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Published in: Virology Journal 1/2012

Open Access 01-12-2012 | Research

PA from an H5N1 highly pathogenic avian influenza virus activates viral transcription and replication and induces apoptosis and interferon expression at an early stage of infection

Authors: Qiang Wang, Shijian Zhang, Hongbing Jiang, Jinlan Wang, Leiyun Weng, Yingying Mao, Satoshi Sekiguchi, Fumihiko Yasui, Michinori Kohara, Philippe Buchy, Vincent Deubel, Ke Xu, Bing Sun, Tetsuya Toyoda

Published in: Virology Journal | Issue 1/2012

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Abstract

Background

Although gene exchange is not likely to occur freely, reassortment between the H5N1 highly pathogenic avian influenza virus (HPAIV) and currently circulating human viruses is a serious concern. The PA polymerase subunit of H5N1 HPAIV was recently reported to activate the influenza replicon activity.

Methods

The replicon activities of PR8 and WSN strains (H1N1) of influenza containing PA from HPAIV A/Cambodia/P0322095/2005 (H5N1) and the activity of the chimeric RNA polymerase were analyzed. A reassortant WSN virus containing the H5N1 Cambodia PA (C-PA) was then reconstituted and its growth in cells and pathogenicity in mice examined. The interferon promoter, TUNEL, and caspase 3, 8, and 9 activities of C-PA-infected cells were compared with those of WSN-infected cells.

Results

The activity of the chimeric RNA polymerase was slightly higher than that of WSN, and C-PA replicated better than WSN in cells. However, the multi-step growth of C-PA and its pathogenicity in mice were lower than those of WSN. The interferon promoter, TUNEL, and caspase 3, 8, and 9 activities were strongly induced in early infection in C-PA-infected cells but not in WSN-infected cells.

Conclusions

Apoptosis and interferon were strongly induced early in C-PA infection, which protected the uninfected cells from expansion of viral infection. In this case, these classical host-virus interactions contributed to the attenuation of this strongly replicating virus.
Appendix
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Metadata
Title
PA from an H5N1 highly pathogenic avian influenza virus activates viral transcription and replication and induces apoptosis and interferon expression at an early stage of infection
Authors
Qiang Wang
Shijian Zhang
Hongbing Jiang
Jinlan Wang
Leiyun Weng
Yingying Mao
Satoshi Sekiguchi
Fumihiko Yasui
Michinori Kohara
Philippe Buchy
Vincent Deubel
Ke Xu
Bing Sun
Tetsuya Toyoda
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2012
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/1743-422X-9-106

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