Host Antiviral Innate Immunity Research Articles

Vaccinia virus Tiantan strain blocks host antiviral innate immunity and programmed cell death by disrupting gene expression

The vaccinia virus Tiantan (VTT) is widely utilized as a smallpox vaccine in China and holds significant importance in the prevention of diseases stemming from poxvirus infections. Nevertheless, few studies have investigated the influence of VTT infection on host gene expression. In this study, we constructed time series transcriptomic profiles of HeLa cells infected with both VTT and western reserve (WR) strains. We observed similar patterns of viral gene expression, while the expression levels of host genes varied between the two strains. There was an immediate and significant repression of host gene expression, particularly in genes associated with oxidative phosphorylation. Conversely, genes involved in nerve growth factor (NGF)-stimulated transcription were significantly activated. The upregulation of genes linked to the ribonucleic acid (RNA)-induced silencing complex (RISC) suggested a potential role for posttranscriptional regulation in the interaction between the vaccinia virus and the host. In the later stages of infection, pathways such as extracellular matrix organization, neutrophil degranulation, complement and interferon responses, translation, and programmed cell death are largely inhibited. A significant number of host genes exhibit correlations with changes in the expression levels of viral genes. The host genes that are negatively correlated with viral genes are mainly enriched in pathways associated with translation and the response to viral infection. This study significantly contributes to advancing our understanding of the dynamics between the vaccinia virus and the host, improving the application of VTTs and facilitating the development of effective vaccines against diseases such as smallpox and monkeypox.

TRIM26 facilitates PRV infection through NDP52-mediated autophagic degradation of MAVS

Pseudorabies virus (PRV) has evolved multiple strategies to evade host antiviral responses to benefit virus replication and establish persistent infection. Recently, tripartite motif 26 (TRIM26), a TRIM family protein, has been shown to be involved in a broad range of biological processes involved in innate immunity, especially in regulating viral infection. Herein, we found that the expression of TRIM26 was significantly induced after PRV infection. Surprisingly, the overexpression of TRIM26 promoted PRV production, while the depletion of this protein inhibited virus replication, suggesting that TRIM26 could positively regulate PRV infection. Further analysis revealed that TRIM26 negatively regulates the innate immune response by targeting the RIG-I-triggered type I interferon signalling pathway. TRIM26 was physically associated with MAVS independent of viral infection and reduced MAVS expression. Mechanistically, we found that NDP52 interacted with both TRIM26 and MAVS and that TRIM26-induced MAVS degradation was almost entirely blocked in NDP52-knockdown cells, demonstrating that TRIM26 degrades MAVS through NDP52-mediated selective autophagy. Our results reveal a novel mechanism by which PRV escapes host antiviral innate immunity and provide insights into the crosstalk among virus infection, autophagy, and the innate immune response.

African swine fever virus pB475L evades host antiviral innate immunity via targeting STAT2 to inhibit IFN-I signaling

African swine fever virus (ASFV) causes severe disease in domestic pigs and wild boars, seriously threatening the development of the global pig industry. Type I interferon (IFN-I) is an important component of innate immunity, inducing the transcription and expression of antiviral cytokines by activating Janus-activated kinase-signal transducer and activation of transcription (JAK-STAT) signal transduction. However, the underlying molecular mechanisms by which ASFV antagonizes IFN-I signaling have not been fully elucidated. Therefore, using co-immunoprecipitation, confocal microscopy and dual luciferase reporter assay methods, we investigated these mechanisms and identified a novel ASFV immunosuppressive protein, pB475L, which interacts with the C-terminal domain of STAT2. Consequently, pB475L inhibited IFN-I signaling by inhibiting STAT1 and STAT2 heterodimerization and nuclear translocation. Furthermore, we constructed an ASFV-B475L7PM mutant strain by homologous recombination, finding that ASFV-B475L7PM attenuated the inhibitory effects on IFN-I signaling compared to wild-type ASFV. In summary, this study reveals a new mechanism by which ASFV impairs host innate immunity.

