Caspase-1 deficient mice are more susceptible to influenza A virus infection with PA variation
Reassortment within polymerase genes causes changes in the pathogenicity of influenza A viruses. We previously reported that the 2009 pH1N1 PA enhanced the pathogenicity of seasonal H1N1. We examined the effects of the PA gene from the HPAI H5N1 following its introduction into currently circulating...
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| Vydané v: | The Journal of infectious diseases Ročník 208; číslo 11; s. 1898 |
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| Hlavní autori: | , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
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01.12.2013
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| ISSN: | 1537-6613, 1537-6613 |
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| Abstract | Reassortment within polymerase genes causes changes in the pathogenicity of influenza A viruses. We previously reported that the 2009 pH1N1 PA enhanced the pathogenicity of seasonal H1N1. We examined the effects of the PA gene from the HPAI H5N1 following its introduction into currently circulating seasonal influenza viruses.
To evaluate the role of H5N1 PA in altering the virulence of seasonal influenza viruses, we generated a recombinant seasonal H3N2 (3446) that expressed the H5N1 PA protein (VPA) and evaluated the RNP activity, growth kinetics, and pathogenicity of the reassortant virus in mice.
Compared with the wild-type 3446 virus, the substitution of the H5N1 PA gene into the 3446 virus (VPA/3446) resulted in increased RNP activity and an increased replication rate in A549 cells. The recombinant VPA/3446 virus also caused more severe pneumonia in Casp 1(-/-) mice than in IL1β(-/-) and wild-type B6 mice.
Although the PA from H5N1 is incidentally compatible with a seasonal H3N2 backbone, the H5N1 PA affected the virulence of seasonal H3N2, particularly in inflammasome-related innate immunity deficient mice. These findings highlight the importance of monitoring PA reassortment in seasonal flu, and confirm the role of the Caspase-1 gene in influenza pathogenesis. |
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| AbstractList | Reassortment within polymerase genes causes changes in the pathogenicity of influenza A viruses. We previously reported that the 2009 pH1N1 PA enhanced the pathogenicity of seasonal H1N1. We examined the effects of the PA gene from the HPAI H5N1 following its introduction into currently circulating seasonal influenza viruses.
To evaluate the role of H5N1 PA in altering the virulence of seasonal influenza viruses, we generated a recombinant seasonal H3N2 (3446) that expressed the H5N1 PA protein (VPA) and evaluated the RNP activity, growth kinetics, and pathogenicity of the reassortant virus in mice.
Compared with the wild-type 3446 virus, the substitution of the H5N1 PA gene into the 3446 virus (VPA/3446) resulted in increased RNP activity and an increased replication rate in A549 cells. The recombinant VPA/3446 virus also caused more severe pneumonia in Casp 1(-/-) mice than in IL1β(-/-) and wild-type B6 mice.
Although the PA from H5N1 is incidentally compatible with a seasonal H3N2 backbone, the H5N1 PA affected the virulence of seasonal H3N2, particularly in inflammasome-related innate immunity deficient mice. These findings highlight the importance of monitoring PA reassortment in seasonal flu, and confirm the role of the Caspase-1 gene in influenza pathogenesis. Reassortment within polymerase genes causes changes in the pathogenicity of influenza A viruses. We previously reported that the 2009 pH1N1 PA enhanced the pathogenicity of seasonal H1N1. We examined the effects of the PA gene from the HPAI H5N1 following its introduction into currently circulating seasonal influenza viruses.BACKGROUNDReassortment within polymerase genes causes changes in the pathogenicity of influenza A viruses. We previously reported that the 2009 pH1N1 PA enhanced the pathogenicity of seasonal H1N1. We examined the effects of the PA gene from the HPAI H5N1 following its introduction into currently circulating seasonal influenza