scholarly journals Reovirus σ3 protein limits interferon expression and cell death induction

2020 ◽  
Author(s):  
Katherine E Roebke ◽  
Yingying Guo ◽  
John S. L. Parker ◽  
Pranav Danthi
Keyword(s):  
Cell Death ◽  
Capsid Protein ◽  
Rna Synthesis ◽  
Innate Immune ◽  
Type I ◽  
Outer Capsid Protein ◽  
Immune Signaling ◽  
Innate Immune Signaling ◽  
Dsrna Binding ◽  
Outer Capsid

ABSTRACTInduction of necroptosis by mammalian reovirus requires both type I interferon (IFN)-signaling and viral replication events that lead to production of progeny genomic dsRNA. The reovirus outer capsid protein µ1 negatively regulates reovirus-induced necroptosis by limiting RNA synthesis. To determine if the outer capsid protein σ3, which interacts with µ1, also functions in regulating cell death, we used siRNA-mediated knockdown. Similar to that observed by diminishment of µ1 expression, knockdown of newly synthesized σ3 enhances necroptosis. σ3 knockdown does not impact reovirus RNA synthesis. Instead, this increase in necroptosis following σ3 knockdown is accompanied by an increase in IFN production. Furthermore, ectopic expression of σ3 is sufficient to block IFN expression following infection. Surprisingly, the capacity of σ3 protein to bind dsRNA does not impact its capacity to diminish production of IFN. Consistent with this, infection with a virus harboring a mutation in the dsRNA binding domain of σ3 does not result in enhanced production of IFN or cell death. Together, these data suggest that σ3 limits the production of IFN to control innate immune signaling and cell death following infection through a mechanism that is independent of its dsRNA binding capacity.IMPORTANCEWe use mammalian reovirus as a model to study how virus infection modulates innate immune signaling and cell death induction. Here we sought to determine how viral factors regulate these processes. Our work highlights a previously unknown role for the reovirus outer capsid protein σ3 in limiting the induction of a necrotic form of cell death called necroptosis. Induction of cell death by necroptosis requires production of interferon. σ3 limits the induction of necroptosis by preventing excessive production of interferon following infection.

scholarly journals Reovirus σ3 Protein Limits Interferon Expression and Cell Death Induction

2020 ◽  
Vol 94 (22) ◽  
Author(s):  
Katherine E. Roebke ◽  
Yingying Guo ◽  
John S. L. Parker ◽  
Pranav Danthi
Keyword(s):  
Cell Death ◽  
Capsid Protein ◽  
Rna Synthesis ◽  
Innate Immune ◽  
Type I ◽  
Outer Capsid Protein ◽  
Immune Signaling ◽  
Innate Immune Signaling ◽  
Dsrna Binding ◽  
Outer Capsid

ABSTRACT Induction of necroptosis by mammalian reovirus requires both type I interferon (IFN)-signaling and viral replication events that lead to production of progeny genomic double-stranded RNA (dsRNA). The reovirus outer capsid protein μ1 negatively regulates reovirus-induced necroptosis by limiting RNA synthesis. To determine if the outer capsid protein σ3, which interacts with μ1, also functions in regulating necroptosis, we used small interfering RNA (siRNA)-mediated knockdown. Similarly to what was observed in diminishment of μ1 expression, knockdown of newly synthesized σ3 enhances necroptosis. Knockdown of σ3 does not impact reovirus RNA synthesis. Instead, this increase in necroptosis following σ3 knockdown is accompanied by an increase in IFN production. Furthermore, ectopic expression of σ3 is sufficient to block IFN expression following infection. Surprisingly, the capacity of σ3 protein to bind dsRNA does not impact its capacity to diminish production of IFN. Consistent with this, infection with a virus harboring a mutation in the dsRNA binding domain of σ3 does not result in enhanced production of IFN or necroptosis. Together, these data suggest that σ3 limits the production of IFN to control innate immune signaling and necroptosis following infection through a mechanism that is independent of its dsRNA binding capacity. IMPORTANCE We use mammalian reovirus as a model to study how virus infection modulates innate immune signaling and cell death induction. Here, we sought to determine how viral factors regulate these processes. Our work highlights a previously unknown role for the reovirus outer capsid protein σ3 in limiting the induction of a necrotic form of cell death called necroptosis. Induction of cell death by necroptosis requires production of interferon. The σ3 protein limits the induction of necroptosis by preventing excessive production of interferon following infection.

