Highly pathogenic avian influenza virus H5N1 controls type I IFN induction in chicken macrophage HD-11 cells: a polygenic trait that involves NS1 and the polymerase complex

Virology Journal

Artur Summerfield²  Nicolas Ruggli²  Yoshihiro Sakoda¹  Hervé R Moulin²  Matthias Liniger² 

[1] Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Japan;Institute of Virology and Immunoprophylaxis (IVI), Sensemattstrasse 293, CH-3147 Mittelhäusern, Switzerland

关键词: viral polymerase complex;    nonstructural protein 1;    type I interferon;    chicken HD-11 macrophage-like cell line;    H5N1 avian influenza A virus;   

Others  :  1155295
DOI  :  10.1186/1743-422X-9-7

 received in 2011-09-09, accepted in 2012-01-09,  发布年份 2012

【 摘 要 】

Background

Influenza A viruses are well characterized to antagonize type I IFN induction in infected mammalian cells. However, limited information is available for avian cells. It was hypothesised that avian influenza viruses (AIV) with distinct virulence may interact differently with the avian innate immune system. Therefore, the type I IFN responses induced by highly virulent and low virulent H5N1 AIV and reassortants thereof were analysed in chicken cells.

Results

The highly pathogenic (HP) AIV A/chicken/Yamaguchi/7/04 (H5N1) (Yama) did not induce type I IFN in infected chicken HD-11 macrophage-like cells. This contrasted with an NS1 mutant Yama virus (Yama-NS1^A144V) and with the attenuated H5N1 AIV A/duck/Hokkaido/Vac-1/04 (Vac) carrying the haemagglutinin (HA) of the Yama virus (Vac-Yama/HA), that both induced type I IFN in these cells. The substitution of the NS segment from Yama with that from Vac in the Yama backbone resulted in induction of type I IFN secretion in HD-11 cells. However, vice versa, the Yama NS segment did not prevent type I IFN induction by the Vac-Yama/HA virus. This was different with the PB1/PB2/PA segment reassortant Yama and Vac-Yama/HA viruses. Whereas the Yama virus with the Vac PB1/PB2/PA segments induced type I IFN in HD-11 cells, the Vac-Yama/HA virus with the Yama PB1/PB2/PA segments did not. As reported for mammalian cells, the expression of H5N1 PB2 inhibited the activation of the IFN-β promoter in chicken DF-1 fibroblast cells. Importantly, the Yama PB2 was more potent at inhibiting the IFN-β promoter than the Vac PB2.

Conclusions

The present study demonstrates that the NS1 protein and the polymerase complex of the HPAIV Yama act in concert to antagonize chicken type I IFN secretion in HD-11 cells. PB2 alone can also exert a partial inhibitory effect on type I IFN induction. In conclusion, the control of type I IFN induction by H5N1 HPAIV represents a complex phenotype that involves a particular viral gene constellation rather than a single viral protein. Collectively, these findings contribute to understand the high virulence of HPAIV H5N1 viruses observed in the chicken host.

【 授权许可】

   
2012 Liniger et al; licensee BioMed Central Ltd.

【 图 表 】

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