Submitted to: Clinical and Vaccine Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 3, 2010
Publication Date: May 1, 2010
Citation: Miller, L.C., Zanella, E.L., Waters, W.R., Lager, K.M. 2010. Cytokine Protein Expression Levels in Tracheobronchial Lymph Node Homogenates of Pigs Infected with Pseudorabies Virus. Clinical and Vaccine Immunology. 17(5):728-734. Interpretive Summary: Pseudorabies virus (PRV) can infect swine causing severe pneumonia and inflammation of the brain that is frequently fatal in young pigs. This virus was eradicated about 6 years ago from domestic swine in the United States as part of the USDA Veterinary Services PRV Eradication Program. However, feral swine can still be infected with PRV and the continued expansion of the feral swine population in North America presents an increasing threat to the PRV-free status of the US commercial swine herd. Reducing this threat requires a multi-pronged attack. One area of study involves understanding potential differences between domestic and feral swine PRV strains with the goal of using this knowledge to prevent infection of domestic swine with feral swine viruses. Although previous studies support different routes of transmission for domestic and feral swine PRV strains (respiratory vs. venereal), the mechanism for such a difference is not known. This paper reports the initial work establishing the effect a feral swine PRV isolate had in domestic swine at the molecular level. It will lay the groundwork for future comparative studies between domestic and feral swine PRV strains as well as other swine viruses. This line of research will provide insight into how PRV affects the swine immune system and will contribute to a better understanding of how this virus might transmit from feral domestic swine.
Technical Abstract: Pseudorabies virus (PRV) is a neurotropic alphaherpesvirus that produces fatal encephalitis in newborn pigs, respiratory disorders in fattening pigs and reproductive failure in sows. Following primary infection of the respiratory tract, PRV can develop into a systemic infection with dispersion of the virus via the lymphatic system that involves mononuclear cells in tracheobronchial lymph nodes (TBLN). The objectives of this study were to evaluate the pathogenesis and determine early immune cytokine profiles in TBLN following experimental infection with a feral swine PRV isolate at 1, 3, 6 and 14 days post-infection (dpi). Forty conventionally raised 4-5 week old pigs, free of clinical disease, were purchased from a PRV-negative herd. Twenty pigs received the Florida strain isolate (FS 268) of feral swine PRV intranasally and 20 uninfected controls received a sham inoculum. As compared to controls, interferon (IFN) -alpha, interleukin (IL) -1beta, IL-12, and IFN-gamma were increased in TBLN homogenates from PRV-infected pigs at 1 dpi whereas IL-18 was decreased from 3 to 6 dpi. Protein levels of IL-4 and IL-10 did not differ between controls and PRV-infected pigs at any time points. Flow cytometric analysis of TBLN homogenates revealed increases in B cell percentages at 6 dpi and CD4+ cells at 14 dpi in PRV-infected pigs versus controls. CD25 expression was increased in TBLN homogenates (total mononuclear fraction and on B cells) at 14 dpi in PRV-infected pigs versus controls. Collectively, these findings demonstrate in commercial swine that a feral PRV can modulate the host’s early immune response that can allow the virus to establish an infection.