Pseudorabies virus usurps non-muscle myosin heavy chain IIA to dampen viral DNA recognition by cGAS for antagonism of host antiviral innate immunity.

Alphaherpesvirus pseudorabies virus (PRV) causes severe economic losses to the global pig industry and has garnered increasing attention due to its broad host range including humans. PRV has developed a variety of strategies to antagonize host antiviral innate immunity. However, the underlying mechanisms have not been fully elucidated. In our previous work, we demonstrated that non-muscle myosin heavy chain IIA (NMHC-IIA), a multifunctional cytoskeleton protein, attenuates innate immune responses triggered by RNA viruses. In the current study, we reported a previously unrecognized role of NMHC-IIA in counteracting PRV-induced cyclic GMP-AMP synthase (cGAS)-dependent type I interferon (IFN-I) production. Mechanistically, PRV infection led to an elevation of NMHC-IIA, strengthening the interaction between poly (ADP-ribose) polymerase 1 (PARP1) and cGAS. This interaction impeded cGAS recognition of PRV DNA and hindered downstream signaling activation. Conversely, inhibition of NMHC-IIA by Blebbistatin triggered innate immune responses and enhanced resistance to PRV proliferation both in vitro and in vivo. Taken together, our findings unveil that PRV utilizes NMHC-IIA to antagonize host antiviral immune responses via impairing DNA sensing by cGAS. This in-depth understanding of PRV immunosuppression not only provides insights for potential PRV treatment strategies but also highlights NMHC-IIA as a versatile immunosuppressive regulator usurped by both DNA and RNA viruses. Consequently, NMHC-IIA holds promise as a target for the development of broad-spectrum antiviral drugs.IMPORTANCECyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) axis plays a vital role in counteracting alphaherpesvirus infections. Alphaherpesviruses exploit various strategies for antagonizing cGAS-STING-mediated antiviral immune responses. However, limited examples of pseudorabies virus (PRV)-caused immunosuppression have been documented. Our findings reveal a novel role of non-muscle myosin heavy chain IIA (NMHC-IIA) in suppressing PRV-triggered innate immune responses to facilitate viral propagation both in vitro and in vivo. In detail, NMHC-IIA recruits poly (ADP-ribose) polymerase 1 (PARP1) to augment its interaction with cGAS, which impairs cGAS recognition of PRV DNA. Building on our previous demonstration of NMHC-IIA's immunosuppressive role during RNA virus infections, these findings indicate that NMHC-IIA acts as a broad-spectrum suppressor of host antiviral innate immunity in response to both DNA and RNA viruses. Therefore, NMHC-IIA will be a promising target for the development of comprehensive antiviral strategies.

African swine fever virus A137R protein inhibits NF-κB activation via suppression of MyD88 signaling in PK15 and 3D4/21 cells in vitro

African swine fever (ASF) is an infectious disease with high mortality caused by African swine fever virus (ASFV), which poses a great threat to the global swine industry. ASFV has evolved multiple strategies to evade host antiviral innate immunity by perturbing inflammatory responses and interferon production. However, the molecular mechanisms underlying manipulation of inflammatory responses by ASFV proteins are not fully understood. Here, we report that A137R protein of ASFV is a key suppressor of host inflammatory responses. Ectopic expression of ASFV A137R in HEK293T cells significantly inhibited the activation of IL-8 and NF-κB promoters triggered by Sendai virus (SeV), influenza A virus (IAV), or vesicular stomatitis virus (VSV). Accordingly, forced A137R expression caused a significant decrease in the production of several inflammatory cytokines such as IL-8, IL-6 and TNF-α in the cells infected with SeV or IAV. Similar results were obtained from experiments using A137R overexpressing PK15 and 3D4/21 cells infected with SeV or VSV. Furthermore, we observed that A137R impaired the activation of MAPK and NF-κB signaling pathways, as enhanced expression of A137R significantly decreased the phosphorylation of JNK, p38 and p65 respectively upon viral infection (SeV or IAV) and IL-1β treatment. Mechanistically, we found that A137R interacted with MyD88, and dampened MyD88-mediated activation of MAPK and NF-κB signaling. Together, these findings uncover a critical role of A137R in restraining host inflammatory responses, and improve our understanding of complicated mechanisms whereby ASFV evades innate immunity.

