Infectious bronchitis virus nucleocapsid protein suppressed type I interferon production by interfering with the binding of MDA5-dsRNA and interacting with LGP2

Huang, Mengjiao; Liu, Yuan; Xia, Yongbo; Wang, Jingjing; Zheng, Xuewei; Cao, Yongchang

doi:10.1016/j.vetmic.2023.109798

Cited by 8 publications

(4 citation statements)

References 56 publications

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“…Besides ORF1a, amino acid mutations were also identified in the S, 3a, E, N, and ORFX proteins in this study. Previous research has shown the involvement of S, 3a, E, and N proteins as virulence genes in regulating IBV pathogenicity [ 19 , 20 , 35 , 36 ]. However, the role of ORFX in viral pathogenicity remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Deciphering the Genetic Variation: A Comparative Analysis of Parental and Attenuated Strains of the QXL87 Vaccine for Infectious Bronchitis

Wang,

Bo,

Zhang

et al. 2024

Animals

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The QXL87 live attenuated vaccine strain for infectious bronchitis represents the first approved QX type (GI-19 lineage) vaccine in China. This strain was derived from the parental strain CK/CH/JS/2010/12 through continuous passage in SPF chicken embryos. To elucidate the molecular mechanism behind its attenuation, whole-genome sequencing was conducted on both the parental and attenuated strains. Analysis revealed 145 nucleotide mutations in the attenuated strain, leading to 48 amino acid mutations in various proteins, including Nsp2 (26), Nsp3 (14), Nsp4 (1), S (4), 3a (1), E (1), and N (1). Additionally, a frameshift mutation caused by a single base insertion in the ORFX resulted in a six-amino-acid extension. Subsequent comparison of post-translational modification sites, protein structure, and protein–protein binding sites between the parental and attenuated strains identified three potential virulence genes: Nsp2, Nsp3, and S. The amino acid mutations in these proteins not only altered their conformation but also affected the distribution of post-translational modification sites and protein–protein interaction sites. Furthermore, three potential functional mutation sites—P106S, A352T, and L472F, all located in the Nsp2 protein—were identified through PROVEAN, PolyPhen, and I-Mutant. Overall, our findings suggest that Nsp2, Nsp3, and S proteins may play a role in modulating IBV pathogenicity, with a particular focus on the significance of the Nsp2 protein. This study contributes to our understanding of the molecular mechanisms underlying IBV attenuation and holds promise for the development of safer live attenuated IBV vaccines using reverse genetic approaches.

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Section: Discussionmentioning

confidence: 99%

Deciphering the Genetic Variation: A Comparative Analysis of Parental and Attenuated Strains of the QXL87 Vaccine for Infectious Bronchitis

Wang,

Bo,

Zhang

et al. 2024

Animals

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“…However, IBV has developed multiple methods to evade the host’s innate immune response [ 36 ]. The structural nucleocapsid (N) protein of IBV can suppress type I IFN production by interfering with the binding of melanoma differentiation-associated gene 5(MDA5)-dsRNA [ 37 ]; IBV nsp14 inhibits the JAK/STAT signaling pathway by degrading JAK1 in chicken macrophage cells [ 38 ]; The nsp15 of IBV supports virus replication by interfering with the formation of antiviral stress granules (SGs) through antagonizing the activation of PKR and regulating the accumulation of viral dsRNA [ 39 ]. In this study, we demonstrated that a proteolytically defective fragment of the PL1pro protein, which IBV codes, plays a significant role in providing resistance to the host’s innate immune response.…”

Section: Discussionmentioning

confidence: 99%

The role of IBV PL1pro in virus replication and suppression of host innate immune responses

