Limits...
Interferon induced IFIT family genes in host antiviral defense.

Zhou X, Michal JJ, Zhang L, Ding B, Lunney JK, Liu B, Jiang Z - Int. J. Biol. Sci. (2013)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Animal Sciences, Washington State University, Pullman, WA 99164-6351, USA.

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 IFN-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.

Show MeSH

Related in: MedlinePlus

Signaling pathway of IFIT family genes. Toll-like receptors (TLRs) and RIG-like receptors (RLRs) are pattern recognition receptors (PRRs) families that recognize pathogen-associated molecular patterns (PAMPs) that trigger signaling. TLR3 and RIG-I sense dsRNA, while TLR4 senses LPS, TLR7/8 senses ssRNA and TLR9 senses CpG DNA. Adapter proteins MYD88, TRIF and ISP-1 are used by the receptor complex that activate IRF3 and IRF7 by phosphorylaton, which then bind the DNA to stimulate IFN expression. Secreted IFN binds the receptor IFNAR at the cell surface, followed by activation of STAT1 and STAT2. The phosphorylated STAT1, STAT2, and IRF9 form the ISGF3 complex, which is translocated into the nucleus, binds with the ISRE elements in the promoter of IFIT family genes, and thus stimulates IFIT family genes expression.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3584916&req=5

Figure 3: Signaling pathway of IFIT family genes. Toll-like receptors (TLRs) and RIG-like receptors (RLRs) are pattern recognition receptors (PRRs) families that recognize pathogen-associated molecular patterns (PAMPs) that trigger signaling. TLR3 and RIG-I sense dsRNA, while TLR4 senses LPS, TLR7/8 senses ssRNA and TLR9 senses CpG DNA. Adapter proteins MYD88, TRIF and ISP-1 are used by the receptor complex that activate IRF3 and IRF7 by phosphorylaton, which then bind the DNA to stimulate IFN expression. Secreted IFN binds the receptor IFNAR at the cell surface, followed by activation of STAT1 and STAT2. The phosphorylated STAT1, STAT2, and IRF9 form the ISGF3 complex, which is translocated into the nucleus, binds with the ISRE elements in the promoter of IFIT family genes, and thus stimulates IFIT family genes expression.

Mentions: IFIT family gene expression relies on pattern recognition and the JAK-STAT pathway. Pathogen-associated molecular patterns (PAMPs) are molecules associated with groups of pathogens including viruses, bacteria, fungi and others. Pattern recognition receptors (PRRs) recognize different PAMPs during pathogen infection and activate downstream signaling molecules 29. As a result, Toll-like receptors (TLRs) signaling and RIG-like receptors (RLRs) signaling induce IFIT family gene expression 30. TLR3 senses double-stranded RNA (dsRNA), TLR7 and TLR8 sense single-stranded RNA (ssRNA), and TLR9 recognizes CpG-DNA 31. The TIR domain-containing adaptor inducing IFN-β (TRIF)-dependent signaling pathway or myeloid differentiation primary response gene (88) (MyD88)-dependent signaling pathway transfect the signal from the TLRs, which leads to the activation of IRF3 or IRF7 by phosphorylation. The activated IRF3 or IRF7 is then translocated to the nucleus, resulting in type I interferon gene expression (Figure 3) 32. For example, irf3(-/-) mice lack expression of type I interferon and IFIT family genes in macrophages and cortical neurons during WNV infection 33. In addition, secretory IFNs bind to IFN receptors at the cell surface, which then activate Janus kinase (JAK) and signal transducers and activators of transcription (STAT) pathways. The phosphorylated STAT1, STAT2, and IRF9 form the ISGF3 complex that translocates into the nucleus and binds to the ISRE elements in the promoter of IFIT family genes, thus stimulating IFIT family genes expression (Figure 3) 34. RIG-I-like receptors (RLRs) are located in the cytoplasm and recognize dsRNA that originated from the genomic RNA of dsRNA viruses or is generated during replication of ssRNA viruses 35. The adaptor IFN-β-promoter stimulator 1 (IPS-1) located in mitochondria interacts with the caspase-recruitment domain (CARDs) of RLRs and triggers signaling cascades and enhances IFN expression, thus stimulating IFIT family gene expression though JAK-STAT signaling as a result of TLRs signaling (Figure 3) 36 .


