tetano
Editor, Senior Moderator
J Virol. 2013 Oct 23. [Epub ahead of print]
Activation of Influenza A Viruses by Host Proteases from Swine Airway Epithelium.
Peitsch C, Klenk HD, Garten W, B?ttcher-Friebertsh?user E.
Source
Institute of Virology, Philipps University Marburg, Marburg, Germany.
Abstract
Pigs are important natural hosts of influenza A viruses and due to their susceptibility to swine, avian and human viruses, they may serve as intermediate hosts supporting adaptation and genetic reassortment. Cleavage of the influenza virus surface glycoprotein hemagglutinin (HA) by host cell proteases is essential for viral infectivity. Most influenza viruses, including human and swine viruses, are activated at a monobasic HA cleavage site, and we previously identified TMPRSS2 and HAT as relevant proteases present in human airways.We investigated proteolytic activation of influenza viruses in primary tracheal and bronchial epithelial cells from pigs (PTEC and PBEC). Human H1N1 and H3N2 viruses replicated efficiently in PTEC and PBEC and viruses containing cleaved HA were released from infected cells. Moreover, the cells supported proteolytic activation of HA at the stage of entry. We found that swine proteases homologous to TMPRSS2 and HAT, designated as swTMPRSS2 and swAT, respectively, were expressed in several parts of the porcine respiratory tract. Both proteases cloned from primary PBEC were shown to activate HA with monobasic cleavage site upon co-expression and support multicycle replication of influenza viruses. swAT was predominantly localised at the plasma membrane, where it was present as an active protease that mediated activation of incoming virus. In contrast, swTMPRSS2 accumulated in the trans-Golgi network, suggesting that it cleaves HA in this compartment. In conclusion, our data show that HA activation in the porcine airways may occur by similar proteases and at similar stages of the viral life cycle as in human airways.
PMID:
24155384
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24155384
Activation of Influenza A Viruses by Host Proteases from Swine Airway Epithelium.
Peitsch C, Klenk HD, Garten W, B?ttcher-Friebertsh?user E.
Source
Institute of Virology, Philipps University Marburg, Marburg, Germany.
Abstract
Pigs are important natural hosts of influenza A viruses and due to their susceptibility to swine, avian and human viruses, they may serve as intermediate hosts supporting adaptation and genetic reassortment. Cleavage of the influenza virus surface glycoprotein hemagglutinin (HA) by host cell proteases is essential for viral infectivity. Most influenza viruses, including human and swine viruses, are activated at a monobasic HA cleavage site, and we previously identified TMPRSS2 and HAT as relevant proteases present in human airways.We investigated proteolytic activation of influenza viruses in primary tracheal and bronchial epithelial cells from pigs (PTEC and PBEC). Human H1N1 and H3N2 viruses replicated efficiently in PTEC and PBEC and viruses containing cleaved HA were released from infected cells. Moreover, the cells supported proteolytic activation of HA at the stage of entry. We found that swine proteases homologous to TMPRSS2 and HAT, designated as swTMPRSS2 and swAT, respectively, were expressed in several parts of the porcine respiratory tract. Both proteases cloned from primary PBEC were shown to activate HA with monobasic cleavage site upon co-expression and support multicycle replication of influenza viruses. swAT was predominantly localised at the plasma membrane, where it was present as an active protease that mediated activation of incoming virus. In contrast, swTMPRSS2 accumulated in the trans-Golgi network, suggesting that it cleaves HA in this compartment. In conclusion, our data show that HA activation in the porcine airways may occur by similar proteases and at similar stages of the viral life cycle as in human airways.
PMID:
24155384
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24155384