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PA from an H5N1 highly pathogenic avian influenza virus activates viral transcription and replication and induces apoptosis and interferon expression

tetano

Editor, Senior Moderator
Virol J. 2012 Jun 8;9(1):106. [Epub ahead of print]
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.
Wang Q, Zhang S, Jiang H, Wang J, Weng L, Mao Y, Sekiguchi S, Yasui F, Kohara M, Buchy P, Deubel V, Xu K, Sun B, Toyoda T.
Abstract

ABSTRACT:
BACKGROUND:

Although gene exchange is not likely to occur freely, reassortment between the H5N1 highlypathogenic avian influenza virus (HPAIV) and currently circulating human viruses is aserious concern. The PA polymerase subunit of H5N1 HPAIV was recently reported toactivate the influenza replicon activity.
METHODS:

The replicon activities of PR8 and WSN strains (H1N1) of influenza containing PA fromHPAIV A/Cambodia/P0322095/2005 (H5N1) and the activity of the chimeric RNApolymerase were analyzed. A reassortant WSN virus containing the H5N1 Cambodia PA (CPA)was then reconstituted and its growth in cells and pathogenicity in mice examined. Theinterferon promoter, TUNEL, and caspase 3, 8, and 9 activities of C-PA-infected cells werecompared with those of WSN-infected cells.
RESULTS:

The activity of the chimeric RNA polymerase was slightly higher than that of WSN, and CPAreplicated better than WSN in cells. However, the multi-step growth of C-PA and itspathogenicity in mice were lower than those of WSN. The interferon promoter, TUNEL, andcaspase 3, 8, and 9 activities were strongly induced in early infection in C-PA-infected cellsbut not in WSN-infected cells.
CONCLUSIONS:

Apoptosis and interferon were strongly induced early in C-PA infection, which protected theuninfected cells from expansion of viral infection. In this case, these classical host-virusinteractions contributed to the attenuation of this strongly replicating virus.

PMID:
22681768
[PubMed - as supplied by publisher]

Free full text

http://www.ncbi.nlm.nih.gov/pubmed/22681768
 
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