Email updates

Keep up to date with the latest news and content from Virology Journal and BioMed Central.

Open Access Highly Accessed 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

Qiang Wang12, Shijian Zhang234, Hongbing Jiang2, Jinlan Wang2, Leiyun Weng2, Yingying Mao2, Satoshi Sekiguchi5, Fumihiko Yasui5, Michinori Kohara5, Philippe Buchy6, Vincent Deubel6, Ke Xu1, Bing Sun1 and Tetsuya Toyoda257*

Author Affiliations

1 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

2 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

3 Shanghai Medical College of Fudan University, Yixueyuan Road 138, Shanghai, 200032, P. R. China

4 Roche R&D Center China LTD, 720 Cai Lun Road, Building 5, Pudong, Shanghai, 201203, P. R. China

5 Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Biology, 3-18-22 Honkomagome, Bunkyo-Ku, Tokyo, 113-8613, Japan

6 Institut Pasteur in Cambodia, 5 Monivong Blvd, P.O. Box 983, Phnom Penh, Cambodia

7 Choju Medical Institute, Fukushimura Hospital, 19-14 Azanakayama, Noyori-cho, Toyohashi, Aichi, 441-8124, Japan

For all author emails, please log on.

Virology Journal 2012, 9:106  doi:10.1186/1743-422X-9-106

Published: 8 June 2012

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.

Keywords:
Influenza virus; PA; Transcription; Replication; Apoptosis; Interferon