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

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

Abstract

© 2014 Kuchipudi et al.; licensee BioMed Central Ltd. 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.

Citation

Kuchipudi, S. V., Tellabati, M., Sebastian, S., Londt, B. Z., Jansen, C., Vervelde, L., Brookes, S. M., Brown, I. H., Dunham, S. P., & Chang, K.-C. (2014). Highly pathogenic avian influenza virus infection in chickens but not ducks is associated with elevated host immune and pro-inflammatory responses. Veterinary Research, 45(1), Article 118. https://doi.org/10.1186/s13567-014-0118-3

• Journal Article Type: Article
• Acceptance Date: Oct 31, 2014
• Online Publication Date: Nov 28, 2014
• Publication Date: Nov 28, 2014
• Deposit Date: Jul 5, 2017
• Publicly Available Date: Jul 5, 2017
• Journal: Veterinary Research
• Print ISSN: 0928-4249
• Electronic ISSN: 1297-9716
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 45
• Issue: 1
• Article Number: 118
• DOI: https://doi.org/10.1186/s13567-014-0118-3
• Keywords: Influenza virus, H5N1 virus, Highly pathogenic avian influenza, Influenza virus infection, Highly pathogenic avian influenza virus
• Public URL: https://nottingham-repository.worktribe.com/output/739135
• Publisher URL: https://veterinaryresearch.biomedcentral.com/articles/10.1186/s13567-014-0118-3
• Contract Date: Jul 5, 2017