Liu,

Mu,

Jia

et al. 2023

BMC Vet Res

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Background Coronavirus papain-like proteases (PLpros) play a crucial role in virus replication and the evasion of the host immune response. Infectious bronchitis virus (IBV) encodes a proteolytically defective remnant of PL1pro and an active PL2pro. However, the function of PL1pro in IBV remains largely unknown. This study aims to explore the effect of PL1pro on virus replication and underlying mechanisms. Results The recombinant viruses rIBV-ΔPL1pro and rIBV-ΔPL1pro-N were obtained using reverse genetic techniques through the deletion of the IBV PL1pro domain and the N-terminal conserved sequence of PL1pro (PL1pro-N). We observed significantly lower replication of rIBV-ΔPL1pro and rIBV-ΔPL1pro-N than wild-type IBV. Further investigation revealed that the lack of PL1pro-N in IBV decreased virus resistance to interferon (IFN) while also inducing host immune response by enhancing the production of IFN-β and activating the downstream STAT1 signaling pathway of IFNs. In addition, the overexpression of PL1pro-N significantly suppressed type I IFN response by down-regulating the expressions of genes in the IFN pathway. Conclusions Our data demonstrated that IBV PL1pro plays a crucial role in IBV replication and the suppression of host innate immune responses, suggesting that IBV PL1pro could serve as a promising molecular target for antiviral therapy.

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“…Studies have found that once IBV infects the body, the host initiates the acquired immune response driven in large part by IFNs. Treatment of IBV-infected cells or animal models with type I IFNs can inhibit viral replication [20]. Therefore, we speculated that the inhibitory effect of Baicalin on viral replication may be related to its regulation of the type I IFN response.…”

Section: Effect Of Baicalin On Mrna Levels Of Ifn-α and Ifn-β In Vitromentioning

confidence: 99%

Antiviral Activity of Baicalin Against Infectious Bronchitis Virus

He,

Wang,

Guo

et al. 2024

Preprint

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Background Baicalin, the main metabolic component of Scutellaria Baicalin Georgi, displays potent anti-inflammatory, anti-oxidant, anti-apoptotic, anti-bactericidal, and antiviral properties. Baicalin was found to be effective in the treatment of infectious bronchitis (IB) in chickens. However, the molecular mechanism of treatment remained unclear. Therefore, in this study, the antiviral activities of baicalin on infectious bronchitis virus (IBV) were evaluated in vitro and in vivo for the first time, to explore the molecular mechanism of baicalin inhibiting IBV replication. Results Treatment with 20 µg/mL baicalin significantly reduced relative mRNA expression and IBV viral titers, a finding confirmed by immunofluorescence studies in chicken embryo kidney (CEK) cells. Baicalin treatment at a dose of 45 mg/kg significantly reduced IBV induced injury in the trachea, lung and kidney. Baicalin treatment also led to an upregulation of both interferon-α (IFN-α) and Interferon-β (IFN-β), with IFN-β increased the most. Although treatment with baicalin did not influence the mRNA expression of melanoma differentiation associated gene 5 (MDA5), Toll-like receptor 3 (TLR3), and Toll-like receptor 9 (TLR9), mRNA levels of mitochondrial antiviral signaling gene (MAVS), TANK binding kinase 1 (TBK1), and Interferon regulatory factor 7 (IRF7) increased, with MAVS showing the largest increase amongst all cytokines measured in vitro. Overexpression of MAVS significantly upregulated the expression of IFN-β and reduced the viral titer of IBV. Knockdown of MAVS significantly affected the antiviral effect of baicalin on IBV. Conclusions Baicalin possesses significant anti-IBV effects in vitro and in vivo. Baicalin-induced increases in the expression of type I interferons in CEK cells after IBV infection is likely linked to increased signaling through the enhanced MAVS expression in the MDA5 pathway. Baicalin’s inhibition of IBV replication was also closely related to MAVS cytokines, but not dependent on MAVS expression. These findings are important to accelerate our understanding of the antiviral effects of baicalin and provide new insights into the development of effective therapeutic strategies.

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Infectious bronchitis virus nucleocapsid protein suppressed type I interferon production by interfering with the binding of MDA5-dsRNA and interacting with LGP2

Cited by 8 publications

References 56 publications

Deciphering the Genetic Variation: A Comparative Analysis of Parental and Attenuated Strains of the QXL87 Vaccine for Infectious Bronchitis

Deciphering the Genetic Variation: A Comparative Analysis of Parental and Attenuated Strains of the QXL87 Vaccine for Infectious Bronchitis

The role of IBV PL1pro in virus replication and suppression of host innate immune responses

Antiviral Activity of Baicalin Against Infectious Bronchitis Virus

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