Molecular immunophenotyping of lungs and spleens in naive and vaccinated chickens early after pulmonary avian influenza A (H9N2) virus infection

Abstract

In a respiratory-infection-model with the avian influenza A H9N2 virus we studied lung and splenic immune reactions in chickens using a recently developed 5K chicken immuno-microarray. Groups of chickens were either mock-immunized (referred to as non-immune), vaccinated with inactivated viral antigen only (immune) or with viral antigen in a water-in-oil (W/O) immunopotentiator (immune potentiated). Three weeks after vaccination all animals were given a respiratory infection. Immune potentiated birds developed inhibitory antiviral antibodies, showed minimal lung histopathology and no detectable viral sequences, while non-immune animals showed microscopic immunopathology and detectable virus. Immune birds, receiving antigen in saline only, showed minimal microscopic histopathology, and intermediate levels of virus detection. These classical features in the different groups were mirrored by overlapping or specific mRNA gene expression profiles in lungs and spleen using microarray analysis. To our knowledge this is the first study demonstrating pneumonia-associated lung pathology of the low pathogenic avian influenza H9N2 virus. Our data provide insights into the molecular interaction of this virus with its natural host when naive or primed by vaccination.

A Genetically Engineered Waterfowl Influenza Virus with a Deletion in the Stalk of the Neuraminidase Has Increased Virulence for Chickens

“…Our results suggest that the avian IL-6 could play a similar role in birds. They are in agreement with data from others who observed a marked increase of IL-6 mRNAs in the tracheae and lungs of chickens inoculated with a low-pathogenicity H9N2 (15,55) or H11N9 (1) influenza virus. A significant increase of TGF-␤ activity in mice (7,16) or in chickens (64) infected with high-pathogenicity influenza viruses was previously reported.…”

Chicken interferon alpha pretreatment reduces virus replication of pandemic H1N1 and H5N9 avian influenza viruses in lung cell cultures from different avian species

“…Our results with low pathogenic AI suggests that a suboptimal cytokine response maybe in part explain how H1N1 could escape the innate immune defense by impeding cytokine response. This phenomenon maybe characteristic of low pathogenic AI viruses as well since they also have demonstrated the ability to limit the host's antiviral Mx response in chickens in vivo [38]. Data presented here will contribute to a better understanding of the avian host response to the low pathogenic AI viruses, and our model of testing primary avian lung cell cultures will be useful for monitoring new AIV isolates for changes in innate immune modulation.…”

Use of Functional Genomics to Understand Influenza–Host Interactions

“…As we have described, functional genomics has been utilized to study influenza infection in a variety of model systems including cell culture, mice, and macaques. Researchers are also utilizing functional genomics to study influenza infections in chickens, but these endeavors are still in their infancy (Degen et al, 2006). It will also be desirable to use functional genomics to examine influenza infection in ferrets.…”

“…Because of its ability to provide a global view, functional genomics is one of the most useful approaches for studying virus-host interactions. Our laboratory is using functional genomics to study a variety of viruses, including HCV, SIV/HIV, Ebola virus, HSV, SARS coronavirus, West Nile virus, and influenza virus (Baas et al, 2006a,b;Baskin et al, 2004;Fredericksen et al, 2004;Geiss et al, 2000Geiss et al, , 2001Geiss et al, , 2002Geiss et al, , 2003Kash et al, 2004Kash et al, , 2006aKobasa et al, 2007;Lederer et al, 2006;Pasieka et al, 2006;Smith et al, 2003aSmith et al, ,b, 2006Thomas et al, 2006;Walters et al, 2006Walters et al, , 2006a. This chapter will focus on how microarray technology is being utilized to uncover the mysteries of influenza pathogenesis.…”