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Studies on the cellular and molecular mechanisms of innate host susceptibility and resistance to influenza A viruses in chicken and ducks

Kuchipudi, Suresh Varma (2010) Studies on the cellular and molecular mechanisms of innate host susceptibility and resistance to influenza A viruses in chicken and ducks. PhD thesis, University of Glasgow.

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Abstract

Avian influenza viruses are considered to be key contributors to the emergence of human influenza pandemics. While aquatic birds and ducks are the major reservoir for influenza viruses, they are typically resistant to the effects of viral infection, in contrast to the frequently severe disease observed in chickens. In order to understand whether differences in receptors might contribute to this observation, anatomical distribution of influenza virus receptors (sialic acid SAα2,3-Gal and SA α2,6-Gal) in key organs of both species was studied using lectin histochemistry with linkage specific lectins, and receptor binding assays with swine H1N1 (classical A/sw/Iowa/15/30) and avian H2N3 (A/mallard duck/England/7277/06) influenza viruses. Widespread presence of both SAα 2,6-Gal and SAα2,3-Gal receptors were found in all major organs examined in both chickens and ducks. Interestingly, the predominant receptor type in chicken tracheal epithelium (TE) was SAα2,6-Gal whereas SAα2,3-Gal receptors were most abundant in duck TE. Paradoxically, infection of primary cell cultures (duck and chicken lung cells and embryo fibroblasts) with the swine H1N1, the low pathogenicity avian H2N3, and a highly pathogenic H5N1 (A/turkey/England/50-92/91) virus resulted in more extensive and rapid cell death in duck cells than in chicken cells. Infected duck cells displayed morphological features of apoptosis, increased DNA fragmentation and activation of caspase-3/7. Infected duck cells produced comparable levels of viral RNA but less infectious virus than infected chicken cells. Notably, such rapid cell death was not observed in duck cells infected with a contemporary Eurasian lineage H5N1 virus (A/turkey/Turkey/1/05) which has been shown to be fatal to ducks. Gene expression profiling of infected chicken and duck cells, 24hrs post-infection, with a chicken Affymetrix microarray platform revealed differential transcription of many genes between the two avian species. In particular, the array results suggested a possible role of BCoR, HSPA-9, STAT-3, AVEN, BCLAF1, IL-18, IFN-α, and TNF-α genes in mediating the contrasting species phenotypic response to influenza infections. In summary, rapid cell death in duck cells, mediated at least in part by apoptosis, results in reduced infective virus production and may well be an important protective host response of resistant ducks. By contrast, longer surviving infected chicken cells produce much higher infective virus load along with high levels of pro-inflammatory cytokines which could account for the susceptibility of chickens to influenza infections.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Avian influenza,H5N1, innate host susceptibility and resistance, chicken, ducks
Subjects: Q Science > QR Microbiology > QR180 Immunology
S Agriculture > SF Animal culture > SF600 Veterinary Medicine
Q Science > QR Microbiology > QR355 Virology
Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
Supervisor's Name: Dunham, Dr. Stephen P and Chang, Prof. Kin Chow
Date of Award: 2010
Depositing User: Dr Suresh Varma Kuchipudi
Unique ID: glathesis:2010-2167
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 11 Oct 2010
Last Modified: 11 Oct 2013 08:42
URI: http://theses.gla.ac.uk/id/eprint/2167

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