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Transcriptional analysis of immune-related gene expression in p53-deficient mice with increased susceptibility to influenza A virus infection.
- Source :
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BMC medical genomics [BMC Med Genomics] 2015 Aug 18; Vol. 8, pp. 52. Date of Electronic Publication: 2015 Aug 18. - Publication Year :
- 2015
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Abstract
- Background: p53 is a tumor suppressor that contributes to the host immune response against viral infections in addition to its well-established protective role against cancer development. In response to influenza A virus (IAV) infection, p53 is activated and plays an essential role in inhibiting IAV replication. As a transcription factor, p53 regulates the expression of a range of downstream responsive genes either directly or indirectly in response to viral infection. We compared the expression profiles of immune-related genes between IAV-infected wild-type p53 (p53WT) and p53-deficient (p53KO) mice to gain an insight into the basis of p53-mediated antiviral response.<br />Methods: p53KO and p53WT mice were infected with influenza A/Puerto Rico/8/1934 (PR8) strain. Clinical symptoms and body weight changes were monitored daily. Lung specimens of IAV-infected mice were collected for analysis of virus titers and gene expression profiles. The difference in immune-related gene expression levels between IAV-infected p53KO and p53WT mice was comparatively determined using microarray analysis and confirmed by quantitative real-time reverse transcription polymerase chain reaction.<br />Results: p53KO mice showed an increased susceptibility to IAV infection compared to p53WT mice. Microarray analysis of gene expression profiles in the lungs of IAV-infected mice indicated that the increased susceptibility was associated with significantly changed expression levels in a range of immune-related genes in IAV-infected p53KO mice. A significantly attenuated expression of Ifng (encoding interferon (IFN)-gamma), Irf7 (encoding IFN regulator factor 7), and antiviral genes, such as Mx2 and Eif2ak2 (encoding PKR), were observed in IAV-infected p53KO mice, suggesting an impaired IFN-mediated immune response against IAV infection in the absence of p53. In addition, dysregulated expression levels of proinflammatory cytokines and chemokines, such as Ccl2 (encoding MCP-1), Cxcl9, Cxcl10 (encoding IP-10), and Tnf, were detected in IAV-infected p53KO mice during early IAV infection, reflecting an aberrant inflammatory response.<br />Conclusion: Lack of p53 resulted in the impaired expression of genes involved in IFN signaling and the dysregulated expression of cytokine and chemokine genes in IAV-infected mice, suggesting an essential role of p53 in the regulation of antiviral and inflammatory responses during IAV infection.
- Subjects :
- Animals
Cytokines genetics
Cytokines immunology
Disease Susceptibility
Gene Expression Profiling
Influenza A Virus, H1N1 Subtype genetics
Mice
Mice, Knockout
Orthomyxoviridae Infections genetics
Signal Transduction genetics
Transcription, Genetic genetics
Tumor Suppressor Protein p53 immunology
Gene Expression Regulation immunology
Influenza A Virus, H1N1 Subtype immunology
Orthomyxoviridae Infections immunology
Signal Transduction immunology
Transcription, Genetic immunology
Tumor Suppressor Protein p53 deficiency
Subjects
Details
- Language :
- English
- ISSN :
- 1755-8794
- Volume :
- 8
- Database :
- MEDLINE
- Journal :
- BMC medical genomics
- Publication Type :
- Academic Journal
- Accession number :
- 26282854
- Full Text :
- https://doi.org/10.1186/s12920-015-0127-8