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DC Field | Value | Language |
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dc.contributor.author | Fan, Y | - |
dc.contributor.author | Mok, C | - |
dc.contributor.author | Wai, M | - |
dc.contributor.author | Zhang, Y | - |
dc.contributor.author | Nal, B | - |
dc.contributor.author | Kien, F | - |
dc.contributor.author | Bruzzone, R | - |
dc.contributor.author | Sanyal, S | - |
dc.date.accessioned | 2017-03-03T12:01:57Z | - |
dc.date.available | 2017-03-03T12:01:57Z | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | The Journal of Biological Chemistry, pp-1-43, (2017) | en_US |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | http://bura.brunel.ac.uk/handle/2438/14181 | - |
dc.description.abstract | To identify new host factors that modulate the replication of influenza A virus, we performed a yeast two-hybrid screen using the cytoplasmic tail of matrix protein 2 from the highly pathogenic H5N1 strain. The screen revealed a high-score interaction with cyclin D3, a key regulator of cell cycle early G1 phase. M2-cyclin D3 interaction was validated through GST pull-down and recapitulated in influenza A/WSN/33-infected cells. Knockdown of Ccnd3 by small interfering RNA significantly enhanced virus progeny titers in cell culture supernatants. Interestingly, the increase in virus production was due to cyclin D3 deficiency per se, and not merely a consequence of cell cycle deregulation. A combined knockdown of Ccnd3 and Rb1, which rescued cell cycle progression into the S phase, failed to normalize virus production. Infection by IAV triggered redistribution of cyclin D3 from the nucleus to the cytoplasm followed by its proteasomal degradation. When over-expressed in HEK 293T cells cyclin D3 impaired binding of M2 with M1, which is essential for proper assembly of progeny virions, lending further support to its role as a putative restriction factor. Our study describes the identification and characterization of cyclin D3 as a novel interactor of influenza A virus M2 protein. We hypothesize that competitive inhibition of M1-M2 interaction by cyclin D3 impairs infectious virion formation and results in attenuated virus production. In addition, we provide mechanistic insights into the dynamic interplay of influenza virus with the host cell cycle machinery during infection. | en_US |
dc.description.sponsorship | This work was supported by the Research Fund for the Control of Infectious Diseases (Grant RFCID 11101332) and the Area of Excellence Scheme of the University Grants Committee (Grant AoE/M-12/06) and partially supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. T11-705/14N). | en_US |
dc.language.iso | en | en_US |
dc.publisher | American Society for Biochemistry and Molecular Biology | en_US |
dc.subject | Cyclin D3 | en_US |
dc.subject | M2 | en_US |
dc.subject | Restriction factor | en_US |
dc.subject | Cell cycle arrest | en_US |
dc.subject | Influenza | en_US |
dc.title | Cell cycle independent role of cyclin D3 in host restriction of influenza virus infection | en_US |
dc.type | Article | en_US |
dc.identifier.doi | http://dx.doi.org/10.1074/jbc.M117.776112 | - |
dc.relation.isPartOf | The Journal of biological chemistry | - |
pubs.publication-status | Accepted | - |
Appears in Collections: | Dept of Life Sciences Research Papers |
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FullText.pdf | 3.75 MB | Adobe PDF | View/Open |
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