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Title: Bovine type III interferon significantly delays and reduces the severity of foot-and-mouth disease in cattle

Author
item PEREZ-MARTIN, EVA - Oak Ridge Institute For Science And Education (ORISE)
item WEISS, MARCELO - Oak Ridge Institute For Science And Education (ORISE)
item Diaz San Segundo, Fayna
item Pacheco Tobin, Juan
item Arzt, Jonathan
item Grubman, Marvin
item De Los Santos, Teresa

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/23/2012
Publication Date: 2/1/2012
Citation: Perez-Martin, E., Weiss, M., Diaz San Segundo, F.C., Pacheco Tobin, J., Arzt, J., Grubman, M.J., De Los Santos, T.B. 2012. Bovine type III interferon significantly delays and reduces the severity of foot-and-mouth disease in cattle. Journal of Virology. 86(8):4477-4487.

Interpretive Summary: Interferons (IFNs) are the first line of defense against viral infections. In previous work we demonstrated that type I IFN is effective to control foot-and-mouth disease virus (FMDV) infection in swine, however a similar approach only had limited success in cattle. More recently we have identified a member of the bovine type III IFN family (boIFN -lambda3) and demonstrated that cattle inoculated with a replication defective human adenovirus type 5 (Ad5) expressing boIFN -lambda3 have systemic antiviral activity and a localized induction of IFN stimulated genes in epithelial tissues that are known targets for FMDV growth. In the current study we evaluated if treatment of cattle with Ad5-boIFNlambda3 can prevent or limit FMD. We demonstrated that cattle treated with Ad5-boIFNlambda3 can be protected from disease for 6 days when challenged 24 hours post treatment by direct inoculation in the tongue with FMDV A24 Cruzeiro. Such protection was significantly improved –no disease until day 9- when treated cattle were challenged by an aerosol route with FMDV O1 Manisa. These results suggest that, in cattle, boIFNlambda3 plays a critical role in the innate immune response against infection with FMDV.

Technical Abstract: Interferons (IFNs) are the first line of defense against viral infections. Although type I and II IFNs have proven effective to inhibit foot-and-mouth disease virus (FMDV) replication in swine, a similar approach has had only limited efficacy in cattle. Recently, a new family of IFNs, type III IFN or IFNlambda, has been identified in humans, mice, chicken and swine. We have identified bovine (bo) IFNlambda3 and demonstrated that expression of this IFN using a recombinant replication-defective human adenovirus type 5 (Ad5) vector, Ad5-boIFNlambda3, exhibited antiviral activity against FMDV in bovine cell culture. Furthermore, inoculation of cattle with Ad5-boIFNlambda3 induced systemic antiviral activity and up-regulation of IFN stimulated gene (ISG) expression in tissues susceptible to FMDV infection including the upper respiratory airways and skin. In the present study we demonstrated that cattle treated with Ad5-boIFNlambda3 can be protected from disease for 6 days when challenged 24 hours post treatment by intradermal inoculation in the tongue with FMDV A24 Cruzeiro. Such protection was significantly improved when treated cattle were challenged by an aerosol route with FMDV O1 Manisa. No clinical signs of FMD, viremia or viral shedding in nasal swabs were found in the Ad5-boIFNlambda3 treated animals for at least 9 days post FMDV challenge. These results suggest that, as previously reported in other species, boIFNlambda3 plays a critical role in the innate immune response of cattle against infection with FMDV.