scholarly journals MAVS: A Two-Sided CARD Mediating Antiviral Innate Immune Signaling and Regulating Immune Homeostasis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yunqiang Chen ◽  
Yuheng Shi ◽  
Jing Wu ◽  
Nan Qi
Keyword(s):  
Signal Transduction ◽  
Innate Immune ◽  
Immune Homeostasis ◽  
Type I ◽  
Interferon Signaling ◽  
Immune Signaling ◽  
Post Translational Modifications ◽  
Innate Immune Signaling ◽  
Mitochondrial Antiviral Signaling ◽  
Mitochondrial Antiviral Signaling Protein

Mitochondrial antiviral signaling protein (MAVS) functions as a “switch” in the immune signal transduction against most RNA viruses. Upon viral infection, MAVS forms prion-like aggregates by receiving the cytosolic RNA sensor retinoic acid-inducible gene I-activated signaling and further activates/switches on the type I interferon signaling. While under resting state, MAVS is prevented from spontaneously aggregating to switch off the signal transduction and maintain immune homeostasis. Due to the dual role in antiviral signal transduction and immune homeostasis, MAVS has emerged as the central regulation target by both viruses and hosts. Recently, researchers show increasing interest in viral evasion strategies and immune homeostasis regulations targeting MAVS, especially focusing on the post-translational modifications of MAVS, such as ubiquitination and phosphorylation. This review summarizes the regulations of MAVS in antiviral innate immune signaling transduction and immune homeostasis maintenance.

scholarly journals IMMU-34. ATRX MUTATIONS PREDICT RESPONSE TO INNATE BASED THERAPY IN GLIOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi126-vi126
Author(s):  
Michelle Bowie ◽  
Seethalakshmi Hariharan ◽  
Janell Hostettler ◽  
Kristen Roso ◽  
Yiping He ◽  
...  
Keyword(s):  
Cell Lines ◽  
Glioma Cell ◽  
Innate Immune ◽  
Type I ◽  
Loss Of Function ◽  
Who Grade ◽  
Immune Signaling ◽  
Innate Immune Signaling ◽  
Recurrent Mutations ◽  
Glioma Cell Lines

Abstract BACKGROUND Innate based immunotherapies are becoming increasingly important for treating brain tumor patients. Gliomas carry recurrent mutations in regulatory genes that control innate immune signaling responses. About 71% of adult WHO grade II and III gliomas and 57% of secondary glioblastomas also carry a loss-of-function mutation in the ATRX gene. ATRX is a SWI-SNF chromatin remodeling protein that has major roles in processes such as cell cycle regulation and maintenance of genomic stability. Recent studies have implicated ATRX in dysfunctional innate immune signaling in cancer cells. However, the role of ATRX in mediating innate immune responses has not been investigated in gliomas. METHODS AND RESULTS Human and mouse glioma cell lines from a variety of genetic contexts have been examined including models which carry IDH/ATRX mutations, IDH 1p-/19q- and ATRX -/- status. Additionally, using Crispr-Cas9 technology and cloning cell lines with ATRX deletions, we have derived a series of immune competent and nude mice models. Treating these cell lines with double-stranded RNA based innate stimuli led to an enhanced early induction in phospho-interferon regulatory factor 3 (IRF3) and late induction in phospho-STAT1 in the ATRX knockout (KO) cell lines. A differential increase in interferon-stimulated gene 15 (ISG15) release was also noted in the ATRX KO cell lines, further suggesting that ATRX deletion may enable a potent activation of type I interferon production. A combination of patient-derived glioma cell lines in xenograft models and syngeneic murine glioma models derived from ATRX KO cell lines and controls confirm a survival advantage in both immuno-competent mice and xenografts. Our models are under evaluation with PVSRIPO and other innate based RNA therapies. CONCLUSION Our data suggests that ATRX mutations may confer sensitivity to RNA-based innate immune signaling agonists in gliomas. This potential vulnerability can be targeted in future therapies.

