Early apoptosis of porcine alveolar macrophages limits avian influenza virus replication and pro-inflammatory dysregulation

Pigs are evidently more resistant to avian than swine influenza A viruses, mediated in part through frontline epithelial cells and alveolar macrophages (AM). Although porcine AM (PAM) are crucial in influenza virus control, their mode of control is unclear. To gain insight into the possible role of...

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Main Authors: Pengxiang Chang, Suresh V. Kuchipudi, Kenneth H. Mellits, Sujith Sebastian, Joe James, Jinhua Liu, Holly Shelton, Kin-Chow Chang
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Published: 2015
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Online Access:https://hdl.handle.net/2134/20615
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spelling rr-article-95677912015-01-01T00:00:00Z Early apoptosis of porcine alveolar macrophages limits avian influenza virus replication and pro-inflammatory dysregulation Pengxiang Chang (4099426) Suresh V. Kuchipudi (7211204) Kenneth H. Mellits (7214228) Sujith Sebastian (1247778) Joe James (7214231) Jinhua Liu (189844) Holly Shelton (202275) Kin-Chow Chang (64619) Mechanical engineering not elsewhere classified Viruses Avian flu H5N1 Pigs PB1-F2 Disease Infection Resistance Mechanical Engineering not elsewhere classified Pigs are evidently more resistant to avian than swine influenza A viruses, mediated in part through frontline epithelial cells and alveolar macrophages (AM). Although porcine AM (PAM) are crucial in influenza virus control, their mode of control is unclear. To gain insight into the possible role of PAM in the mediation of avian influenza virus resistance, we compared the host effects and replication of two avian (H2N3 and H6N1) and three mammalian (swine H1N1, human H1N1 and pandemic H1N1) influenza viruses in PAM. We found that PAM were readily susceptible to initial infection with all five avian and mammalian influenza viruses but only avian viruses caused early and extensive apoptosis (by 6 h of infection) resulting in reduced virus progeny and moderated pro-inflammation. Full length viral PB1-F2 present only in avian influenza viruses is a virulence factor that targets AM for mitochondrial-associated apoptotic cell death. With the use of reverse genetics on an avian H5N1 virus, we found that full length PB1-F2 contributed to increased apoptosis and pro-inflammation but not to reduced virus replication. Taken together, we propose that early apoptosis of PAM limits the spread of avian influenza viruses and that PB1-F2 could play a contributory role in the process. 2015-01-01T00:00:00Z Text Journal contribution 2134/20615 https://figshare.com/articles/journal_contribution/Early_apoptosis_of_porcine_alveolar_macrophages_limits_avian_influenza_virus_replication_and_pro-inflammatory_dysregulation/9567791 CC BY 4.0
institution Loughborough University
collection Figshare
topic Mechanical engineering not elsewhere classified
Viruses
Avian flu
H5N1
Pigs
PB1-F2
Disease
Infection
Resistance
Mechanical Engineering not elsewhere classified
spellingShingle Mechanical engineering not elsewhere classified
Viruses
Avian flu
H5N1
Pigs
PB1-F2
Disease
Infection
Resistance
Mechanical Engineering not elsewhere classified
Pengxiang Chang
Suresh V. Kuchipudi
Kenneth H. Mellits
Sujith Sebastian
Joe James
Jinhua Liu
Holly Shelton
Kin-Chow Chang
Early apoptosis of porcine alveolar macrophages limits avian influenza virus replication and pro-inflammatory dysregulation
description Pigs are evidently more resistant to avian than swine influenza A viruses, mediated in part through frontline epithelial cells and alveolar macrophages (AM). Although porcine AM (PAM) are crucial in influenza virus control, their mode of control is unclear. To gain insight into the possible role of PAM in the mediation of avian influenza virus resistance, we compared the host effects and replication of two avian (H2N3 and H6N1) and three mammalian (swine H1N1, human H1N1 and pandemic H1N1) influenza viruses in PAM. We found that PAM were readily susceptible to initial infection with all five avian and mammalian influenza viruses but only avian viruses caused early and extensive apoptosis (by 6 h of infection) resulting in reduced virus progeny and moderated pro-inflammation. Full length viral PB1-F2 present only in avian influenza viruses is a virulence factor that targets AM for mitochondrial-associated apoptotic cell death. With the use of reverse genetics on an avian H5N1 virus, we found that full length PB1-F2 contributed to increased apoptosis and pro-inflammation but not to reduced virus replication. Taken together, we propose that early apoptosis of PAM limits the spread of avian influenza viruses and that PB1-F2 could play a contributory role in the process.
format Default
Article
author Pengxiang Chang
Suresh V. Kuchipudi
Kenneth H. Mellits
Sujith Sebastian
Joe James
Jinhua Liu
Holly Shelton
Kin-Chow Chang
author_facet Pengxiang Chang
Suresh V. Kuchipudi
Kenneth H. Mellits
Sujith Sebastian
Joe James
Jinhua Liu
Holly Shelton
Kin-Chow Chang
author_sort Pengxiang Chang (4099426)
title Early apoptosis of porcine alveolar macrophages limits avian influenza virus replication and pro-inflammatory dysregulation
title_short Early apoptosis of porcine alveolar macrophages limits avian influenza virus replication and pro-inflammatory dysregulation
title_full Early apoptosis of porcine alveolar macrophages limits avian influenza virus replication and pro-inflammatory dysregulation
title_fullStr Early apoptosis of porcine alveolar macrophages limits avian influenza virus replication and pro-inflammatory dysregulation
title_full_unstemmed Early apoptosis of porcine alveolar macrophages limits avian influenza virus replication and pro-inflammatory dysregulation
title_sort early apoptosis of porcine alveolar macrophages limits avian influenza virus replication and pro-inflammatory dysregulation
publishDate 2015
url https://hdl.handle.net/2134/20615
_version_ 1799639504879878144