Housekeeping U1 snRNA facilitates antiviral innate immunity by promoting TRIM25-mediated RIG-I activation

U1 small nuclear RNA (snRNA) is an abundant and evolutionarily conserved 164-nucleotide RNA species that functions in pre-mRNA splicing, and it is considered to be a housekeeping non-coding RNA. However, the role of U1 snRNA in regulating host antiviral immunity remains largely unexplored. Here, we find that RNVU1-18, a U1 pseudogene, is significantly upregulated in the host infected with RNA viruses, including influenza and respiratory syncytial virus. Overexpression of U1 snRNA protects cells against RNA viruses, while knockdown of U1 snRNA leads to more viral burden invitro and invivo. Knockout of RNVU1-18 is sufficient to impair the type I interferon-dependent antiviral innate immunity. U1 snRNA is required to fully activate the retinoic acid-inducible gene I (RIG-I)-dependent antiviral signaling, since it interacts with tripartite motif 25 (TRIM25) and enhances the RIG-I-TRIM25 interaction to trigger K63-linked ubiquitination of RIG-I. Our study reveals the important role of housekeeping U1 snRNA in regulating host antiviral innate immunity and restricting RNA virus infection.

N6-methyladenosine modification positively regulate Japanese encephalitis virus replication

N6-methyladenosine (m6A) is present in diverse viral RNA and plays important regulatory roles in virus replication and host antiviral innate immunity. However, the role of m6A in regulating JEV replication has not been investigated. Here, we show that the JEV genome contains m6A modification upon infection of mouse neuroblast cells (neuro2a). JEV infection results in a decrease in the expression of m6A writer METTL3 in mouse brain tissue. METTL3 knockdown by siRNA leads to a substantial decrease in JEV replication and the production of progeny viruses at 48 hpi. Mechanically, JEV triggered a considerable increase in the innate immune response of METTL3 knockdown neuro2a cells compared to the control cells. Our study has revealed the distinctive m6A signatures of both the virus and host in neuro2a cells infected with JEV, illustrating the positive role of m6A modification in JEV infection. Our study further enhances understanding of the role of m6A modification in Flaviviridae viruses.

African swine fever virus proteins against host antiviral innate immunity and their implications for vaccine development.

African swine fever virus (ASFV) poses a significant threat to global swine populations, necessitating a profound understanding of viral strategies against host antiviral innate immunity. This review synthesizes current knowledge regarding ASFV proteins and their intricate interactions with host defenses. Noteworthy findings encompass the modulation of interferon signaling, manipulation of inflammatory pathways, and the impact on cellular apoptosis. The implications of these findings provide a foundation for advancing vaccine strategies against ASFV. In conclusion, this review consolidates current knowledge, emphasizing the adaptability of ASFV in subverting host immunity. Identified research gaps underscore the need for continued exploration, presenting opportunities for developing targeted vaccines. This synthesis provides a roadmap for future investigations, aiming to enhance our preparedness against the devastating impact of ASFV on global swine populations.

Correction for Zhu and Zheng, "The Race between Host Antiviral Innate Immunity and the Immune Evasion Strategies of Herpes Simplex Virus 1".

Correction for Zhu and Zheng, "The Race between Host Antiviral Innate Immunity and the Immune Evasion Strategies of Herpes Simplex Virus 1".

Prohibitin1 facilitates viral replication by impairing the RIG-I-like receptor signaling pathway.

