IFIT5 potentiates anti-viral response through enhancing innate immune signaling pathways.
Humans have a distinct combination of IFIT (IFN-induced protein with tetratricopeptide repeats) family orthologs, including IFIT1 (ISG56), IFIT2 (ISG54), IFIT3 (ISG60), and IFIT5 (ISG58). The function of IFIT1/IFIT2/IFIT3 has been intensively investigated. However, little is known about the role of IFIT5 in any cellular processes. In this study, we reported that both the mRNA and protein levels of IFIT5 are up-regulated in response to RNA virus infection or polyinosinic-cytidylic acid stimulation. Ectopic expression of IFIT5 could synergize IRF3- and NF-κB-mediated gene expression, whereas knockdown of IFIT5 impairs the transcription of these genes. Consistently, anti-viral responses of host cells are significantly increased or decreased in the presence or absence of IFIT5. Mechanistically, IFIT5 co-localizes partly with mitochondria and interacts with RIG-I and MAVS. Our study identified that IFIT5 is an important enhancer in innate immune response.
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai 200241, China.
Bianhong
B
Zhang
Xinyi
X
Liu
Wei
W
Chen
Liang
L
Chen
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D050838:Interferon Regulatory Factor-3 / Q000096:biosynthesis; D016899:Interferon-beta / Q000096:biosynthesis / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000502:physiology*; D011070:Poly I-C / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011971:Receptors, Immunologic; D010253:Respirovirus Infections / Q000276:immunology*; D029082:Sendai virus; D015398:Signal Transduction / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; C110985:IFIT5 protein, human; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; C505371:MAVS protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D016899:Interferon-beta; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D011070:Poly I-C
IFIT5; IRF3; NF-κB; innate immune response