tetano
Editor, Senior Moderator
Journal of Virology
Published ahead of print 18 July 2012, doi: 10.1128/JVI.00306-12
Cleavage Activation of the Human-Adapted Influenza Virus Subtypes by Matriptase Reveals Both Subtype- and Strain-Specificity
Brian S. Hamilton,
David W. J. Gludish and
Gary R. Whittaker*
+ Author Affiliations
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca NY 14853 and New York Center of Excellence for Influenza Research and Surveillance, University of Rochester Medical Center, Rochester NY 14627
ABSTRACT
Cleavage activation of the hemagglutinin (HA) precursor is an essential step in the influenza virus replication cycle that is driven by host cell proteases. HA cleavage activation is required for virus-endosome membrane fusion and the subsequent release of the influenza genome into the cytoplasm. Previous studies have determined that HA cleavage is most likely driven by either membrane-bound or extracellular trypsin-like proteases that reside in the respiratory tract. However, there is still uncertainty regarding which proteases are critical for HA cleavage in vivo. Therefore, further investigation of HA cleavage activation is needed in order to gain insight into the critical proteases involved. Matriptase is a member of the type II transmembrane serine protease family that is highly expressed in a membrane-bound form throughout the respiratory tract. One feature of matriptase is that, once activated, the catalytic domain is secreted into the extracellular space and so serves as a functional extracellular protease. In this study, we have determined that the secreted, catalytic domain of matriptase has the ability to cleave and activate HA from the influenza H1 subtype, but not the H2 and H3 subtypes. Furthermore, matriptase selectively cleaved the HA of particular strains within the H1 subtype, revealing both subtype- and H1 strain-specificity. Matriptase was also found to activate thrombolytic zymogens that have been shown to cleave and activate the influenza HA. Our data demonstrate that matriptase has the ability to cleave HA directly, or indirectly by activating HA-cleaving zymogens.
http://jvi.asm.org/content/early/2012/07/12/JVI.00306-12.abstract
Published ahead of print 18 July 2012, doi: 10.1128/JVI.00306-12
Cleavage Activation of the Human-Adapted Influenza Virus Subtypes by Matriptase Reveals Both Subtype- and Strain-Specificity
Brian S. Hamilton,
David W. J. Gludish and
Gary R. Whittaker*
+ Author Affiliations
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca NY 14853 and New York Center of Excellence for Influenza Research and Surveillance, University of Rochester Medical Center, Rochester NY 14627
ABSTRACT
Cleavage activation of the hemagglutinin (HA) precursor is an essential step in the influenza virus replication cycle that is driven by host cell proteases. HA cleavage activation is required for virus-endosome membrane fusion and the subsequent release of the influenza genome into the cytoplasm. Previous studies have determined that HA cleavage is most likely driven by either membrane-bound or extracellular trypsin-like proteases that reside in the respiratory tract. However, there is still uncertainty regarding which proteases are critical for HA cleavage in vivo. Therefore, further investigation of HA cleavage activation is needed in order to gain insight into the critical proteases involved. Matriptase is a member of the type II transmembrane serine protease family that is highly expressed in a membrane-bound form throughout the respiratory tract. One feature of matriptase is that, once activated, the catalytic domain is secreted into the extracellular space and so serves as a functional extracellular protease. In this study, we have determined that the secreted, catalytic domain of matriptase has the ability to cleave and activate HA from the influenza H1 subtype, but not the H2 and H3 subtypes. Furthermore, matriptase selectively cleaved the HA of particular strains within the H1 subtype, revealing both subtype- and H1 strain-specificity. Matriptase was also found to activate thrombolytic zymogens that have been shown to cleave and activate the influenza HA. Our data demonstrate that matriptase has the ability to cleave HA directly, or indirectly by activating HA-cleaving zymogens.
http://jvi.asm.org/content/early/2012/07/12/JVI.00306-12.abstract