Type I interferon (IFN-I), produced by the innate immune system, plays an essential role in host antiviral responses. Proper regulation of IFN-I production is required for the host to balance immune responses and prevent superfluous inflammation. IFN regulatory factor 3 (IRF3) and subsequent sensors are activated by RNA virus infection to induce IFN-I production. Therefore, proper regulation of IRF3 serves as an important way to control innate immunity and viral replication. Here, we first identified Prohibitin1 (PHB1) as a negative regulator of host IFN-I innate immune responses. Mechanistically, PHB1 inhibited the nucleus import of IRF3 by impairing its binding with importin subunit alpha-1 and importin subunit alpha-5. Our study demonstrates the mechanism by which PHB1 facilitates the replication of multiple RNA viruses and provides insights into the negative regulation of host immune responses.

Cellular Stress Responses against Coronavirus Infection: A Means of the Innate Antiviral Defense.

Cellular stress responses are crucial for maintaining cellular homeostasis. Stress granules (SGs), activated by eIF2α kinases in response to various stimuli, play a pivotal role in dealing with diverse stress conditions. Viral infection, as one kind of cellular stress, triggers specific cellular programs aimed at overcoming virus-induced stresses. Recent studies have revealed that virus-derived stress responses are tightly linked to the host's antiviral innate immunity. Virus infection-induced SGs act as platforms for antiviral sensors, facilitating the initiation of protective antiviral responses called "antiviral stress granules" (avSGs). However, many viruses, including coronaviruses, have evolved strategies to suppress avSG formation, thereby counteracting the host's immune responses. This review discusses the intricate relationship between cellular stress responses and antiviral innate immunity, with a specific focus on coronaviruses. Furthermore, the diverse mechanisms employed by viruses to counteract avSGs are described.

Herpes simplex virus type I glycoprotein L evades host antiviral innate immunity by abrogating the nuclear translocation of phosphorylated NF-κB sub-unit p65.

Nuclear factor (NF)-κB plays an important role in the innate immune response by inducing antiviral genes' expression. However, the herpes simplex virus 1 (HSV-1) virus has developed multiple ways to interfere with NF-κB activity to escape the host antiviral response. Here, we found that HSV-1 envelope glycoprotein L(gL) markedly inhibits interferon (IFN) production and its downstream antiviral genes. Our results showed that ectopic expression of gL inhibited IFN-β promoter activation, and decreased IFN-β production, the expression of IFN-stimulated genes (ISGs), and inhibited immunologic stimulant (poly I:C) induced activation of IFN signaling pathway. Depletion of gL by short interfering RNA (siRNA) significantly upregulated IFN-β and ISG production. Further study showed that the N-terminus of the gL bound to the Rel homology domain (RHD) of the p65 and concealed the nuclear localization signal of p65, thereby impeding the translocation of phosphorylated p65 to the nucleus. In summary, our findings indicated that the N-terminal of HSV-1 gL contributes to immune invasion by inhibiting the nuclear translocation of p65.

Porcine Epidemic Diarrhea Virus Antagonizes Host IFN-λ-Mediated Responses by Tilting Transcription Factor STAT1 toward Acetylation over Phosphorylation To Block Its Activation.

