African Swine Fever Virus MGF360-12L Inhibits Type I Interferon Production by Blocking the Interaction of Importin α and NF-κB Signaling Pathway

Zhuo, Yisha; Guo, Zeheng; Ba, Tongtong; Zhang, Cheng; He, Lihua; Zeng, Cuiping; Dai, Hanchuan

doi:10.1007/s12250-020-00304-4

Cited by 73 publications

(65 citation statements)

References 46 publications

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“…pA238L inhibits TNF-a generation and expression. CBP/p300 is a histone acetyltransferase (HAT) that enables histone acetylation to promote transcription factor-mediated target (76) inhibit the interaction between p65 and importin a inhibit the interaction between NF-kB andnuclear transport proteins gene transcription. pA238L replaces the combination of cyclic AMP-responsive element/k3complex with CBP/p300 on the TNF-a promoter, inhibiting TNF-a activation.…”

Section: Tnf-a Inhibitionmentioning

confidence: 99%

“…Moreover, MGF360 and MGF505/530 inhibit the I-type IFN production and impact ( 14 ). ASFV MGF360-12L reduces IFN-β and NF-κB promoters activity and inhibits mRNA transcription of IFN-β, IRF3, STING, TBK1, ISG54, ISG56 and AP-1 ( 76 ).…”

Section: Asfv Immunomodulation Mechanismsmentioning

confidence: 99%

“…The interactions of MGF360-12L with KPNA2 (importin α2), KPNA3 (importin α3), and KPNA4 (importin α4) inhibit the interaction between p65 and importin α. Moreover, MGF360-12L inhibits the nuclear transport of NF-κB by inhibiting the interaction between NF-κB and nuclear transport proteins ( 76 ).…”

Section: Asfv Immunomodulation Mechanismsmentioning

confidence: 99%

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Structure of African Swine Fever Virus and Associated Molecular Mechanisms Underlying Infection and Immunosuppression: A Review

et al. 2021

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African swine fever (ASF) is an acute, highly contagious, and deadly infectious disease. The mortality rate of the most acute and acute ASF infection is almost 100%. The World Organization for Animal Health [Office International des épizooties (OIE)] lists it as a legally reported animal disease and China lists it as class I animal epidemic. Since the first diagnosed ASF case in China on August 3, 2018, it has caused huge economic losses to animal husbandry. ASF is caused by the African swine fever virus (ASFV), which is the only member of Asfarviridae family. ASFV is and the only insect-borne DNA virus belonging to the Nucleocytoplasmic Large DNA Viruses (NCLDV) family with an icosahedral structure and an envelope. Till date, there are still no effective vaccines or antiviral drugs for the prevention or treatment of ASF. The complex viral genome and its sophisticated ability to regulate the host immune response may be the reason for the difficulty in developing an effective vaccine. This review summarizes the recent findings on ASFV structure, the molecular mechanism of ASFV infection and immunosuppression, and ASFV-encoded proteins to provide comprehensive proteomic information for basic research on ASFV. In addition, it also analyzes the results of previous studies and speculations on the molecular mechanism of ASFV infection, which aids the study of the mechanism of clinical pathological phenomena, and provides a possible direction for an intensive study of ASFV infection mechanism. By summarizing the findings on molecular mechanism of ASFV- regulated host cell immune response, this review provides orientations and ideas for fundamental research on ASFV and provides a theoretical basis for the development of protective vaccines against ASFV.

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Section: Tnf-a Inhibitionmentioning

confidence: 99%

Section: Asfv Immunomodulation Mechanismsmentioning

confidence: 99%

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Structure of African Swine Fever Virus and Associated Molecular Mechanisms Underlying Infection and Immunosuppression: A Review

et al. 2021

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“…A previous study demonstrated that deletion of MGF360-12L led to upregulation of IFN-β and provided protective immunity against the challenge of virulent ASFV ( Reis et al, 2016 ), suggesting that MGF360-12L could be a potential IFN antagonist. To verify this hypothesis, Zhuo et al (2020) performed an in-depth study and found that MGF360-12L can suppress the transcription level and promoter activity of IFN-β and NF-κB. MGF360-12L could interact with nuclear transport proteins importin α (KPNA2, KPNA3, and KPNA4) at the nuclear localization signal domain to disrupt NF-κB nuclear translocation, resulting in the inhibition of type I IFN production.…”

Section: African Swine Fever Virus Immune Evasion Mechanisms and Their Relationship To Live Attenuated Vaccinesmentioning

confidence: 99%

Regulation and Evasion of Host Immune Response by African Swine Fever Virus

Yang

et al. 2021

Front. Microbiol.

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African swine fever (ASF) is an acute lethal hemorrhagic viral disease in domestic pigs and wild boars; is widely epidemic in Africa, Europe, Asia, and Latin America; and poses a huge threat to the pig industry worldwide. ASF is caused by the infection of the ASF virus (ASFV), a cytoplasmic double-stranded DNA virus belonging to the Asfarviridae family. Here, we review how the virus regulates the host immune response and its mechanisms at different levels, including interferon modulation, inflammation, apoptosis, antigen presentation, and cellular immunity.

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“…Additionally, multiple ASFV proteins, including A276R, A528R, I329L, DP96R, MGF-505-7R, and MGF360-12L, were shown to contribute to the inhibition of IFN production by targeting different pathways (14,(18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

African swine fever virus structural protein p17 inhibits cGAS-STING signaling pathway through interacting with STING

Zheng

Xia

Luo

et al. 2021

Preprint

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African swine fever (ASF) is highly contagious, causes high mortality in domestic and feral swine, and has a significant economic impact on the global swine industry due to the lack of a vaccine or an effective treatment. African swine fever virus (ASFV) encodes more than 150 polypeptides, which may have intricate and delicate interactions with the host for the benefit of the virus to evade the host’s defenses. However, currently, there is still a lack of information regarding the roles of the viral proteins in host cells. Here, our data demonstrated that the p17, encoded by D117L gene could suppress porcine cGAS-STING signaling pathway, exhibiting the inhibitions of TBK1 and IRF3 phosphorylations, downstream promoter activities, cellular mRNA transcriptions and ISG56 induction, and antiviral responses. Further, we found that p17 was located in endoplasmic reticulum (ER) and Golgi apparatus, and interacted with STING, perturbing it in the recruitment of TBK1 and IKKϵ Additionally, it appeared that the transmembrane domain (amino acids 39–59) of p17 could be required for interacting with STING and inhibiting cGAS-STING pathway. Taken together, p17 could inhibit the cGAS-STING pathway through its interaction with STING and interference with STING in the recruitment of TBK1 and IKKϵ

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African Swine Fever Virus MGF360-12L Inhibits Type I Interferon Production by Blocking the Interaction of Importin α and NF-κB Signaling Pathway

Cited by 73 publications

References 46 publications

Structure of African Swine Fever Virus and Associated Molecular Mechanisms Underlying Infection and Immunosuppression: A Review

Structure of African Swine Fever Virus and Associated Molecular Mechanisms Underlying Infection and Immunosuppression: A Review

Regulation and Evasion of Host Immune Response by African Swine Fever Virus

African swine fever virus structural protein p17 inhibits cGAS-STING signaling pathway through interacting with STING

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