Spring viraemia of carp virus induces autophagy for necessary viral replication

Liu, Liyue; Zhu, Bibo; Wu, Shusheng; Li, Lin; Liu, Guangxin; Zhou, Yang; Wang, Weimin; Asim, Muhammad; Yuan, Junfa; Li, Lijuan; Wang, Min; Lu, Yuanan; Wang, Huanling; Cao, Jianbo; Liu, Xueqin

doi:10.1111/cmi.12387

Cited by 88 publications

(61 citation statements)

References 33 publications

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“…Previous studies demonstrated that SVCV induced the autophagy of host cells and upregulated the expression of related genes (23). In the current study, the N protein inhibited IFN expression by degrading MAVS, which provided another strategy for SVCV to resist the host defense system.…”

Section: Discussionmentioning

confidence: 51%

“…For example, by using high-throughput methods such as pathway-targeted microarrays and transcriptomic and proteomic analyses, many immune-and autophagy-related genes have been identified to be involved in an SVCV infection (22)(23)(24)(25). The expression of IFN could be elicited by an SVCV infection, and overexpression of IFN could significantly increase the survival of zebrafish embryos infected with SVCV (26)(27)(28).…”

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confidence: 99%

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Spring Viremia of Carp Virus N Protein Suppresses Fish IFNφ1 Production by Targeting the Mitochondrial Antiviral Signaling Protein

et al. 2016

The Journal of Immunology

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For a virus to replicate efficiently, it must try and inhibit host IFN expression because IFN is an important host defense at early stages after viral infection. For aquatic viruses, the mechanisms used to escape the hosts IFN system are still unclear. In this study, we show that the N protein of spring viremia of carp virus (SVCV) inhibits zebrafish IFNφ1 production by degrading the mitochondrial antiviral signaling protein (MAVS). First, the upregulation of IFNφ1 promoter activity stimulated by polyinosinic:polycytidylic acid, retinoic acid–inducible gene I (RIG-I) or MAVS was suppressed by the SVCV infection. However, the upregulation by the downstream factor of the RIG-I–like receptor signaling pathway, TANK-binding kinase 1, was not affected. Notably, at the protein level, MAVS decreased remarkably when cells were infected with SVCV. Second, consistent with the result of the SVCV infection, overexpression of the N protein of SVCV blocked the IFNφ1 transcription activated by MAVS and downregulated MAVS expression at the protein level but not at the mRNA level. Further analysis demonstrated that the N protein targeted MAVS for K48-linked ubiquitination, which promoted the degradation of MAVS. These data indicated that fish MAVS could be degraded by the N protein of SVCV through the ubiquitin-proteasome pathway. To our knowledge, this is the first article of a fish RIG-I–like receptor pathway interfered by an aquatic virus in an ubiquitin-proteasome manner, suggesting that immune evasion of a virus also exists in lower vertebrates.

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Section: Discussionmentioning

confidence: 51%

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confidence: 99%

Spring Viremia of Carp Virus N Protein Suppresses Fish IFNφ1 Production by Targeting the Mitochondrial Antiviral Signaling Protein

et al. 2016

The Journal of Immunology

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“…However, effective treatment for SVCV infection has presently been very limited and this might partially be due to currently poor understanding of the viral pathogenic mechanism; no vaccine against SVCV is currently available [16]. Therefore, improved understanding of host immune responses to viral infection may facilitate the discovery of novel targets to control SVCV infection and replication in carp and other fish species.…”

Section: Introductionmentioning

confidence: 99%

Molecular Characterization, Tissue Distribution and Expression, and Potential Antiviral Effects of TRIM32 in the Common Carp (Cyprinus carpio)

Wang

et al. 2016

IJMS

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Tripartite motif-containing protein 32 (TRIM32) belongs to the tripartite motif (TRIM) family, which consists of a large number of proteins containing a RING (Really Interesting New Gene) domain, one or two B-box domains, and coiled coil motif followed by different C-terminal domains. The TRIM family is known to be implicated in multiple cellular functions, including antiviral activity. However, it is presently unknown whether TRIM32 of common carp (Cyprinus carpio) has the antiviral effect. In this study, the sequence, expression, and antiviral function of TRIM32 homolog from common carp were analyzed. The full-length coding sequence region of trim32 was cloned from common carp. The results showed that the expression of TRIM32 (mRNA) was highest in the brain, remained stably expressed during embryonic development, and significantly increased following spring viraemia of carp virus (SVCV) infection. Transient overexpression of TRIM32 in affected Epithelioma papulosum cyprinid cells led to significant decrease of SVCV production as compared to the control group. These results suggested a potentially important role of common carp TRIM32 in enhancing host immune response during SVCV infection both in vivo and in vitro.

