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Title: Antiviral activity of bovine type III interferon against foot-and-mouth disease virus

Author
item DIAZ-SAN SEGUNDO, FAYNA - Oak Ridge Institute For Science And Education (ORISE)
item WEISS, MARCELO - Oak Ridge Institute For Science And Education (ORISE)
item PEREZ-MARTIN, EVA - Oak Ridge Institute For Science And Education (ORISE)
item Koster, Marla
item Zhu, James
item Grubman, Marvin
item De Los Santos, Teresa

Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/26/2011
Publication Date: 5/10/2011
Citation: Diaz-San Segundo, F., Weiss, M., Perez-Martin, E., Koster, M.J., Zhu, J.J., Grubman, M.J., De Los Santos, T.B. 2011. Antiviral activity of bovine type III interferon against foot-and-mouth disease virus. Virology. 413(2):283-292.

Interpretive Summary: Interferons are the first line of defense against viral infections and administration of interferons as biotherapeutics has been demonstrated to be effective in controlling several viral infections. Here we report for the first time the identification and characterization of a member of the bovine type III IFN family, boIFN-lambda3, also named interleukin (IL) 28B. We have cloned and expressed boIFN-lambda3 using a recombinant replication defective human adenovirus type 5 (Ad5). We demonstrated that the identified boIFN-lambda3 has antiviral activity against foot-and-mouth disease virus (FMDV) and vesicular stomatitis virus (VSV) in bovine cells. Furthermore we showed that inoculation of cattle with Ad5-boIFN-lambda3 induces a systemic antiviral state and up-regulates the expression of IFN stimulated genes with antiviral properties in mucosal tissues of the upper airways and in the skin, tissues that are the primary and preferred sites of FMDV replication. These results indicate that the identified boIFN-lambda3 deserves future attention in efficacy studies against FMDV and potentially could be evaluated in controlling other bovine viral diseases that affect mucosal tissues or skin.

Technical Abstract: Interferons (IFN) are the first line of defense against viral infections. Recently a new family of IFNs, type III, has been identified in humans, mice, swine and chickens. Here we report the identification and characterization of a member of the bovine type III IFN family, boIFN-lambda3, also known as interleukin (IL) 28B. Expression of boIFN-lambda3 using a recombinant replication-defective human adenovirus type 5 (Ad5) vector resulted in a secreted protein of about 21.5 kDa that exhibited antiviral activity against foot-and-mouth disease virus (FMDV) and vesicular stomatitis virus in cell culture. Inoculation of cattle with Ad5-boIFN-lambda3 induced systemic antiviral activity and up-regulation of IFN stimulated gene (ISG) expression in tissues susceptible to FMDV infection. Our results demonstrate that the type III IFN family is conserved in bovines and that boIFN-lambda3 has potential for further development as a biotherapeutic candidate to inhibit FMDV or other viral infections in cattle.