TMPRSS2 Independency for Haemagglutinin Cleavage In Vivo Differentiates Influenza B Virus from Influenza A Virus.

Kouji Sakai,Yuko Sato,Makoto Takeda,Ikuyo Takayama,Hideki Hasegawa,Yasushi Ami,Masato Tashiro,Noriko Nakajima,Katsuhiro Komase,Kazuaki Takehara,Masaki Anraku,Takato Odagiri,Natthanan Sangsriratanakul,Miyuki Komura,Minori Kitazawa,Hideki Asanuma,Emi Takashita,Katsuhiro Nakajima

doi:10.1038/srep29430

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.

Highlights

Influenza B virus (IBV) is classified into the same family, Orthomyxoviridae, as influenza A virus (IAV)[1]
Compared with efforts for IAV, only limited data are available for HA cleavage in IBV strains
Further analyses using cell cultures demonstrated that TMPRSS2 activates IBV HA as well as IAV HA11

Summary

Introduction

Influenza B virus (IBV) is classified into the same family, Orthomyxoviridae, as influenza A virus (IAV)[1]. Both viruses cause seasonal influenza, and the clinical manifestations of the infections are indistinguishable. They differ in their antigenic diversities and host ranges. The HA proteins of both IAV and IBV are synthesized as inactive precursors, and their proteolytic cleavage is a prerequisite for the HA conformational changes essential for virus infectivity. H3N2, H1N1, and H7N9 IAV strains replicated very poorly in TMPRSS2 KO mice owing to insufficient HA cleavage in these mice[8,9,10]. The role of TMPRSS2 for the in vivo replication of IBV was examined

Methods

Results

Conclusion