Porcine epidemic diarrhea virus (PEDV) is the main etiologic agent causing acute swine epidemic diarrhea, leading to severe economic losses to the pig industry. PEDV has evolved to deploy complicated antagonistic strategies to escape from host antiviral innate immunity. Our previous study demonstrated that PEDV downregulates histone deacetylase 1 (HDAC1) expression by binding viral nucleocapsid (N) protein to the transcription factor Sp1, inducing enhanced protein acetylation. We hypothesized that PEDV inhibition of HDAC1 expression would enhance acetylation of the molecules critical in innate immune signaling. Signal transducer and activator of transcription 1 (STAT1) is a crucial transcription factor regulating expression of interferon (IFN)-stimulated genes (ISGs) and anti-PEDV immune responses, as shown by overexpression, chemical inhibition, and gene knockdown in IPEC-J2 cells. We further show that PEDV infection and its N protein overexpression, although they upregulated STAT1 transcription level, could significantly block poly(I·C) and IFN-λ3-induced STAT1 phosphorylation and nuclear localization. Western blotting revealed that PEDV and its N protein promote STAT1 acetylation via downregulation of HDAC1. Enhanced STAT1 acetylation due to HDAC1 inhibition by PEDV or MS-275 (an HDAC1 inhibitor) impaired STAT1 phosphorylation, indicating that STAT1 acetylation negatively regulated its activation. These results, together with our recent report on PEDV N-mediated inhibition of Sp1, clearly indicate that PEDV manipulates the Sp1-HDAC1-STAT1 signaling axis to inhibit transcription of OAS1 and ISG15 in favor of its replication. This novel immune evasion mechanism is realized by suppression of STAT1 activation through preferential modulation of STAT1 acetylation over phosphorylation as a result of HDAC1 expression inhibition. IMPORTANCE PEDV has developed sophisticated evasion mechanisms to escape host IFN signaling via its structural and nonstructural proteins. STAT1 is one of the key transcription factors in regulating expression of ISGs. We found that PEDV and its N protein inhibit STAT1 phosphorylation and nuclear localization via inducing STAT1 acetylation as a result of HDAC1 downregulation, which, in turn, dampens the host IFN signaling activation. Our study demonstrates a novel mechanism that PEDV evades host antiviral innate immunity through manipulating the reciprocal relationship of STAT1 acetylation and phosphorylation. This provides new insights into the pathogenetic mechanisms of PEDV and even other coronaviruses.

Zebrafish MARCH7 negatively regulates IFN antiviral response by degrading TBK1

Membrane-associated RING-CH-type finger (MARCH) proteins have been reported to regulate type I IFN production during host antiviral innate immunity. The present study reported the zebrafish MARCH family member, MARCH7, as a negative regulator in virus-triggered type I IFN induction via targeting TANK-binding kinase 1 (TBK1) for degradation. As an IFN-stimulated gene (ISG), we discovered that MARCH7 was significantly induced by spring viremia of carp virus (SVCV) or poly(I:C) stimulation. Ectopic expression of MARCH7 reduced the activity of IFN promoter and dampened the cellular antiviral responses triggered by SVCV and grass carp reovirus (GCRV), which concomitantly accelerated the viral replication. Accordingly, the knockdown of MARCH7 by siRNA transfection significantly promoted the transcription of ISG genes and inhibited SVCV replication. Mechanistically, we found that MARCH7 interacted with TBK1 and degraded it via K48-linked ubiquitination. Further characterization of truncated mutants of MARCH7 and TBK1 confirmed that the C-terminal RING of MARCH7 is essential in the MARCH7-mediated degradation of TBK1 and the negative regulation of IFN antiviral response. This study reveals a molecular mechanism by which zebrafish MARCH7 negatively regulates the IFN response by targeting TBK1 for protein degradation, providing new insights into the essential role of MARCH7 in antiviral innate immunity.

Long Noncoding RNA AROD Inhibits Host Antiviral Innate Immunity via the miR-324-5p-CUEDC2 Axis.

Long noncoding RNAs (lncRNAs) are a class of noncoding RNAs that are involved in multiple biological processes. Here, we report a mechanism through which the lnc-AROD-miR-324-5p-CUEDC2 axis regulates the host innate immune response, using influenza A virus (IAV) as a model. We identified that host lnc-AROD without protein-coding capability is composed of 975 nucleotides. Moreover, lnc-AROD inhibited interferon-β expression, as well as interferon-stimulated genes ISG15 and MxA. Furthermore, in vivo assays confirmed that lnc-AROD overexpression increased flu virus pathogenicity and mortality in mice. Mechanistically, lnc-AROD interacted with miR-324-5p, leading to decreased binding of miR-324-5p to CUEDC2. Collectively, our findings demonstrated that lnc-AROD is a critical regulator of the host antiviral response via the miR-324-5p-CUEDC2 axis, and lnc-AROD functions as competing endogenous RNA. Our results also provided evidence that lnc-AROD serves as an inhibitor of the antiviral immune response and may represent a potential drug target. IMPORTANCE lnc-AROD is a potential diagnostic and discriminative biomarker for different cancers. However, so far the mechanisms of lnc-AROD regulating virus replication are not well understood. In this study, we identified that lnc-AROD is downregulated during RNA virus infection. We demonstrated that lnc-AROD enhanced CUEDC2 expression, which in turn inhibited innate immunity and favored IAV replication. Our studies indicated that lnc-AROD functions as a competing endogenous RNA that binds miR-324-5p and reduces its inhibitory effect on CUEDC2. Taken together, our findings reveal that lnc-AROD plays an important role during the host antiviral immune response.