scholarly journals STING signaling and host defense against microbial infection

2019 ◽  
Vol 51 (12) ◽  
pp. 1-10 ◽  
Author(s):  
Jeonghyun Ahn ◽  
Glen N. Barber
Keyword(s):  
Host Defense ◽  
Innate Immune ◽  
Type I Interferons ◽  
Type I ◽  
Microbial Infection ◽  
Immune Signaling ◽  
Pathogen Invasion ◽  
Innate Immune Signaling ◽  
Specific Pathogen ◽  
Microbial Dna

AbstractThe first line of host defense against infectious agents involves activation of innate immune signaling pathways that recognize specific pathogen-associated molecular patterns (PAMPs). Key triggers of innate immune signaling are now known to include microbial-specific nucleic acid, which is rapidly detected in the cytosol of the cell. For example, RIG-I-like receptors (RLRs) have evolved to detect viral RNA species and to activate the production of host defense molecules and cytokines that stimulate adaptive immune responses. In addition, host defense countermeasures, including the production of type I interferons (IFNs), can also be triggered by microbial DNA from bacteria, viruses and perhaps parasites and are regulated by the cytosolic sensor, stimulator of interferon genes (STING). STING-dependent signaling is initiated by cyclic dinucleotides (CDNs) generated by intracellular bacteria following infection. CDNs can also be synthesized by a cellular synthase, cGAS, following interaction with invasive cytosolic self-DNA or microbial DNA species. The importance of STING signaling in host defense is evident since numerous pathogens have developed strategies to prevent STING function. Here, we review the relevance of STING-controlled innate immune signaling in host defense against pathogen invasion, including microbial endeavors to subvert this critical process.

scholarly journals Cell Entry-Independent Role for the Reovirus μ1 Protein in Regulating Necroptosis and the Accumulation of Viral Gene Products

2019 ◽  
Vol 93 (11) ◽  
Author(s):  
Katherine E. Roebke ◽  
Pranav Danthi
Keyword(s):  
Cell Death ◽  
Capsid Protein ◽  
Apoptotic Cell ◽  
Guanidine Hydrochloride ◽  
Viral Gene ◽  
Gene Products ◽  
Minus Strand ◽  
Outer Capsid Protein ◽  
Infected Cells ◽  
Outer Capsid

ABSTRACTThe reovirus outer capsid protein μ1 regulates cell death in infected cells. To distinguish between the roles of incoming, capsid-associated, and newly synthesized μ1, we used small interfering RNA (siRNA)-mediated knockdown. Loss of newly synthesized μ1 protein does not affect apoptotic cell death in HeLa cells but enhances necroptosis in L929 cells. Knockdown of μ1 also affects aspects of viral replication. We found that, while μ1 knockdown results in diminished release of infectious viral progeny from infected cells, viral minus-strand RNA, plus-strand RNA, and proteins that are not targeted by the μ1 siRNA accumulate to a greater extent than in control siRNA-treated cells. Furthermore, we observed a decrease in sensitivity of these viral products to inhibition by guanidine hydrochloride (GuHCl) (which targets minus-strand synthesis to produce double-stranded RNA) when μ1 is knocked down. Following μ1 knockdown, cell death is also less sensitive to treatment with GuHCl. Our studies suggest that the absence of μ1 allows enhanced transcriptional activity of newly synthesized cores and the consequent accumulation of viral gene products. We speculate that enhanced accumulation and detection of these gene products due to μ1 knockdown potentiates receptor-interacting protein 3 (RIP3)-dependent cell death.IMPORTANCEWe used mammalian reovirus as a model to study how virus infections result in cell death. Here, we sought to determine how viral factors regulate cell death. Our work highlights a previously unknown role for the reovirus outer capsid protein μ1 in limiting the induction of a necrotic form of cell death called necroptosis. Induction of cell death by necroptosis requires the detection of viral gene products late in infection; μ1 limits cell death by this mechanism because it prevents excessive accumulation of viral gene products that trigger cell death.

scholarly journals STAT5: a Target of Antagonism by Neurotropic Flaviviruses

2019 ◽  
Vol 93 (23) ◽  
Author(s):  
Matthew G. Zimmerman ◽  
James R. Bowen ◽  
Circe E. McDonald ◽  
Ellen Young ◽  
Ralph S. Baric ◽  
...  
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Type I ◽  
Molecular Signatures ◽  
Zikv Infection ◽  
Immune Signaling ◽  
Gm Csf ◽  
Innate Immune Signaling ◽  
Significant Public Health ◽  
Dengue Virus Serotypes

