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

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 had only limited efficacy in cattle. Recently, a new family of IFNs, type III IFN or IFN-λ, has been identified in human, mouse, chicken, and swine. We have identified bovine IFN-λ3 (boIFN-λ3), also known as interleukin 28B (IL-28B), and demonstrated that expression of this molecule using a recombinant replication-defective human adenovirus type 5 (Ad5) vector, Ad5-boIFN-λ3, exhibited antiviral activity against FMDV in bovine cell culture. Furthermore, inoculation of cattle with Ad5-boIFN-λ3 induced systemic antiviral activity and upregulation of IFN-stimulated gene expression in the upper respiratory airways and skin. In the present study, we demonstrated that disease could be delayed for at least 6 days when cattle were inoculated with Ad5-boIFN-λ3 and challenged 24 h later by intradermolingual inoculation with FMDV. Furthermore, the delay in the appearance of disease was significantly prolonged when treated cattle were challenged by aerosolization of FMDV, using a method that resembles the natural route of infection. No clinical signs of FMD, viremia, or viral shedding in nasal swabs was found in the Ad5-boIFN-λ3-treated animals for at least 9 days postchallenge. Our results indicate that boIFN-λ3 plays a critical role in the innate immune response of cattle against FMDV. To this end, this work represents the most successful biotherapeutic strategy so far tested to control FMDV in cattle.

• Authors: Eva Perez-Martin, Marcelo Weiss, Fayna Diaz-San Segundo, Juan M Pacheco, Jonathan Arzt, Marvin J Grubman, Teresa de los Santos
• Journal: Journal of virology (J Virol) Vol. 86 Issue 8 Pg. 4477-87 (Apr 2012) ISSN: 1098-5514 [Electronic] United States
• PMID: 22301155 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• Antiviral Agents
• Interferon-gamma

Topics

• Animals
• Antibodies, Neutralizing (blood, immunology)
• Antibodies, Viral (blood, immunology)
• Antiviral Agents
• Cattle
• Cattle Diseases (immunology, therapy)
• Cell Line
• Cricetinae
• Foot-and-Mouth Disease (genetics, immunology, therapy)
• Foot-and-Mouth Disease Virus (immunology)
• Gene Expression Profiling
• Gene Expression Regulation
• Humans
• Interferon-gamma (genetics)
• Leukocytes, Mononuclear (metabolism)
• Treatment Outcome