2B and 3C Proteins of Senecavirus A Antagonize the Antiviral Activity of DDX21 via the Caspase-Dependent Degradation of DDX21

Zhao, Kuan; Guo, Xiaoran; Liu, Shuaifeng; Liu, Xiaona; Han, Ying; Wang, Lulu; Lei, Baishi; Zhang, Wu-Chao; Liu, Limin; Yuan, Wanzhe

doi:10.3389/fimmu.2022.951984

Cited by 14 publications

(13 citation statements)

References 39 publications

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“…The subcellular distribution of DDX21 into nucleolus is required for the RNA unwinding ( Song et al, 2017 ). DDX21 regulates viral replication through many ways, including inhibiting viral genome replication and prohibiting virus replication ( Watanabe et al, 2009 ; Abdullah et al, 2021 ; Li et al, 2022b ; Zhao et al, 2022 ). DDX21 interacts with rRNAs and snoRNAs to facilitate transcription and processing ( Flores-Rozas and Hurwitz, 1993 ).…”

Section: Discussionmentioning

confidence: 99%

“…DDX21 redistributes from the nucleus to the cytoplasm for inducing innate immune responses during dengue virus infection ( Dong et al, 2016 ). Moreover, DDX21 facilitates redistribution to the cytoplasm to reduce IFN-β production through disrupting the DDX1-DDX21-DHX36 complex during infection ( Li et al, 2022a ; Zhao et al, 2022 ). Herein, we demonstrated that DDX21 redistributed to the cytoplasm from the nucleolus during PCV2 infection ( Figure 1 ), suggesting that PCV2 infection induces DDX21 relocation to inhibit innate immunity and facilitate viral replication; however, the underlying mechanisms need further study.…”

Section: Discussionmentioning

confidence: 99%

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DEAD-box RNA helicase 21 interacts with porcine circovirus type 2 Cap protein and facilitates viral replication

Zhou,

Zhao,

Sun

et al. 2024

Front. Microbiol.

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Porcine circovirus type 2 (PCV2) is the etiological agent of PCV2-associated diseases that pose a serious threat to the swine industry. PCV2 capsid (Cap) protein has been shown to interact with DEAD-box RNA helicase 21 (DDX21), an important protein that regulates RNA virus replication. However, whether the interaction between DDX21 and the PCV2 Cap regulates PCV2 replication remains unclear. Herein, by using western blotting, interaction assays, and knockdown analysis, we found that PCV2 infection induced the cytoplasmic relocation of DDX21 from the nucleolus in cultured PK-15 cells. Moreover, the nuclear localization signal (NLS) of PCV2 Cap interacted directly with DDX21. The NLS of PCV2 Cap and 763GSRSNRFQNK772 residues at the C-terminal domain (CTD) of DDX21 were essential for the dual interaction. Upon shRNA-mediated DDX21 depletion in PK-15 cells, we observed impaired PCV2 replication via a lentivirus-delivered system, as evidenced by decreased levels of viral protein expression and virus production. In contrast, the replication of PCV2 increased in transiently DDX21-overexpressing cells. Our results indicate that DDX21 interacts with PCV2 Cap and plays a crucial role in virus replication. These results provide a reference for developing novel potential targets for prevention and control of PCV2 infection.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

DEAD-box RNA helicase 21 interacts with porcine circovirus type 2 Cap protein and facilitates viral replication

Zhou,

Zhao,

Sun

et al. 2024

Front. Microbiol.

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“…3389/fmicb.2023.1235620 Frontiers in Microbiology 07 frontiersin.org system attacks (Qian et al, 2017;Xue et al, 2018a,b;Wen et al, 2019). Additionally, SVV 3C pro affects various processes, such as cell mRNA translation (Xue et al, 2020;Song et al, 2021Song et al, , 2022bWen et al, 2022;Zhao et al, 2022), Pyroptosis (Wen et al, 2021a), apoptosis (Liu et al, 2019;Zhao et al, 2023), and autophagy (Wen et al, 2021b;Zhao et al, 2023), which may facilitate virus replication. Notably, this protease interacts with many crucial host proteins, cleaving them to exploit host cell resources while avoiding or mitigating immune responses (Table 1).…”

Section: Discussionmentioning

confidence: 99%

“…DDX21 mediates innate immunity and regulates the viral replication of viruses such as foot-and-mouth disease virus (FMDV) (Abdullah et al, 2021), dengue virus (DENV) (Dong et al, 2016) and Borna disease virus (BDV) (Watanabe et al, 2009). Furthermore, DDX21 has been shown to inhibit SVV replication, but its effects can be weakened by SVV 3C pro , which induces caspase-dependent degradation of DDX21 and suppresses host antiviral immunity, limiting the cell antiviral response (Zhao et al, 2022). DHX30, a DEAD family member, contributes to the biosynthesis of mitochondrial ribosomes.…”

Section: Role Of 3c Proteases In Regulating Mrnamentioning

confidence: 99%

Seneca Valley virus 3Cpro antagonizes host innate immune responses and programmed cell death

Zhang,

Li,

Huang

et al. 2023

Front. Microbiol.

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Seneca Valley virus (SVV), a member of the Picornaviridae family, may cause serious water blister diseases in pregnant sows and acute death in newborn piglets, which have resulted in economic losses in pig production. The 3C protease is a vital enzyme for SVV maturation and is capable of regulating protein cleavage and RNA replication of the virus. Additionally, this protease can impede the host’s innate immune response by targeting the interferon pathway’s principal factor and enhance virus replication by modulating the host’s RNA metabolism while simultaneously triggering programmed cell death. This article reviews recent studies on SVV 3C functions, which include viral replication promotion, cell apoptosis modulation and host immune response evasion, and provides a theoretical basis for research on preventing and controlling SVV infection.

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“…The mutated 3C failed to induce the degradation of DDX21. All of these suggested that the protease activity of 3C protein was necessary for the degradation of DDX21, which contributed to SVA evading the antiviral effect of DDX21 ( 67 ).…”

Section: Ddx21mentioning

confidence: 99%

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

et al. 2022

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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.

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2B and 3C Proteins of Senecavirus A Antagonize the Antiviral Activity of DDX21 via the Caspase-Dependent Degradation of DDX21

Cited by 14 publications

References 39 publications

DEAD-box RNA helicase 21 interacts with porcine circovirus type 2 Cap protein and facilitates viral replication

DEAD-box RNA helicase 21 interacts with porcine circovirus type 2 Cap protein and facilitates viral replication

Seneca Valley virus 3Cpro antagonizes host innate immune responses and programmed cell death

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

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