ABSTRACT Flaviviruses are a diverse group of arthropod-borne viruses responsible for numerous significant public health threats; therefore, understanding the interactions between these viruses and the human immune response remains vital. West Nile virus (WNV) and Zika virus (ZIKV) infect human dendritic cells (DCs) and can block antiviral immune responses in DCs. Previously, we used mRNA sequencing and weighted gene coexpression network analysis (WGCNA) to define molecular signatures of antiviral DC responses following activation of innate immune signaling (RIG-I, MDA5, or type I interferon [IFN] signaling) or infection with WNV. Using this approach, we found that several genes involved in T cell cosignaling and antigen processing were not enriched in DCs during WNV infection. Using cis-regulatory sequence analysis, STAT5 was identified as a regulator of DC activation and immune responses downstream of innate immune signaling that was not activated during either WNV or ZIKV infection. Mechanistically, WNV and ZIKV actively blocked STAT5 phosphorylation downstream of RIG-I, IFN-β, and interleukin-4 (IL-4), but not granulocyte-macrophage colony-stimulating factor (GM-CSF), signaling. Unexpectedly, dengue virus serotypes 1 to 4 (DENV1 to DENV4) and the yellow fever 17D vaccine strain (YFV-17D) did not antagonize STAT5 phosphorylation. In contrast to WNV, ZIKV inhibited JAK1 and TYK2 phosphorylation following type I IFN treatment, suggesting divergent mechanisms used by these viruses to inhibit STAT5 activation. Combined, these findings identify STAT5 as a target of antagonism by specific pathogenic flaviviruses to subvert the immune response in infected DCs. IMPORTANCE Flaviviruses are a diverse group of insect-borne viruses responsible for numerous significant public health threats. Previously, we used a computational biology approach to define molecular signatures of antiviral DC responses following activation of innate immune signaling or infection with West Nile virus (WNV). In this work, we identify STAT5 as a regulator of DC activation and antiviral immune responses downstream of innate immune signaling that was not activated during either WNV or Zika virus (ZIKV) infection. WNV and ZIKV actively blocked STAT5 phosphorylation downstream of RIG-I, IFN-β, and IL-4, but not GM-CSF, signaling. However, other related flaviviruses, dengue virus serotypes 1 to 4 and the yellow fever 17D vaccine strain, did not antagonize STAT5 phosphorylation. Mechanistically, WNV and ZIKV showed differential inhibition of Jak kinases upstream of STAT5, suggesting divergent countermeasures to inhibit STAT5 activation. Combined, these findings identify STAT5 as a target of antagonism by specific pathogenic flaviviruses to subvert antiviral immune responses in human DCs.

scholarly journals Distinct binding sites for zinc and double-stranded RNA in the reovirus outer capsid protein sigma 3.

1988 ◽  
Vol 8 (1) ◽  
pp. 273-283 ◽  
Author(s):  
L A Schiff ◽  
M L Nibert ◽  
M S Co ◽  
E G Brown ◽  
B N Fields
Keyword(s):  
Transcription Factor ◽  
Capsid Protein ◽  
Binding Activity ◽  
Zinc Binding ◽  
Outer Capsid Protein ◽  
Double Stranded Rna ◽  
Transcription Factor Iiia ◽  
Terminal Fragment ◽  
Dsrna Binding ◽  
Outer Capsid

By atomic absorption analysis, we determined that the reovirus outer capsid protein sigma 3, which binds double-stranded RNA (dsRNA), is a zinc metalloprotein. Using Northwestern blots and a novel zinc blotting technique, we localized the zinc- and dsRNA-binding activities of sigma 3 to distinct V8 protease-generated fragments. Zinc-binding activity was contained within an amino-terminal fragment that contained a transcription factor IIIA-like zinc-binding sequence, and dsRNA-binding activity was associated with a carboxy-terminal fragment. By these techniques, new zinc- and dsRNA-binding activities were also detected in reovirus core proteins. A sequence similarity was observed between the catalytic site of the picornavirus proteases and the transcription factor IIIA-like zinc-binding site within sigma 3. We suggest that the zinc- and dsRNA-binding activities of sigma 3 may be important for its proposed regulatory effects on viral and host cell transcription and translation.

