A mutant H3N2 influenza virus uses an alternative activation mechanism in TMPRSS2 knockout mice by loss of an oligosaccharide in the hemagglutinin stalk region

Kouji Sakai; Tsuyoshi Sekizuka; Yasushi Ami; Noriko Nakajima; Minori Kitazawa; Yuko Sato; Katsuhiro Nakajima; Masaki Anraku; Toru Kubota; Katsuhiro Komase; Kazuaki Takehara; Hideki Hasegawa; Takato Odagiri; Masato Tashiro; Makoto Kuroda; Makoto Takeda

doi:10.1128/JVI.00124-15

A mutant H3N2 influenza virus uses an alternative activation mechanism in TMPRSS2 knockout mice by loss of an oligosaccharide in the hemagglutinin stalk region

J Virol. 2015 May;89(9):5154-8. doi: 10.1128/JVI.00124-15. Epub 2015 Feb 11.

Authors

Affiliations

¹ Department of Virology 3, National Institute of Infectious Diseases, Tokyo, Japan [email protected].
² Laboratory of Bacterial Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan.
³ Division of Experimental Animal Research, National Institute of Infectious Diseases, Tokyo, Japan.
⁴ Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
⁵ 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.
⁶ Department of Virology 3, National Institute of Infectious Diseases, Tokyo, Japan.
⁷ Laboratory of Animal Health, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan.
⁸ Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo, Japan.

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).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Hemagglutinin Glycoproteins, Influenza Virus / genetics
Hemagglutinin Glycoproteins, Influenza Virus / metabolism*
Influenza A Virus, H3N2 Subtype / genetics*
Influenza A Virus, H3N2 Subtype / growth & development
Influenza A Virus, H3N2 Subtype / physiology*
Mice, Knockout
Oligosaccharides / genetics
Oligosaccharides / metabolism*
Protein Processing, Post-Translational*
Serine Endopeptidases / deficiency*
Virulence
Virus Internalization

Substances

Hemagglutinin Glycoproteins, Influenza Virus
Oligosaccharides
Serine Endopeptidases
TMPRSS2 protein, mouse

Associated data

PDB/5HMG