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“…For example, SVCV G protein forms the trimeric spikes on the viral outer surface to mediate endocytosis. In addition, G protein also induces autophagy in infected cells, which is beneficial for SVCV proliferation (32). The N protein associates with viral RNA, providing a helical symmetry to the viral nucleocapsid.…”

Section: Discussionmentioning

confidence: 99%

The P Protein of Spring Viremia of Carp Virus Negatively Regulates the Fish Interferon Response by Inhibiting the Kinase Activity of TANK-Binding Kinase 1

Wang

et al. 2016

J Virol

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Spring viremia of carp virus (SVCV) is an efficient pathogen causing high mortality in the common carp. Fish interferon (IFN) is a powerful cytokine enabling host cells to establish an antiviral response; therefore, the strategies that SVCV uses to avoid the cellular IFN response were investigated. Here, we report that the SVCV P protein is phosphorylated by cellular TANK-binding kinase 1 (TBK1), which decreases IFN regulatory factor 3 (IRF3) phosphorylation and suppresses IFN production. First, overexpression of P protein inhibited the IFN promoter activation induced by SVCV and the IFN activity activated by the mitochondrial antiviral signaling protein (MAVS) although TBK1 activity was not blocked by P protein. Second, P protein colocalized and interacted with TBK1. Dominant negative experiments suggested that the TBK1 N-terminal kinase domain interacted with P protein and was essential for P protein and IRF3 phosphorylation. Finally, P protein overexpression reduced the IRF3 phosphorylation activated by TBK1 and reduced host cellular ifn transcription. Collectively, our data demonstrated that the SVCV P protein is a decoy substrate for the host phosphokinase TBK1, preventing IFN production and facilitating SVCV replication. IMPORTANCETBK1 is a pivotal phosphokinase that activates host IFN production to defend against viral infection; thus, it is a potential target for viruses to negatively regulate IFN response and facilitate viral evasion. We report that the SVCV P protein functions as a decoy substrate for cellular TBK1, leading to the reduction of IRF3 phosphorylation and suppression of IFN expression. These findings reveal a novel immune evasion mechanism of SVCV. In aquatic viruses, spring viremia of carp virus (SVCV) belongs to the genus Vesiculovirus of the family Rhabdoviridae and causes significant mortality in the common carp (Cyprinus carpio) (1). Regarding its genome structure, SVCV encodes an ϳ11-kb negative-sense, single-stranded RNA that encodes five proteins in the following order (3= to 5=): nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G), and viral RNA-dependent RNA polymerase (L) (2-4). The roles of these proteins in the replication and proliferation of rhabdovirus have been explored. N protein associates with viral RNA to form the nucleocapsid during viral assembly. M protein participates in the assembly and budding of virus, and G protein is involved in viral endocytosis. Moreover, as a phosphoprotein, the P protein is involved in several viral replication and assembly processes. As an example, the functional phosphorylated P protein interacts with the L protein to form a viral polymerase complex that interacts with the RNA template. In addition, the P protein also maintains the N protein in a soluble, encapsidation-competent form (1, 5).In host cells, viral RNAs can be recognized by the cellular immune system, triggering an antiviral response (6). In the cytoplasm, RIG-I-like receptors (RLRs), including RIG-I and MDA5, are the major pattern-recognition...

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Spring viraemia of carp virus induces autophagy for necessary viral replication

Cited by 88 publications

References 33 publications

Spring Viremia of Carp Virus N Protein Suppresses Fish IFNφ1 Production by Targeting the Mitochondrial Antiviral Signaling Protein

Spring Viremia of Carp Virus N Protein Suppresses Fish IFNφ1 Production by Targeting the Mitochondrial Antiviral Signaling Protein

Molecular Characterization, Tissue Distribution and Expression, and Potential Antiviral Effects of TRIM32 in the Common Carp (Cyprinus carpio)

The P Protein of Spring Viremia of Carp Virus Negatively Regulates the Fish Interferon Response by Inhibiting the Kinase Activity of TANK-Binding Kinase 1

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