scholarly journals Dependency of Spliceosomal Mutant MDS on Innate Immune Signaling

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 937-937
Author(s):  
Stanley C Lee ◽  
Khrystyna North ◽  
Chi-Chao Chen ◽  
Eunhee Kim ◽  
Sydney X. Lu ◽  
...  
Keyword(s):  
Cell Survival ◽  
Myeloid Cells ◽  
K562 Cells ◽  
Genetic Alterations ◽  
Innate Immune ◽  
Type I ◽  
Immune Signaling ◽  
Innate Immune Signaling ◽  
Genes Encoding ◽  
Mutant Cells

Abstract Mutations in genes encoding RNA splicing factors constitute the most common class of genetic alterations in patients with myelodysplastic syndromes (MDS). These occur as heterozygous point mutations at specific amino acid residues in SF3B1, SRSF2, and U2AF1, and are almost always mutually exclusive with one another. Recent studies have identified that mutations in each of these genes results in activation of the innate immune signaling through altered splicing of mRNAs encoding key enzymes in this pathway. Now, through an unbiased genetic screen as well as focused genetic studies, we have identified that SF3B1-mutant MDS depends on aberrant immune signaling for cell survival. Recent work has identified that aberrant splicing of MAP3K7 (also known as TAK1; TGF-b Activating Kinase 1) is pervasive across SF3B1-mutant human and mouse cells and results in reduced MAP3K7 protein expression and increased NF-κB signaling. Consistent with this, Map3k7 haploinsufficiency in myeloid cells is known to cause myeloproliferation, while at the same time, complete loss of Map3k7 is intolerable for hematopoietic cells. We therefore hypothesized that partial inhibition of MAP3K7 might preferentially impact SF3B1-mutant cells. To test this hypothesis, we generated mice with inducible deletion of 1 or 2 copies of Map3k7 (Mx1-cre Map3k7fl/+,Mx1-cre Map3k7fl/fl) alone or in the presence of mutant Sf3b1K700E (Mx1-cre Map3k7fl/+Sf3b1K700E/+,Mx1-cre Map3k7fl/flSf3b1K700E/+), along with all controls (Mx1-cre Sf3b1+/+ Map3k7+/+ (Wildtype; WT) and Mx1-cre Sf3b1K700E/+ mice). We then performed bone marrow transplantation (BMT) to assess the effect of Map3k7 deletion on aberrant hematopoiesis driven by mutant SF3B1. Consistent with prior reports, heterozygous deletion of Map3k7did not affect repopulating potential in BMT assays compared to controls while homozygous deletion of Map3k7 resulted in complete failure of hematopoiesis (Figure A). Interestingly, however, in the presence of Sf3b1K700E mutation, deletion of a single copy of Map3k7 completely rescued the hematopoietic defects characteristic of mutant SF3B1 in both mature and immature cells (Figure B-C). These data suggest that inhibition of residual MAP3K7 function may preferentially target SF3B1-mutant MDS cells. In parallel to the above studies, we also performed a negative selection RNAi screen to uncover novel genetic dependencies in SF3B1-mutant myeloid neoplasms. We performed pooled lentiviral infection of shRNAs targeting ~2,200 genes encoding proteins which are drug targets ("The Druggable Genome") under the control of a doxycycline-inducible vector in isogenic K562 cells expressing the two most commonly occurring SF3B1 mutations, SF3B1K666N and SF3B1K700E, from the endogenous SF3B1 locus. Two individual clones per SF3B1-mutant line were used to improve the robustness of the screen. On Day 21 following shRNA activation, genes with ≥3 shRNAs depleted in SF3B1-mutant cells while remaining unchanged in parental K562 cells were selected. This identified 101 candidates that are potentially synthetic-lethal with SF3B1 mutation (Figure D). Interestingly, pathway analysis of these potential candidates revealed of genes involved in immune and inflammatory signaling as well as in metabolic processes (Figure E). Further target validation was performed using in vitro competitive growth assay in K562 cells, and another set of SF3B1 isogenic lymphoid leukemia cell lines (NALM-6) expressing the same mutations. This revealed consistent dependency of SF3B1-mutant cells on STAT1, an essential component of the interferon (IFN) signaling pathway (Figure F). Upon exposure to Type-I IFNs, SF3B1-mutant K562 cells showed increased transcriptional response in IFN-responsive genes containing interferon stimulated response elements (ISREs) compared with SF3B1 WT cells (Figure G). These data highlight that SF3B1-mutant cells are hyper-responsive to IFN signaling and require intact IFN-signaling responses for cell survival. Taken together, the above studies indicate that sustained IFN signaling as well as activated innate immune signaling downstream of TAK1 are required for the survival of SF3B1-mutant myeloid cells. These results therefore have important therapeutic implications as they suggest that pharmacologic inhibition of STAT1/Type I IFN activation and/or TAK1 may serve as important therapeutic agents for SF3B1-mutant MDS. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

