Abstract
Interferon-induced proteins with tetratricopeptide repeats (IFITs) are involved in the protective response to viral infection, although the precise mechanism of IFITs for reducing viral proliferation is currently unknown. The interaction with the translation initiation factor eIF-3 or viral proteins and the sequestering of viral RNA have been proposed as potential antiviral functions for these proteins. In humans, four members of this family have been characterized. Nevertheless, information about these proteins in fish is almost non-existent. Exploiting the conservation of synteny between human and zebrafish genomes, we have identified ten members of the IFIT family located on four different chromosomes. The induction of these genes was examined both in vitro and in vivo after interferon (IFN) administration and rhabdovirus challenge. Whereas an induction of IFIT genes was observed after interferon treatments (IFNΦ1, IFNΦ2 and IFNΦ3), the viral infection did not affect these IFN-induced genes in vitro, and even reduced the IFN-induced expression of these genes. The response was largely different in vivo, with a broad up-regulation of IFIT genes after viral challenge. In addition, three selected IFITs were cloned in an expression vector and microinjected into zebrafish larvae to examine the protective effect of IFITs upon viral infection. Reduction in the mortality rate was observed confirming a conserved antiviral function in non-mammalian species.
Highlights
Host antiviral innate immune responses begin with the detection of viruses, which triggers the induction of cellular and molecular effectors with broad antiviral activities [1], including type I interferon (IFN) and hundreds of IFN-stimulated genes (ISGs), which contribute to the overall effects against a given virus [2,3].In fish, numerous IFN genes have been characterized, their classification is controversial, as these genes are more diverse than previously thought, and their genomic structures, containing introns, are reminiscent of mammalian type III interferons (IFN-l), the encoded proteins are similar to type I interferons [5]
To determine whether the trend of down-modulation of IFNinduced genes through spring viraemia of carp virus (SVCV) infection occurred in vivo, we examined Interferon-induced proteins with tetratricopeptide repeats (IFITs) genes expression in kidney cells from adult animals injected with the virus
IFITs are a novel IFN-stimulated gene family with antiviral properties not formally described in fish until a recent published work [25]
Summary
Host antiviral innate immune responses begin with the detection of viruses, which triggers the induction of cellular and molecular effectors with broad antiviral activities [1], including type I interferon (IFN) and hundreds of IFN-stimulated genes (ISGs), which contribute to the overall effects against a given virus [2,3].In fish, numerous IFN genes have been characterized (reviewed in [4]), their classification is controversial, as these genes are more diverse than previously thought, and their genomic structures, containing introns, are reminiscent of mammalian type III interferons (IFN-l), the encoded proteins are similar to type I interferons [5]. Fish type I IFNs, named as interferon-phi (IFNW) were classified in two groups: group I (comprising IFNW1 and IFNW4) and group II (composed by IFNW2 and IFNW3) [6,7]. These two groups of IFNs do not bind to the same receptor complexes in zebrafish, as was shown by Aggad et al [8]. MX is a well-studied ISG in fish but our knowledge of other ISGs (e.g., Vig-1/viperin, ISG15, finTRIMs, and PKR) in fish is limited (reviewed in [12]). The importance of the IFN system is clear, there is not enough information concerning the mechanism underlying the IFN-mediated inhibition of viral replication, in vivo [13]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