viruses.To evaluate the role of H5N1 PA in altering the virulence of seasonal influenza viruses, we generated a recombinant seasonal H3N2 (3446) that expressed the H5N1 PA protein (VPA) and evaluated the RNP activity, growth kinetics, and pathogenicity of the reassortant virus in mice.METHODSTo evaluate the role of H5N1 PA in altering the virulence of seasonal influenza viruses, we generated a recombinant seasonal H3N2 (3446) that expressed the H5N1 PA protein (VPA) and evaluated the RNP activity, growth kinetics, and pathogenicity of the reassortant virus in mice.Compared with the wild-type 3446 virus, the substitution of the H5N1 PA gene into the 3446 virus (VPA/3446) resulted in increased RNP activity and an increased replication rate in A549 cells. The recombinant VPA/3446 virus also caused more severe pneumonia in Casp 1(-/-) mice than in IL1β(-/-) and wild-type B6 mice.RESULTSCompared with the wild-type 3446 virus, the substitution of the H5N1 PA gene into the 3446 virus (VPA/3446) resulted in increased RNP activity and an increased replication rate in A549 cells. The recombinant VPA/3446 virus also caused more severe pneumonia in Casp 1(-/-) mice than in IL1β(-/-) and wild-type B6 mice.Although the PA from H5N1 is incidentally compatible with a seasonal H3N2 backbone, the H5N1 PA affected the virulence of seasonal H3N2, particularly in inflammasome-related innate immunity deficient mice. These findings highlight the importance of monitoring PA reassortment in seasonal flu, and confirm the role of the Caspase-1 gene in influenza pathogenesis.CONCLUSIONSAlthough the PA from H5N1 is incidentally compatible with a seasonal H3N2 backbone, the H5N1 PA affected the virulence of seasonal H3N2, particularly in inflammasome-related innate immunity deficient mice. These findings highlight the importance of monitoring PA reassortment in seasonal flu, and confirm the role of the Caspase-1 gene in influenza pathogenesis. |
| Author | Huang, Peng-Nien Chen, Chi-Jene Yen, Chia-Tsui Kuo, Rei-Lin Shih, Shin-Ru Lin, Sue-Jane Chang, Cheng-Kai Huang, Chih-Heng Yu, Cheng-Ping |
| Author_xml | – sequence: 1 givenname: Chih-Heng surname: Huang fullname: Huang, Chih-Heng organization: Research Center for Emerging Viral Infections – sequence: 2 givenname: Chi-Jene surname: Chen fullname: Chen, Chi-Jene – sequence: 3 givenname: Chia-Tsui surname: Yen fullname: Yen, Chia-Tsui – sequence: 4 givenname: Cheng-Ping surname: Yu fullname: Yu, Cheng-Ping – sequence: 5 givenname: Peng-Nien surname: Huang fullname: Huang, Peng-Nien – sequence: 6 givenname: Rei-Lin surname: Kuo fullname: Kuo, Rei-Lin – sequence: 7 givenname: Sue-Jane surname: Lin fullname: Lin, Sue-Jane – sequence: 8 givenname: Cheng-Kai surname: Chang fullname: Chang, Cheng-Kai – sequence: 9 givenname: Shin-Ru surname: Shih fullname: Shih, Shin-Ru |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/23901080$$D View this record in MEDLINE/PubMed |
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| Snippet | Reassortment within polymerase genes causes changes in the pathogenicity of influenza A viruses. We previously reported that the 2009 pH1N1 PA enhanced the... |
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| SubjectTerms | Animals Caspase 1 - metabolism Cell Line Disease Models, Animal Dogs Genetic Engineering Humans Immunity, Innate Influenza A Virus, H3N2 Subtype - genetics Influenza A Virus, H3N2 Subtype - immunology Influenza A Virus, H3N2 Subtype - pathogenicity Influenza A Virus, H5N1 Subtype - genetics Influenza A Virus, H5N1 Subtype - immunology Influenza A Virus, H5N1 Subtype - pathogenicity Influenza, Human - immunology Influenza, Human - virology Lung - pathology Lung - virology Mice Mice, Inbred C57BL Mice, Knockout Orthomyxoviridae Infections - immunology Orthomyxoviridae Infections - virology Reassortant Viruses RNA Replicase - genetics RNA Replicase - metabolism Specific Pathogen-Free Organisms Viral Proteins - genetics Viral Proteins - metabolism Virulence Virus Replication |
| Title | Caspase-1 deficient mice are more susceptible to influenza A virus infection with PA variation |
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