scholarly journals Cell entry-independent role for the reovirus μ1 protein in regulating necroptosis and the accumulation of viral gene products

2019 ◽  
Author(s):  
Katherine E Roebke ◽  
Pranav Danthi
Keyword(s):  
Cell Death ◽  
Capsid Protein ◽  
Apoptotic Cell ◽  
Viral Gene ◽  
Gene Products ◽  
Minus Strand ◽  
Virus Infections ◽  
Outer Capsid Protein ◽  
Infected Cells ◽  
Outer Capsid

ABSTRACTThe reovirus outer capsid protein μ1 regulates cell death in infected cells. To distinguish between the role of incoming, capsid-associated and newly synthesized μ1, we used siRNA-mediated knockdown. Loss of newly synthesized μ1 protein does not impact apoptotic cell death in HeLa cells but enhances necroptosis in L929 cells. Knockdown of μ1 also impacts aspects of viral replication. We found that while μ1 knockdown results in diminished release of infectious viral progeny from infected cells, viral minus strand RNA, plus strand RNA, and proteins that are not targeted by the μ1 siRNA accumulate to a greater extent when compared to control siRNA-treated cells. Furthermore, we observe a decrease in sensitivity of these viral products to inhibition by GuHCl (which targets minus strand synthesis to produce dsRNA) when μ1 is knocked down. Following μ1 knockdown, cell death is also less sensitive to treatment with GuHCl. Our studies suggest that the absence of μ1 allows enhanced transcriptional activity of newly synthesized cores and the consequent accumulation of viral gene products. We speculate that enhanced accumulation and detection of these gene products due to a μ1 knockdown potentiates RIP3 dependent cell death.IMPORTANCEWe use mammalian reovirus as a model to study how virus infections result in cell death. Here, we sought to determine how viral factors regulate cell death. Our work highlights a previously unknown role for reovirus outer capsid protein μ1 in limiting the induction of a necrotic form of cell death called necroptosis. Induction of cell death by necroptosis requires the detection of viral gene products late in infection. μ1 limits cell death by this mechanism because it prevents excessive accumulation of viral gene products that trigger cell death.

scholarly journals FIP200 restricts RNA virus infection by facilitating RIG-I activation

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Lingyan Wang ◽  
Kun Song ◽  
Wenzhuo Hao ◽  
Yakun Wu ◽  
Girish Patil ◽  
...  
Keyword(s):  
Virus Infection ◽  
Rna Virus ◽  
Innate Immune ◽  
Host Susceptibility ◽  
In Vivo Studies ◽  
Helicase Domain ◽  
Type I ◽  
Immune Signaling ◽  
Innate Immune Signaling

AbstractRetinoic acid-inducible gene I (RIG-I) senses viral RNA and instigates an innate immune signaling cascade to induce type I interferon expression. Currently, the regulatory mechanisms controlling RIG-I activation remain to be fully elucidated. Here we show that the FAK family kinase-interacting protein of 200 kDa (FIP200) facilitates RIG-I activation. FIP200 deficiency impaired RIG-I signaling and increased host susceptibility to RNA virus infection. In vivo studies further demonstrated FIP200 knockout mice were more susceptible to RNA virus infection due to the reduced innate immune response. Mechanistic studies revealed that FIP200 competed with the helicase domain of RIG-I for interaction with the two tandem caspase activation and recruitment domains (2CARD), thereby facilitating the release of 2CARD from the suppression status. Furthermore, FIP200 formed a dimer and facilitated 2CARD oligomerization, thereby promoting RIG-I activation. Taken together, our study defines FIP200 as an innate immune signaling molecule that positively regulates RIG-I activation.

Sign in / Sign up

Export Citation Format

Share Document