Influenza and SARS-coronavirus activating proteases TMPRSS2 and HAT are expressed at multiple sites in human respiratory and gastrointestinal tracts

The type II transmembrane serine proteases TMPRSS2 and HAT activate influenza viruses and the SARS-coronavirus (TMPRSS2) in cell culture and may play an important role in viral spread and pathogenesis in the infected host. However, it is at present largely unclear to what extent these proteases are...

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Bibliographic Details
Published in:PloS one 2012-04, Vol.7 (4), p.e35876-e35876
Main Authors: Bertram, Stephanie, Heurich, Adeline, Lavender, Hayley, Gierer, Stefanie, Danisch, Simon, Perin, Paula, Lucas, Jared M, Nelson, Peter S, Pöhlmann, Stefan, Soilleux, Elizabeth J
Format: Article
Language:English
Subjects:
Amino acids
Angiotensin-Converting Enzyme 2
Animals
Binding sites
Biology
Birds
Cell culture
Cell Line
Coronaviridae
Coronaviruses
Disease Reservoirs - veterinary
Disease Reservoirs - virology
Enzyme Activation
Enzymes
Epiglottis
Gastrointestinal system
Gastrointestinal Tract - enzymology
Gastrointestinal Tract - virology
Gene Expression
Human tissues
Humans
Infections
Influenza
Influenza viruses
Influenza, Human - enzymology
Influenza, Human - genetics
Influenza, Human - transmission
Influenza, Human - virology
Laboratories
Medical research
Medicine
Orthomyxoviridae - physiology
Pandemics
Pathogenesis
Peptidyl-Dipeptidase A - genetics
Peptidyl-Dipeptidase A - metabolism
Plasmids
Proteases
Proteins
Receptors, Virus - genetics
Receptors, Virus - metabolism
Respiratory System - enzymology
Respiratory System - virology
Respiratory tract
Serine
Serine Endopeptidases - genetics
Serine Endopeptidases - metabolism
Severe acute respiratory syndrome
Severe Acute Respiratory Syndrome - enzymology
Severe Acute Respiratory Syndrome - genetics
Severe Acute Respiratory Syndrome - transmission
Severe Acute Respiratory Syndrome - virology
Severe acute respiratory syndrome-related coronavirus - physiology
Sialic acids
Sialic Acids - metabolism
Swine
Tissues
Trachea
Virology
Viruses
Zoonoses
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Summary:The type II transmembrane serine proteases TMPRSS2 and HAT activate influenza viruses and the SARS-coronavirus (TMPRSS2) in cell culture and may play an important role in viral spread and pathogenesis in the infected host. However, it is at present largely unclear to what extent these proteases are expressed in viral target cells in human tissues. Here, we show that both HAT and TMPRSS2 are coexpressed with 2,6-linked sialic acids, the major receptor determinant of human influenza viruses, throughout the human respiratory tract. Similarly, coexpression of ACE2, the SARS-coronavirus receptor, and TMPRSS2 was frequently found in the upper and lower aerodigestive tract, with the exception of the vocal folds, epiglottis and trachea. Finally, activation of influenza virus was conserved between human, avian and porcine TMPRSS2, suggesting that this protease might activate influenza virus in reservoir-, intermediate- and human hosts. In sum, our results show that TMPRSS2 and HAT are expressed by important influenza and SARS-coronavirus target cells and could thus support viral spread in the human host.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0035876