Grouper IFIT1 inhibits iridovirus and nodavirus infection by positively regulating interferon response

Ya Zhang; Yuxin Wang; Zetian Liu; Jiaying Zheng; Youhua Huang; Xiaohong Huang; Qiwei Qin

doi:10.1016/j.fsi.2019.08.075

Grouper IFIT1 inhibits iridovirus and nodavirus infection by positively regulating interferon response

Fish Shellfish Immunol. 2019 Nov:94:81-89. doi: 10.1016/j.fsi.2019.08.075. Epub 2019 Aug 30.

Authors

Ya Zhang¹, Yuxin Wang¹, Zetian Liu¹, Jiaying Zheng¹, Youhua Huang¹, Xiaohong Huang², Qiwei Qin³

Affiliations

¹ College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China.
² College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China. Electronic address: huangxh@scau.edu.cn.
³ College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266000, PR China. Electronic address: qinqw@scau.edu.cn.

PMID: 31476389
DOI: 10.1016/j.fsi.2019.08.075

Abstract

Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), one of the interferon stimulated genes (ISGs), is strongly induced by type I interferon (IFN), double-stranded RNAs and virus infection. To investigate the actions of fish IFIT1 in response to virus infection, we cloned an IFIT1 homolog from orange spotted grouper (EcIFIT1) and clarified its function in this study. The full-length cDNA of EcIFIT1 is 1839 bp, which is composed of 436 amino acid (aa) residues, with 77.8% and 22.8% identity to IFIT1 homolog of yellow perch (Perca flavescens) and humans (homo sapiens), respectively. Sequence alignment analysis showed that EcIFIT1 contained three tetratricopeptide repeats (TPRs). Tissue distribution analysis indicated that EcIFIT1 was abundant in intestine, spleen, liver, and heart. Moreover, EcIFIT1 was significantly up-regulated by Singapore grouper iridovirus (SGIV) or red-spotted grouper nervous necrosis virus (RGNNV) infection, and polyinosinic-polycytidylic acid (poly I:C) or lipopolysaccharide (LPS) treatment in vitro. Under fluorescence microscopy, EcIFIT1 was found to localize throughout the cytoplasm in transfected cells. EcIFIT1 overexpression significantly suppressed the replication of SGIV and RGNNV, demonstrated by decreasing the cytopathic effect (CPE) severity, viral gene transcription and the virus titers. Further studies showed that the ectopic expression of EcIFIT1 increased the transcription level of IFN related molecules, including IFN regulatory factor (IRF) 3, IRF7, IFN stimulated gene (ISG) 15 and myxovirus resistance gene (MX) I. Meanwhile, the expression levels of pro-inflammation cytokines were differently regulated by the ectopic expression of EcIFIT1. In addition, flow cytometry analysis suggested that EcIFIT1 overexpression affected cell cycle progression by mediating S/G2 transition. Taken together, our results indicated that EcIFIT1 might exert antiviral function against fish virus by up-regulating interferon response or affecting cell cycle.

Keywords: Grouper; IFIT1; Interferon; RGNNV; SGIV.

MeSH terms

Amino Acid Sequence
Animals
Bass / genetics*
Bass / immunology*
Carrier Proteins / chemistry
Carrier Proteins / genetics*
Carrier Proteins / immunology*
DNA Virus Infections / immunology
DNA Virus Infections / veterinary
Fish Diseases / immunology*
Fish Proteins / chemistry
Fish Proteins / genetics
Fish Proteins / immunology
Gene Expression Profiling / veterinary
Gene Expression Regulation / immunology*
Immunity, Innate / genetics*
Lipopolysaccharides / pharmacology
Nodaviridae / physiology
Phylogeny
Poly I-C / pharmacology
RNA Virus Infections / immunology
RNA Virus Infections / veterinary
Ranavirus / physiology
Sequence Alignment / veterinary

Substances

Carrier Proteins
Fish Proteins
Lipopolysaccharides
Poly I-C