Duck cGAS inhibits DNA and RNA virus replication by activating IFNs and antiviral ISGs.

Cyclic GMP-AMP Synthase (cGAS) is a pivotal adaptor of the signaling pathways involving the pattern recognition receptors and plays an important role in apoptosis and immune regulation. The cGAS function in mammals has been investigated extensively; however, the function of duck cGAS (du-cGAS) in response to viral infections is still unclear. This study aimed to clone the mallard (Anas platyrhynchos) cGAS homolog to investigate the function of duck cGAS (du-cGAS) in host antiviral innate immunity. The results showed that the open reading frame (ORF) region of the du-cGAS gene was 1296 bp, encoding 432 amino acids (aa) and exhibiting similar functional domains with its chicken counterpart. Knockdown of the endogenous du-cGAS by specific sgRNA strongly increased the replication of DNA viruses, including duck adenovirus B2 (DAdV B2) and duck short beak and dwarfism syndrome virus (SBDSV). However, the knockout did not impair the replication of novel duck reovirus (NDRV), an RNA virus. Furthermore, the mRNA expressions of type I interferon (IFNs) and vital interferon-stimulated genes (ISGs) were remarkably reduced in the du-cGAS knockout DEF cell line. Inversely, du-cGAS overexpression greatly activated the transcription of IFN-α, IFN-β, and vital ISGs, and impaired the replication of DAdV B2, SBDSV, and NDRV in the DEF cell line. Importantly, we found that a deletion of 68 aa in the N terminus didn't impair the antiviral function of du-cGAS. Overexpressing NTase Core, C-Domain (Mab21), or Zinc-Ribbon domain independently had no antiviral effects. Generally, these results reveal that du-cGAS is a vital component of the innate immune system of ducks, with a universal antiviral activity, and provides a useful strategy for the control of waterfowl viral diseases.

Flavivirus prM interacts with MDA5 and MAVS to inhibit RLR antiviral signaling

BackgroundVector-borne flaviviruses, including tick-borne encephalitis virus (TBEV), Zika virus (ZIKV), West Nile virus (WNV), yellow fever virus (YFV), dengue virus (DENV), and Japanese encephalitis virus (JEV), pose a growing threat to public health worldwide, and have evolved complex mechanisms to overcome host antiviral innate immunity. However, the underlying mechanisms of flavivirus structural proteins to evade host immune response remain elusive.ResultsWe showed that TBEV structural protein, pre-membrane (prM) protein, could inhibit type I interferon (IFN-I) production. Mechanically, TBEV prM interacted with both MDA5 and MAVS and interfered with the formation of MDA5-MAVS complex, thereby impeding the nuclear translocation and dimerization of IRF3 to inhibit RLR antiviral signaling. ZIKV and WNV prM was also demonstrated to interact with both MDA5 and MAVS, while dengue virus serotype 2 (DENV2) and YFV prM associated only with MDA5 or MAVS to suppress IFN-I production. In contrast, JEV prM could not suppress IFN-I production. Overexpression of TBEV and ZIKV prM significantly promoted the replication of TBEV and Sendai virus.ConclusionOur findings reveal the immune evasion mechanisms of flavivirus prM, which may contribute to understanding flavivirus pathogenicity, therapeutic intervention and vaccine development.

