Highly pathogenic avian influenza virus infection in chickens but not ducks is associated with elevated host immune and pro-inflammatory responses.

Suresh V Kuchipudi,Kin-Chow Chang,Sujith Sebastian,Lonneke Vervelde,Brandon Z Londt,Christine Jansen,Stephen P Dunham,Meenu Tellabati,Sharon M Brookes,Ian H Brown

doi:10.1186/s13567-014-0118-3

Abstract

Highly pathogenic avian influenza (HPAI) H5N1 viruses cause severe infection in chickens at near complete mortality, but corresponding infection in ducks is typically mild or asymptomatic. To understand the underlying molecular differences in host response, primary chicken and duck lung cells, infected with two HPAI H5N1 viruses and a low pathogenicity avian influenza (LPAI) H2N3 virus, were subjected to RNA expression profiling. Chicken cells but not duck cells showed highly elevated immune and pro-inflammatory responses following HPAI virus infection. HPAI H5N1 virus challenge studies in chickens and ducks corroborated the in vitro findings. To try to determine the underlying mechanisms, we investigated the role of signal transducer and activator of transcription-3 (STAT-3) in mediating pro-inflammatory response to HPAIV infection in chicken and duck cells. We found that STAT-3 expression was down-regulated in chickens but was up-regulated or unaffected in ducks in vitro and in vivo following H5N1 virus infection. Low basal STAT-3 expression in chicken cells was completely inhibited by H5N1 virus infection. By contrast, constitutively active STAT-3 detected in duck cells was unaffected by H5N1 virus infection. Transient constitutively-active STAT-3 transfection in chicken cells significantly reduced pro-inflammatory response to H5N1 virus infection; on the other hand, chemical inhibition of STAT-3 activation in duck cells increased pro-inflammatory gene expression following H5N1 virus infection. Collectively, we propose that elevated pro-inflammatory response in chickens is a major pathogenicity factor of HPAI H5N1 virus infection, mediated in part by the inhibition of STAT-3.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-014-0118-3) contains supplementary material, which is available to authorized users.

Highlights

Avian influenza A viruses continue to spread globally causing millions of poultry deaths and are significant zoonotic pathogens [1]
Comparable susceptibility to influenza virus infection and viral RNA accumulation in chicken and duck cells Infection of primary chicken and duck lung cells with low pathogenicity avian influenza (LPAI)-H2N3, H5N1-tyEng91 or H5N1-tyTR05 at 1.0 multiplicity of infection (MOI) based on MDCK cell titration resulted in comparable levels of virus infection as determined by virus NP detection by immunocytochemistry at 6 hpi (Figure 1A to H)
More immune-related genes in chicken cells than duck cells were induced by influenza virus infection A DNA microarray based global gene expression approach with a chicken GeneChip array (Affymetrix) was used to identify differences in gene expression between chicken and duck primary lung cells in response to 24 h of infection with LPAI H2N3, H5N1-tyEng91 or H5N1-tyTR05 viruses

Summary

Introduction

Avian influenza A viruses continue to spread globally causing millions of poultry deaths and are significant zoonotic pathogens [1]. Eurasian lineage highly pathogenic avian influenza (HPAI) H5N1 virus infection causes severe disease in humans with a fatality rate of about 60% [2]. Most HPAI H5N1 virus strains produce very severe disease in chickens, turkeys and quails often causing up to 100% mortality within 2–3 days [7,8]. With their natural resistance, ducks support genetic reassortment of influenza viruses providing a mechanism of evolution of genetically diverse IAVs including HPAI H5N1 viruses [9,10,11].

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