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 Wang (1) , Shijian Zhang (1, 2, 3) , Hongbing Jiang (1) , Jinlan Wang (1) , Leiyun Weng (1) , Yingying Mao (1) , Satoshi Sekiguchi (4) , Fumihiko Yasui (4) , Michinori Kohara (4) , Philippe Buchy (5) , Vincent Deubel (5) , Ke Xu (1) , Bing Sun (1) , Tetsuya Toyoda (1, 4)

1 LMVI - Key Laboratory of Molecular Virology & Immunology
2 Shanghai Medical College of Fudan University
3 Roche R&D Center China LTD
4 Department of Microbiology and Cell Biology
5 Institut Pasteur du Cambodge

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.

Mots clés: Influenza virus; PA; transcription; apoptosis; interferon

Domaines: Virologie

Qiang Wang, Shijian Zhang, Hongbing Jiang, Jinlan Wang, Leiyun Weng, et al.. 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, 2012, 9, pp.106. ⟨10.1186/1743-422X-9-106⟩. ⟨pasteur-00782996⟩