Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/2/2009
Publication Date: 10/1/2009
Citation: Abdul-Careem, M.F., Haq, K., Shanmuganthan, S., Read, L., Schat, K.A., Heidari, M., Sharif, S. 2009. Induction of Innate Host Responses in the Lungs of Chickens Following Infection With A Very Virulent Strain of Marek's Disease Virus. Virology. 393(2):250-257. Interpretive Summary: Marek’s disease (MD) causes enormous economical losses to the poultry industry. MD virus (MDV), the etiological agent of MD, is transmitted to other chickens through the respiratory route. Not knowing the time of infection and lack of an inoculation system to mimic the natural route of infection has made it difficult to investigate the induction of host immune responses in the lungs of infected chickens. The objective of this study was to examine the virus replication and innate immune responses in the lungs of chickens inoculated with an in-house built aerosol inoculation system that exposes chickens to MDV at a synchronized timing and dosing manner. Data indicates that virus genome was detectible in the lungs of inoculated chickens as early as 12 hours post exposure. The expression of Toll-like receptor (TLR)-3 and TLR-7 (components of innate immune responses) was increased in response to MDV infection when compared to age-matched control birds. In addition, there was an increase in the expression levels of other immune response components including interleukin (IL)-1beta, IL-8, and inducible nitric oxide synthase (INOS). INOS is an enzyme that catalyzes the production of nitric oxide, which has a direct inhibitory effect on MDV replication. The macrophage infiltration in the lungs of infected chickens was significantly higher when compared to the uninfected control birds. This work is significant in setting groundwork for future investigation to elucidate innate and adaptive immune responses in the lungs of MDV-infected chickens. The outcome of such studies will lead to the development of effective antiviral immunomodulatory efforts to control replication of MDV and its dissemination into the environment.
Technical Abstract: The natural route of entry of Marek’s disease virus (MDV) is via the respiratory system. However, induction of host responses in the respiratory system of chickens following inhalation of the virus has not been studied previously. The objective of the study was to examine MDV replication and induction of innate host responses in the lungs of chickens infected through inhalation. Replication of MDV and accumulation of viral genome in the lungs was detectable as early as 12 hours post-infection (hpi). The expression of Toll like receptor (TLR)3 and TLR7 genes was enhanced in response to MDV infection in the lungs. This was associated with up-regulation of interleukin (IL)-1beta and IL-8 genes. In response to MDV infection, the number of macrophages in the lungs was significantly higher compared to the lungs of uninfected control chickens. The expression level of inducible nitric oxide synthase (iNOS) gene was also significantly higher in the lungs transiently following MDV infection. Irrespective of the induction of significant innate host responses, MDV replication and genome accumulation showed a significant increase in the lungs towards the end of the study, 168 hpi. Further studies should be directed to characterize the adaptive immune responses generated in the lungs following MDV infection.