival Analysis; D056189:Viral Tropism
chemical_list: D016207:Cytokines