CHARACTERIZATION OF PROTECTIVE HOST RESPONSES TO AVIAN INFLUENZA VIRUS INFECTIONS IN AVIAN SPECIES
Location: Exotic and Emerging Avian Viral Diseases Research Unit
Title: Use of interferon treatment to protect chickens against highly pathogenic avian influenza
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: July 15, 2012
Publication Date: September 25, 2012
Citation: Kapczynski, D.R., Zsak, A., Ewald, S., Suarez, D.L. 2012. Use of interferon treatment to protect chickens against highly pathogenic avian influenza [abstract]. International Symposium on Alternatives to Antibiotics in Animal Production Meeting. CDROM.
Avian influenza (AI) is a significant public health concern and serious economic threat to the commercial poultry industry worldwide. While properly matched vaccines can be effective at limiting morbidity and mortality, the use of therapeutics in veterinary animals to combat this disease are relatively non-existent. Interferons (IFNs) are a group of polypeptides that are secreted from most all eukaryotic cells in response to external signals. They are classified into three groups, designated type I, type II and type III. Type I IFN (alpha and beta), are expressed rapidly after viral infection, and represent a first line of defense initiated by the innate immune response. Induction of IFN-alpha results in an antiviral state which can decrease morbidity and mortality following viral infection. Immediately following infection with AI, host cells begin to express proinflammatory cytokines, including interleukin (IL)-1beta and IL-6, and Type I IFN genes, which results in a general antiviral response through the activation of a broad range of effector molecules, including Myxovirus (Mx) resistance gene 1, RNA-activated protein kinase and 2’,5’-oligoadenylate synthetases. Unlike mammals, chickens have a single Mx gene with multiple alleles. The original evaluation of chicken Mx indicated the encoded protein lacked antiviral activity; however, more recent reports have determined that the chicken Mx1 gene is highly polymorphic, and cDNAs of some but not all Mx1 alleles transfected into mouse 3T3 cells conferred protection against highly pathogenic avian influenza (HPAI) in vitro. According to that report, chicken Mx1 variants encoding Asn at position 631 have antiviral activity, whereas variants with Ser at 631 lack activity. We have previously demonstrated the protective potential of IFN-alpha applied to poultry against low pathogenic avian influenza viruses. In those studies, intranasal application of IFN-alpha during infection reduced clinical signs of disease and the incidence of viral shedding. In the present studies, we evaluated protection of chickens against HPAI in birds with different Mx during IFN-alpha application. We observed >90 percent protection from mortality that was dependent on Mx-631 allele. Birds with the Mx-Asn631 (White Leghorn) were resistant to disease whereas Mx-Ser631 birds (White Rock) were susceptible to HPAIV. Taken together, these studies show that IFN-alpha can protect chickens from disease associated with HPAIV and that the Mx-631 allele may contribute to that protection.