Interferon induced IFIT family genes in host antiviral defense.

Zhou X, Michal JJ, Zhang L, Ding B, Lunney JK, Liu B, Jiang Z - Int. J. Biol. Sci. (2013)

Signaling pathway of IFIT family genes. Toll-like receptors (TLRs) and RIG-like receptors (RLRs) are pattern recognition receptors (PRRs) families that recognize pathogen-associated molecular patterns (PAMPs) that trigger signaling. TLR3 and RIG-I sense dsRNA, while TLR4 senses LPS, TLR7/8 senses ssRNA and TLR9 senses CpG DNA. Adapter proteins MYD88, TRIF and ISP-1 are used by the receptor complex that activate IRF3 and IRF7 by phosphorylaton, which then bind the DNA to stimulate IFN expression. Secreted IFN binds the receptor IFNAR at the cell surface, followed by activation of STAT1 and STAT2. The phosphorylated STAT1, STAT2, and IRF9 form the ISGF3 complex, which is translocated into the nucleus, binds with the ISRE elements in the promoter of IFIT family genes, and thus stimulates IFIT family genes expression.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3584916&req=5

Figure 3: Signaling pathway of IFIT family genes. Toll-like receptors (TLRs) and RIG-like receptors (RLRs) are pattern recognition receptors (PRRs) families that recognize pathogen-associated molecular patterns (PAMPs) that trigger signaling. TLR3 and RIG-I sense dsRNA, while TLR4 senses LPS, TLR7/8 senses ssRNA and TLR9 senses CpG DNA. Adapter proteins MYD88, TRIF and ISP-1 are used by the receptor complex that activate IRF3 and IRF7 by phosphorylaton, which then bind the DNA to stimulate IFN expression. Secreted IFN binds the receptor IFNAR at the cell surface, followed by activation of STAT1 and STAT2. The phosphorylated STAT1, STAT2, and IRF9 form the ISGF3 complex, which is translocated into the nucleus, binds with the ISRE elements in the promoter of IFIT family genes, and thus stimulates IFIT family genes expression.
Mentions: IFIT family gene expression relies on pattern recognition and the JAK-STAT pathway. Pathogen-associated molecular patterns (PAMPs) are molecules associated with groups of pathogens including viruses, bacteria, fungi and others. Pattern recognition receptors (PRRs) recognize different PAMPs during pathogen infection and activate downstream signaling molecules 29. As a result, Toll-like receptors (TLRs) signaling and RIG-like receptors (RLRs) signaling induce IFIT family gene expression 30. TLR3 senses double-stranded RNA (dsRNA), TLR7 and TLR8 sense single-stranded RNA (ssRNA), and TLR9 recognizes CpG-DNA 31. The TIR domain-containing adaptor inducing IFN-β (TRIF)-dependent signaling pathway or myeloid differentiation primary response gene (88) (MyD88)-dependent signaling pathway transfect the signal from the TLRs, which leads to the activation of IRF3 or IRF7 by phosphorylation. The activated IRF3 or IRF7 is then translocated to the nucleus, resulting in type I interferon gene expression (Figure 3) 32. For example, irf3(-/-) mice lack expression of type I interferon and IFIT family genes in macrophages and cortical neurons during WNV infection 33. In addition, secretory IFNs bind to IFN receptors at the cell surface, which then activate Janus kinase (JAK) and signal transducers and activators of transcription (STAT) pathways. The phosphorylated STAT1, STAT2, and IRF9 form the ISGF3 complex that translocates into the nucleus and binds to the ISRE elements in the promoter of IFIT family genes, thus stimulating IFIT family genes expression (Figure 3) 34. RIG-I-like receptors (RLRs) are located in the cytoplasm and recognize dsRNA that originated from the genomic RNA of dsRNA viruses or is generated during replication of ssRNA viruses 35. The adaptor IFN-β-promoter stimulator 1 (IPS-1) located in mitochondria interacts with the caspase-recruitment domain (CARDs) of RLRs and triggers signaling cascades and enhances IFN expression, thus stimulating IFIT family gene expression though JAK-STAT signaling as a result of TLRs signaling (Figure 3) 36 .

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Animal Sciences, Washington State University, Pullman, WA 99164-6351, USA.

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 IFN-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.

Show MeSH
Related in: MedlinePlus