tetano
Editor, Senior Moderator
J Virol. 2014 Aug 13. pii: JVI.01427-14. [Epub ahead of print]
DESC1 and MSPL activate influenza A viruses and emerging coronaviruses for host cell entry.
Zmora P1, Blazejewska P1, Moldenhauer AS1, Welsch K1, Nehlmeier I1, Wu Q2, Schneider H3, P?hlmann S4, Bertram S1.
Author information
Abstract
The type II transmembrane serine protease (TTSP) TMPRSS2 cleaves and activates the surface proteins of influenza and coronaviruses. Expression of TMPRSS2 is essential for spread and pathogenesis of H1N1 influenza viruses in mice. In contrast, H3N2 viruses are less dependent on TMPRSS2 for viral amplification, suggesting that these viruses might employ other TTSPs for their activation. Here, we analysed TTSPs, reported to be expressed in the respiratory system, for their ability to activate influenza and coronaviruses. We found that MSPL and, to a lesser degree DESC1, are expressed in human lung tissue and cleave and activate the spike proteins of the MERS- and SARS-coronavirus for cell-cell and virus-cell fusion. In addition, we show that these proteases support the spread of all influenza virus subtypes previously pandemic in humans. In sum, we identified two host cell proteases which could promote the amplification of influenza and emerging coronaviruses in humans and might constitute targets for antiviral intervention.
IMPORTANCE:
Activation of influenza viruses by host cell proteases is essential for viral infectivity and the responsible enzymes are potential targets for antiviral intervention. The present study demonstrates that two cellular serine proteases, DESC1 and MSPL, activate influenza viruses and emerging coronaviruses in cell culture and, due to their expression in human lung tissue, might promote viral spread in the infected host. Antiviral strategies aiming to prevent viral activation might thus need to encompass inhibitors targeting MSPL and DESC1.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
25122802
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25122802
DESC1 and MSPL activate influenza A viruses and emerging coronaviruses for host cell entry.
Zmora P1, Blazejewska P1, Moldenhauer AS1, Welsch K1, Nehlmeier I1, Wu Q2, Schneider H3, P?hlmann S4, Bertram S1.
Author information
Abstract
The type II transmembrane serine protease (TTSP) TMPRSS2 cleaves and activates the surface proteins of influenza and coronaviruses. Expression of TMPRSS2 is essential for spread and pathogenesis of H1N1 influenza viruses in mice. In contrast, H3N2 viruses are less dependent on TMPRSS2 for viral amplification, suggesting that these viruses might employ other TTSPs for their activation. Here, we analysed TTSPs, reported to be expressed in the respiratory system, for their ability to activate influenza and coronaviruses. We found that MSPL and, to a lesser degree DESC1, are expressed in human lung tissue and cleave and activate the spike proteins of the MERS- and SARS-coronavirus for cell-cell and virus-cell fusion. In addition, we show that these proteases support the spread of all influenza virus subtypes previously pandemic in humans. In sum, we identified two host cell proteases which could promote the amplification of influenza and emerging coronaviruses in humans and might constitute targets for antiviral intervention.
IMPORTANCE:
Activation of influenza viruses by host cell proteases is essential for viral infectivity and the responsible enzymes are potential targets for antiviral intervention. The present study demonstrates that two cellular serine proteases, DESC1 and MSPL, activate influenza viruses and emerging coronaviruses in cell culture and, due to their expression in human lung tissue, might promote viral spread in the infected host. Antiviral strategies aiming to prevent viral activation might thus need to encompass inhibitors targeting MSPL and DESC1.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
25122802
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25122802