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United States Department of Agriculture

Agricultural Research Service

Research Project: FUNCTIONAL GENOMIC APPROACHES FOR CONTROLLING DISEASES OF SWINE

Location: Animal Parasitic Diseases

Title: Interferon induced IFIT family genes in host antiviral defense

Authors
item Zhou, Xiang -
item Michal, Jennifer -
item Zhang, Lifan -
item Ding, Bo -
item Lunney, Joan
item Liu, Bang -
item Jiang, Zhihua -

Submitted to: International Journal of Biological Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 23, 2013
Publication Date: February 11, 2013
Citation: Zhou, X., Michal, J.J., Zhang, L., Ding, B., Lunney, J.K., Liu, B., Jiang, Z. 2013. Interferon induced IFIT family genes in host antiviral defense. International Journal of Biological Sciences. 9:200-208.

Interpretive Summary: Understanding immune mechanisms regulating anti-pathogen immunity is essential for disease control and vaccine design. Secretion of interferons (IFNs) from virus-infected cells is a hallmark of effective host antiviral immunity. When processes are evaluated it is clear that IFNs exert their antiviral activities through the induction of numerous antiviral proteins. One family, the IFN-induced protein with tetratricopeptide repeats (IFITs) family, is among hundreds of IFN-stimulated genes. This family contains a cluster of duplicated loci; most mammals have IFIT1, IFIT2, IFIT3 and IFIT5. The IFIT family genes are predominantly induced by type I and type III interferons and are regulated by a few immune pathways, the pathogen pattern recognition pathway and the JAK-STAT signaling pathway. One mechanism for some viruses to escape the antiviral functions of the IFIT family genes is by suppressing IFIT family genes expression or methylation of its own 5' cap viral molecules. This review provides a comprehensive picture of the structure and function of IFIT family genes in response to pathogens.

Technical Abstract: Secretion of interferons (IFNs) from virus-infected cells is a hallmark of host antiviral immunity and in fact, IFNs exert their antiviral activities through the induction of antiviral proteins. The IFN-induced protein with tetratricopeptide repeats (IFITs) family is among hundreds of IF stimulated genes. This family contains a cluster of duplicated loci. Most mammals have IFIT1, IFIT2, IFIT3 and IFIT5; however, bird, marsupial, frog and fish have only IFIT5. Regardless of species, IFIT5 is always adjacent to SLC16A12. IFIT family genes are predominantly induced by type I and type III interferons and are regulated by the pattern recognition and the JAK-STAT signaling pathway. IFIT family proteins are involved in many processes in response to viral infection. However, some viruses can escape the antiviral functions of the IFIT family by suppressing IFIT family genes expression or methylation of 5' cap of viral molecules. In addition, the variants of IFIT family genes could significantly influence the outcome of hepatitis C virus (HCV) therapy. We believe that our current review provides a comprehensive picture for the community to understand the structure and function of IFIT family genes in response to pathogens in human, as well as in animals.

Last Modified: 9/20/2014