tetano
Editor, Senior Moderator
Biochem Biophys Res Commun. 2014 Jun 27. pii: S0006-291X(14)01183-8. doi: 10.1016/j.bbrc.2014.06.109. [Epub ahead of print]
Inhibition of influenza virus infection and hemagglutinin cleavage by the protease inhibitor HAI-2.
Hamilton BS1, Chung C1, Cyphers SY1, Rinaldi VD1, Marcano VC1, Whittaker GR2.
Author information
Abstract
Influenza virus remains a significant concern to public health, with the continued potential for a high fatality pandemic. Vaccination and antiviral therapeutics are effective measures to circumvent influenza virus infection, however, multiple strains have emerged that are resistant to the antiviral therapeutics currently on the market. With this considered, investigation of alternative antiviral therapeutics is being conducted. One such approach is to inhibit cleavage activation of the influenza virus hemagglutinin (HA), which is an essential step in the viral replication cycle that permits viral-endosome fusion. Therefore, targeting trypsin-like, host proteases responsible for HA cleavage in vivo may prove to be an effective therapeutic. Hepatocyte growth factor activator inhibitor 2 (HAI-2) is naturally expressed in the respiratory tract and is a potent inhibitor of trypsin-like serine proteases, some of which have been determined to cleave HA. In this study, we demonstrate that HAI-2 is an effective inhibitor of cleavage of HA from the human-adapted H1 and H3 subtypes. HAI-2 inhibited influenza virus H1N1 infection in cell culture, and HAI-2 administration showed protection in a mouse model of influenza. HAI-2 has the potential to be an effective, alternative antiviral therapeutic for influenza.
Copyright ? 2014. Published by Elsevier Inc.
KEYWORDS:
HAI-2; Hemagglutinin; Influenza virus; Protease inhibitor
PMID:
24978308
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24978308
Inhibition of influenza virus infection and hemagglutinin cleavage by the protease inhibitor HAI-2.
Hamilton BS1, Chung C1, Cyphers SY1, Rinaldi VD1, Marcano VC1, Whittaker GR2.
Author information
Abstract
Influenza virus remains a significant concern to public health, with the continued potential for a high fatality pandemic. Vaccination and antiviral therapeutics are effective measures to circumvent influenza virus infection, however, multiple strains have emerged that are resistant to the antiviral therapeutics currently on the market. With this considered, investigation of alternative antiviral therapeutics is being conducted. One such approach is to inhibit cleavage activation of the influenza virus hemagglutinin (HA), which is an essential step in the viral replication cycle that permits viral-endosome fusion. Therefore, targeting trypsin-like, host proteases responsible for HA cleavage in vivo may prove to be an effective therapeutic. Hepatocyte growth factor activator inhibitor 2 (HAI-2) is naturally expressed in the respiratory tract and is a potent inhibitor of trypsin-like serine proteases, some of which have been determined to cleave HA. In this study, we demonstrate that HAI-2 is an effective inhibitor of cleavage of HA from the human-adapted H1 and H3 subtypes. HAI-2 inhibited influenza virus H1N1 infection in cell culture, and HAI-2 administration showed protection in a mouse model of influenza. HAI-2 has the potential to be an effective, alternative antiviral therapeutic for influenza.
Copyright ? 2014. Published by Elsevier Inc.
KEYWORDS:
HAI-2; Hemagglutinin; Influenza virus; Protease inhibitor
PMID:
24978308
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24978308