title: Novel insights into proteolytic cleavage of influenza virus hemagglutinin.
abstract: The influenza virus hemagglutinin (HA) mediates the first essential step in the viral life cycle, virus entry into target cells. Influenza virus HA is synthesised as a precursor protein in infected cells and requires cleavage by host cell proteases to transit into an active form. Cleavage is essential for influenza virus infectivity and the HA-processing proteases are attractive targets for therapeutic intervention. It is well established that cleavage by ubiquitously expressed subtilisin-like proteases is a hallmark of highly pathogenic avian influenza viruses (HPAIV). In contrast, the nature of the proteases responsible for cleavage of HA of human influenza viruses and low pathogenic avian influenza viruses (LPAIV) is not well understood. Recent studies suggest that cleavage of HA of human influenza viruses might be a cell-associated event and might be facilitated by the type II transmembrane serine proteases (TTSPs) TMPRSS2, TMPRSS4 and human airway trypsin-like protease (HAT). Here, we will introduce the different concepts established for proteolytic activation of influenza virus HA, with a particular focus on the role of TTSPs, and we will discuss their implications for viral tropism, pathogenicity and antiviral intervention.
authors.affiliation: Institute of Virology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bertram
authors.forename: Ilona
authors.initials: I
authors.lastname: Glowacka
authors.forename: Imke
authors.initials: I
authors.lastname: Steffen
authors.forename: Annika
authors.initials: A
authors.lastname: Kühl
authors.forename: Stefan
authors.initials: S
authors.lastname: Pöhlmann
mesh_terms: D006389:Hemagglutinins, Viral / Q000378:metabolism*; D006801:Humans; D009975:Orthomyxoviridae / Q000502:physiology*; D010447:Peptide Hydrolases / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D053586:Virus Internalization
chemical_list: D006389:Hemagglutinins, Viral; C458881:hemagglutinin fusogenic peptide, influenza virus; D010447:Peptide Hydrolases