title: A mutant H3N2 influenza virus uses an alternative activation mechanism in TMPRSS2 knockout mice by loss of an oligosaccharide in the hemagglutinin stalk region.
abstract: The host protease TMPRSS2 plays an essential role in proteolytic activation of the influenza A virus (IAV) hemagglutinin (HA) protein possessing a monobasic cleavage site. However, after passages in TMPRSS2 knockout mice, an H3N2 subtype IAV began to undergo cleavage activation of HA, showing high virulence in the mice due to the loss of an oligosaccharide at position 8 in the HA stalk region. Thus, the H3N2 IAV acquired cleavability by an alternative HA activation mechanism/protease(s).
authors: Department of Virology 3, National Institute of Infectious Diseases, Tokyo, Japan ksakai@nih.go.jp.
authors: Kouji
authors: K
authors: Sakai
authors: Laboratory of Bacterial Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors: Tsuyoshi
authors: T
authors: Sekizuka
authors: Division of Experimental Animal Research, National Institute of Infectious Diseases, Tokyo, Japan.
authors: Yasushi
authors: Y
authors: Ami
authors: Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
authors: Noriko
authors: N
authors: Nakajima
authors: Department of Virology 3, National Institute of Infectious Diseases, Tokyo, Japan Laboratory of Animal Health, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan.
authors: Minori
authors: M
authors: Kitazawa
authors: Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
authors: Yuko
authors: Y
authors: Sato
authors: Department of Virology 3, National Institute of Infectious Diseases, Tokyo, Japan Laboratory of Animal Health, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan.
authors: Katsuhiro
authors: K
authors: Nakajima
authors: Department of Virology 3, National Institute of Infectious Diseases, Tokyo, Japan.
authors: Masaki
authors: M
authors: Anraku
authors: Department of Virology 3, National Institute of Infectious Diseases, Tokyo, Japan.
authors: Toru
authors: T
authors: Kubota
authors: Department of Virology 3, National Institute of Infectious Diseases, Tokyo, Japan.
authors: Katsuhiro
authors: K
authors: Komase
authors: Laboratory of Animal Health, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan.
authors: Kazuaki
authors: K
authors: Takehara
authors: Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
authors: Hideki
authors: H
authors: Hasegawa
authors: Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors: Takato
authors: T
authors: Odagiri
authors: Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors: Masato
authors: M
authors: Tashiro
authors: Laboratory of Bacterial Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors: Makoto
authors: M
authors: Kuroda
authors: Department of Virology 3, National Institute of Infectious Diseases, Tokyo, Japan.
authors: Makoto
authors: M
authors: Takeda
mesh_terms: D000818:Animals; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000378:metabolism*; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics* / Q000254:growth & development / Q000502:physiology*; D018345:Mice, Knockout; D009844:Oligosaccharides / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012697:Serine Endopeptidases / Q000172:deficiency*; D014774:Virulence; D053586:Virus Internalization
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D009844:Oligosaccharides; D012697:Serine Endopeptidases; C000588699:TMPRSS2 protein, mouse