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Title: Understanding the mechanism of interferon-induced protection against foot-and-mouth disease

Author
item Diaz San Segundo, Fayna
item MONTIEL, NESTOR - Oak Ridge Institute For Science And Education (ORISE)
item De Los Santos, Teresa
item Grubman, Marvin

Submitted to: Book Chapter
Publication Type: Book / Chapter
Publication Acceptance Date: 6/14/2013
Publication Date: 2/20/2014
Citation: Diaz San Segundo, F.C., Montiel, N., De Los Santos, T.B., Grubman, M.J. 2014. Understanding the mechanism of interferon-induced protection against foot-and-mouth disease. In: IConcept Press, Ltd. Virology II Advanced Issues. 1st edition. United States of America: IConcept Press Ltd. p. 51-72.

Interpretive Summary: Foot-and-mouth disease virus (FMDV) causes a serious disease of several livestock species, threatening global trade, food security and economic development. Current vaccines require approximately 7 days to induce protection, thus, prior to this time, vaccinated animals are still susceptible to infection. We have previously demonstrated that FMDV is highly sensitive to the action of interferons (IFN). Swine treated with type I IFN, and cattle treated with type III IFN are protected against FMD as early as 24 hours post treatment. Furthermore, it has been reported that, both type I and type III IFNs trigger similar responses upon stimulation of hundred of host genes, however a tailored response specific for each type of virus mediates an effective control of infection. In recent years we have taken a comprehensive approach to elucidate the mechanism involved in the IFN-mediated protection against FMD. In this chapter we summarize our results, including new data and reviewing the current available literature in the topic. We believe that an improved understanding of the intricate interactions between FMDV and the host response to IFN treatment will ultimately contribute to the development of improved disease control strategies.

Technical Abstract: Foot-and-mouth disease virus (FMDV) infects cloven-hoofed animals and causes a highly contagious disease that rapidly spreads among many susceptible species. Vaccination with an inactivated whole virus antigen in formulation with adjuvant, or with a replication-defective human adenovirus 5 (Ad5) able to deliver FMDV empty capsids have proven to be effective strategies to control disease in 7 days. However, in the event of an FMD outbreak, the induction of rapid protection prior to the development of vaccine-stimulated adaptive immunity is necessary to limit the spread of this disease that can cause economically devastating consequences. Similarly to many other viruses, FMDV is highly sensitive to the action of interferons (IFNs), the first line of defense against viral infection. Furthermore, IFN delivered by an Ad5 vector can protect animals from FMDV infection as early as 1 day post-administration. Initial studies in vivo have provided valuable information about the effect of IFN treatment on host gene induction and cell mediated immunity during FMDV infection. A detailed and comprehensive understanding of the mechanisms involved in IFN-induced protection should only contribute to the development of novel and improved FMD control strategies.