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

Virology Journal

Tetsuya Toyoda⁶  Bing Sun⁵  Ke Xu⁵  Vincent Deubel³  Philippe Buchy³  Michinori Kohara⁴  Fumihiko Yasui⁴  Satoshi Sekiguchi⁴  Yingying Mao¹  Leiyun Weng¹  Jinlan Wang¹  Hongbing Jiang¹  Shijian Zhang²  Qiang Wang¹ 

[1] Units of Viral Genome Regulation, the Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, 411 Hefei Road, 200025, Shanghai, P. R. China;Roche R&D Center China LTD, 720 Cai Lun Road, Building 5, Pudong, Shanghai, 201203, P. R. China;Institut Pasteur in Cambodia, 5 Monivong Blvd, P.O. Box 983, Phnom Penh, Cambodia;Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Biology, 3-18-22 Honkomagome, Bunkyo-Ku, Tokyo, 113-8613, Japan;Units of Molecular Virology, the Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, 411 Hefei Road, 200025, Shanghai, P. R. China;Choju Medical Institute, Fukushimura Hospital, 19-14 Azanakayama, Noyori-cho, Toyohashi, Aichi, 441-8124, Japan

关键词: Interferon;    Apoptosis;    Replication;    Transcription;    PA;    Influenza virus;   

Others  :  1154593
DOI  :  10.1186/1743-422X-9-106

 received in 2011-10-14, accepted in 2012-05-21,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Wang et al.; licensee BioMed Central Ltd.

【 图 表 】

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