title: TMPRSS2 Independency for Haemagglutinin Cleavage In Vivo Differentiates Influenza B Virus from Influenza A Virus.
abstract: Influenza A and B viruses show clear differences in their host specificity and pandemic potential. Recent studies have revealed that the host protease TMPRSS2 plays an essential role for proteolytic activation of H1, H3, and H7 subtype strains of influenza A virus (IAV) in vivo. IAV possessing a monobasic cleavage site in the haemagglutinin (HA) protein replicates poorly in TMPRSS2 knockout mice owing to insufficient HA cleavage. In the present study, human isolates of influenza B virus (IBV) strains and a mouse-adapted IBV strain were analysed. The data showed that IBV successfully underwent HA cleavage in TMPRSS2 knockout mice, and that the mouse-adapted strain was fully pathogenic to these mice. The present data demonstrate a clear difference between IAV and IBV in their molecular mechanisms for spreading in vivo.
authors.affiliation: Department of Virology 3, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Sakai
authors.affiliation: Division of Experimental Animal Research, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ami
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Nakajima
authors.affiliation: Department of Virology 3, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.|Laboratory of Animal Health, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: Department of Virology 3, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.|Laboratory of Animal Health, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan.
authors.forename: Minori
authors.initials: M
authors.lastname: Kitazawa
authors.affiliation: Department of Microbiology, School of Medicine, Yokohama City University, Yokohama 236-0004, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Anraku
authors.affiliation: Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Takayama
authors.affiliation: Department of Virology 3, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.|Laboratory of Animal Health, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan.
authors.forename: Natthanan
authors.initials: N
authors.lastname: Sangsriratanakul
authors.affiliation: Department of Virology 3, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.|Laboratory of Animal Health, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Komura
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Asanuma
authors.affiliation: Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Takashita
authors.affiliation: Department of Virology 3, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Komase
authors.affiliation: Laboratory of Animal Health, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Takehara
authors.affiliation: Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Tashiro
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hasegawa
authors.affiliation: Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
authors.forename: Takato
authors.initials: T
authors.lastname: Odagiri
authors.affiliation: Department of Virology 3, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Takeda
mesh_terms: D000818:Animals; D006367:HeLa Cells; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry*; D058507:Host Specificity; D006801:Humans; D009980:Influenza A virus / Q000472:pathogenicity / Q000502:physiology*; D009981:Influenza B virus / Q000472:pathogenicity / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008958:Models, Molecular; D011487:Protein Conformation; D059748:Proteolysis; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D012697:Serine Endopeptidases; C000588699:TMPRSS2 protein, mouse