Infection and microbial molecular motifs modulate transcription of the interferon-inducible gene ifit5 in a teleost fish

Bela-Ong, Dennis; Greiner-Tollersrud, Linn; Wal, Yorick Andreas van der; Jensen, Ingvill; Seternes, Ole Morten; Jørgensen, Jorunn B.

doi:10.1016/j.dci.2020.103746

Cited by 5 publications

(4 citation statements)

References 86 publications

(92 reference statements)

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“…FerritVac NPs upregulated the ifit5 gene at all incubated doses. The ifit5 can be upregulated by type I interferons (IFNs) like IFITs, and the dependency of ifit5 expression on activation of the Jak/STAT pathway has also been confirmed ( 54 ). Since there was no gene induction in the RT-HKM cells incubated with the ferritin-only NPs, these results indicate that immunogenicity and antiviral activity of the IHNV-G fragment was developed via the ferritin platform, most likely through the type I IFN-mediated Jak/STAT signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Self-assembling ferritin nanoplatform for the development of infectious hematopoietic necrosis virus vaccine

Ahmadivand,

Krpetic,

Martínez

et al. 2024

Front. Immunol.

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Self-assembling protein nanoparticles are used as a novel vaccine design platform to improve the stability and immunogenicity of safe subunit vaccines, while providing broader protection against viral infections. Infectious Hematopoietic Necrosis virus (IHNV) is the causative agent of the WOAH-listed IHN diseases for which there are currently no therapeutic treatments and no globally available commercial vaccine. In this study, by genetically fusing the virus glycoprotein to the H. pylori ferritin as a scaffold, we constructed a self-assembling IHNV nanovaccine (FerritVac). Despite the introduction of an exogenous fragment, the FerritVac NPs show excellent stability same as Ferritin NPs under different storage, pH, and temperature conditions, mimicking the harsh gastrointestinal condition of the virus main host (trout). MTT viability assays showed no cytotoxicity of FerritVac or Ferritin NPs in zebrafish cell culture (ZFL cells) incubated with different doses of up to 100 µg/mL for 14 hours. FerritVac NPs also upregulated expression of innate antiviral immunity, IHNV, and other fish rhabdovirus infection gene markers (mx, vig1, ifit5, and isg-15) in the macrophage cells of the host. In this study, we demonstrate the development of a soluble recombinant glycoprotein of IHNV in the E. coli system using the ferritin self-assembling nanoplatform, as a biocompatible, stable, and effective foundation to rescue and produce soluble protein and enable oral administration and antiviral induction for development of a complete IHNV vaccine. This self-assembling protein nanocages as novel vaccine approach offers significant commercial potential for non-mammalian and enveloped viruses.

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Section: Discussionmentioning

confidence: 99%

Self-assembling ferritin nanoplatform for the development of infectious hematopoietic necrosis virus vaccine

Ahmadivand,

Krpetic,

Martínez

et al. 2024

Front. Immunol.

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“…Atlantic salmon mx2 , ifit5 , and ifna1 promoter constructs ( 38 ) were investigated, whereas pGL3-basic was included as empty vector control. The promoters for mx2 ( 35 ) and interferon induced protein with tetratricopeptide repeats 5 ( ifit5 ) ( 21 ) were synthesized as GeneArt String fragments by ThermoFisher and cloned into HindIII-linearized pGL3 Basic using the Infusion HD cloning kit (Takara). One day after transfection, medium was replaced with 100 µl of neat L15 again, and transfection medium (10 µl of MEM with 0.3 µl of TransIT and 200 ng of stimulant) for HMW poly I:C or low –molecular weight (LMW) poly I:C was added.…”

Section: Methodsmentioning

confidence: 99%

“…IPNV infection in vitro does not induce IFN expression in certain cell types (10, 17), and several IPNV proteins have been shown to inhibit ifna1 expression (18). Salmonid alphavirus (SAV), an enveloped ssRNA virus, is another highly pathogenic salmonid virus, but it strongly induces IFN responses in infected cell lines, in contrast to IPNV (19)(20)(21)(22). An investigation into the role of key components of the PRR signaling that leads to IFN expression can help to gain more insight in these hostpathogen interactions.…”

Section: Introductionmentioning

confidence: 99%

CRISPR-Cas– induced IRF3 and MAVS knockouts in a salmonid cell line disrupt PRR signaling and affect viral replication

van der Wal,

Nordli,

Akandwanaho

et al. 2023

Front. Immunol.