The game between host antiviral innate immunity and immune evasion strategies of senecavirus A - A cell biological perspective.

Innate immunity is the first line of the cellular host to defend against viral infection. Upon infection, viruses can be sensed by the cellular host's pattern recognition receptors (PRRs), leading to the activation of the signaling cascade and the robust production of interferons (IFNs) to restrict the infection and replication of the viruses. However, numerous cunning viruses have evolved strategies to evade host innate immunity. The senecavirus A (SVA) is a newly identified member of the Picornaviridae family, causing severe vesicular or ulcerative lesions on the oral mucosa, snout, coronary bands, and hooves of pigs of different ages. During SVA infection, the cellular host will launch the innate immune response and various physiological processes to restrict SVA. In contrast, SVA has evolved several strategies to evade the porcine innate immune responses. This review focus on the underlying mechanisms employed by SVA to evade pattern recognition receptor signaling pathways, type I interferon (IFN-α/β) receptor (IFNAR) signaling pathway, interferon-stimulated genes (ISGs) and autophagy, and stress granules. Deciphering the antiviral immune evasion mechanisms by SVA will enhance our understanding of SVA's pathogenesis and provide insights into developing antiviral strategies and improving vaccines.

CfIRF8-like interacts with the TBK1/IKKε family protein and regulates host antiviral innate immunity

The interferon regulatory factor (IRF) family, a class of transcription factors with key functions, are important in host innate immune defense and stress response. However, further research is required to determine the functions of IRFs in invertebrates. In this study, the coding sequence of an IRF gene was obtained from the Zhikong scallop (Chlamys farreri) and named CfIRF8-like. The open reading frame of CfIRF8-like was 1371 bp long and encoded 456 amino acids. Protein domain prediction revealed a typical IRF domain in the N-terminus of the CfIRF8-like protein and a typical IRF3 domain in the C-terminus. Multiple sequence alignment confirmed the conservation of the amino acid sequences of these two functional protein domains. Phylogenetic analysis showed that CfIRF8-like clustered with mollusk IRF8 proteins and then clustered with vertebrate IRF3, IRF4, and IRF5 subfamily proteins. Quantitative real-time PCR detected CfIRF8-like mRNA in all tested scallop tissues, with the highest expression in the gills. Simultaneously, the expression of CfIRF8-like transcripts in gills was significantly induced by polyinosinic–polycytidylic acid challenge. The results of protein interaction experiments showed that CfIRF8-like could directly bind the TBK1/IKKε family protein of scallop (CfIKK2) via its N-terminal IRF domain, revealing the presence of an ancient functional TBK1/IKKε-IRF signaling axis in scallops. Finally, dual-luciferase reporter assay results showed that the overexpression of CfIRF8-like in human embryonic kidney 293T cells could specifically activate the interferon β promoter of mammals and the interferon-stimulated response element promoter in dose-dependent manners. The findings of this preliminary analysis of the signal transduction and immune functions of scallop CfIRF8-like protein lay a foundation for an in-depth understanding of the innate immune function of invertebrate IRFs and the development of comparative immunology. The experimental results also provide theoretical support for the breeding of scallop disease-resistant strains.

Modulation of Host Antiviral Innate Immunity by African Swine Fever Virus: A Review.

African swine fever (ASF), caused by African swine fever virus (ASFV), is a highly contagious and fatal disease found in swine. However, the viral proteins and mechanisms responsible for immune evasion are poorly understood, which has severely hindered the development of vaccines. This review mainly focuses on studies involving the innate antiviral immune response of the host and summarizes the latest studies on ASFV genes involved in interferon (IFN) signaling and inflammatory responses. We analyzed the effects of candidate viral proteins on ASFV infection, replication and pathogenicity and identified potential molecular targets for novel ASFV vaccines. These efforts will contribute to the construction of novel vaccines and wonder therapeutics for ASF.