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BackgroundInterferon (IFN) responses are critical in the resolution of viral infections and are actively targeted by many viruses. They also play a role in inducing protective responses after vaccination and have been successfully tested as vaccine adjuvants. IFN responses are well conserved and function very similar in teleosts and mammals. Like in mammals, IFN responses in piscine cells are initiated by intracellular detection of the viral infection by different pattern recognition receptors. Upon the recognition of viral components, IFN responses are rapidly induced to combat the infection. However, many viruses may still replicate and be able to inhibit or circumvent the IFN response by different means.MethodsBy employing CRISPR Cas9 technology, we have disrupted proteins that are central for IFN signaling in the salmonid cell line CHSE-214. We successfully generated KO clones for the mitochondrial antiviral signaling protein MAVS, the transcription factors IRF3 and IRF7-1, as well as a double KO for IRF7-1/3 using an optimized protocol for delivery of CRISPR-Cas ribonucleoproteins through nucleofection.ResultsWe found that MAVS and IRF3 KOs inhibited IFN and IFN-stimulated gene induction after intracellular poly I:C stimulation as determined through gene expression and promoter activation assays. In contrast, the IRF7-1 KO had no clear effect. This shows that MAVS and IRF3 are essential for initiation of intracellular RNA-induced IFN responses in CHSE-214 cells. To elucidate viral interference with IFN induction pathways, the KOs were infected with Salmon alphavirus 3 (SAV3) and infectious pancreatic necrosis virus (IPNV). SAV3 infection in control and IRF7-1 KO cells yielded similar titers and no cytopathic effect, while IRF3 and MAVS KOs presented with severe cytopathic effect and increased titers 6 days after SAV 3 infection. In contrast, IPNV yields were reduced in IRF3 and MAVS KOs, suggesting a dependency on interactions between viral proteins and pattern recognition receptor signaling components during viral replication.ConclusionAside from more insight in this signaling in salmonids, our results indicate a possible method to increase viral titers in salmonid cells.

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“…Similar to viral infections of carp, the up-regulation of gig or gig-like gene expression has been reported in ISAV-infected salmon [ 60 ]. The transcriptional activation of gig along with that of mx and vig/viperin has been observed in salmon between 2 and 4 weeks after challenge with SAV [ 61 , 62 , 63 ].…”

Section: Ssrna Virusesmentioning

confidence: 99%

Fish Innate Immune Response to Viral Infection—An Overview of Five Major Antiviral Genes

Ortega-Villaizán¹,

Chico²,

Pérez³

2022

Viruses

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Fish viral diseases represent a constant threat to aquaculture production. Thus, a better understanding of the cellular mechanisms involved in establishing an antiviral state associated with protection against virus replication and pathogenesis is paramount for a sustainable aquaculture industry. This review summarizes the current state of knowledge on five selected host innate immune-related genes in response to the most relevant viral pathogens in fish farming. Viruses have been classified as ssRNA, dsRNA, and dsDNA according to their genomes, in order to shed light on what those viruses may share in common and what response may be virus-specific, both in vitro (cell culture) as well as in vivo. Special emphasis has been put on trying to identify markers of resistance to viral pathogenesis. That is, those genes more often associated with protection against viral disease, a key issue bearing in mind potential applications into the aquaculture industry.

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Infection and microbial molecular motifs modulate transcription of the interferon-inducible gene ifit5 in a teleost fish

Cited by 5 publications

References 86 publications

Self-assembling ferritin nanoplatform for the development of infectious hematopoietic necrosis virus vaccine

Self-assembling ferritin nanoplatform for the development of infectious hematopoietic necrosis virus vaccine

CRISPR-Cas– induced IRF3 and MAVS knockouts in a salmonid cell line disrupt PRR signaling and affect viral replication

Fish Innate Immune Response to Viral Infection—An Overview of Five Major Antiviral Genes

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