MGF360-9L Is a Major Virulence Factor Associated with the African Swine Fever Virus by Antagonizing the JAK/STAT Signaling Pathway

Zhang, Ke-Shan; Yang, Bo; Shen, Chao; Zhang, Ting; Hao, Yu; Zhang, Dajun; Liu, Huanan; Shi, Xijuan; Li, Guoli; Yang, Jinke; Zheng, Haixue; Zhu, Zixiang; Tian, Hong; Yang, Fan; Ru, Yi; Cao, Wei; Guo, Jianpeng; He, Jijun; Liu, Xiangtao

doi:10.1128/mbio.02330-21

Cited by 76 publications

(54 citation statements)

References 47 publications

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“…The virulent 22653/14 strain seemed to have developed mechanisms to suppress the induction of several type I IFN genes (10).The highly virulent strain Lisboa60 could inhibit IFN production in macrophages using a way independent on IRF3 modulation (11). Additionally, multiple ASFV proteins were shown to contribute to the inhibition of type I IFN responses by targeting various innate immune pathways, such as the cGAS-STING pathway, Toll-like receptors pathway, JAK/STAT pathway and NF-kB pathway (12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

African Swine Fever Virus Structural Protein p17 Inhibits cGAS-STING Signaling Pathway Through Interacting With STING

et al. 2022

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African swine fever virus (ASFV) encodes more than 150 proteins, which establish complex interactions with the host for the benefit of the virus in order 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 ASFV structural protein p17 exerts a negative regulatory effect on cGAS-STING signaling pathway and the STING signaling dependent anti-HSV1 and anti-VSV functions. Further, the results indicated that ASFV p17 was located in ER and Golgi apparatus, and interacted with STING. ASFV p17 could interfere the STING to recruit TBK1 and IKKϵ through its interaction with STING. It was also suggested that the transmembrane domain (amino acids 39–59) of p17 is required for interacting with STING and inhibiting cGAS-STING pathway. Additionally, with the p17 specific siRNA, the ASFV induced IFN-β, ISG15, ISG56, IL-6 and IL-8 gene transcriptions were upregulated in ASFV infected primary porcine alveolar macrophages (PAMs). Taken together, ASFV p17 can inhibit the cGAS-STING pathway through its interaction with STING and interference of the recruitment of TBK1 and IKKϵ. Our work establishes the role of p17 in the immune evasion and thus provides insights on ASFV pathogenesis.

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Section: Introductionmentioning

confidence: 99%

African Swine Fever Virus Structural Protein p17 Inhibits cGAS-STING Signaling Pathway Through Interacting With STING

et al. 2022

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“…Another gene involved in disease production is MGF360-9L [ 42 ]. It was shown that the MGF360-9L gene is involved in the down-regulation of interferon expression.…”

Section: Identification Of Novel Determinants Of Virulence In the Asf...mentioning

confidence: 99%

Recombinant ASF Live Attenuated Virus Strains as Experimental Vaccine Candidates

Gladue

2022

Viruses

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African swine fever (ASF) is causing a pandemic affecting swine in a large geographical area of the Eastern Hemisphere, from Central Europe to East and Southeast Asia, and recently in the Americas, the Dominican Republic and Haiti. The etiological agent, ASF virus (ASFV), infects both domestic and wild swine and produces a variety of clinical presentations depending on the virus strain and the genetics of the pigs infected. No commercial vaccines are currently available, although experimental recombinant live attenuated vaccine candidates have been shown to be efficacious in protecting animals against disease when challenged with homologous virulent strains. This review attempts to systematically provide an overview of all the live attenuated strains that have been shown to be experimental vaccine candidates. Moreover, it aims to analyze the development of these vaccine candidates, obtained by deleting specific genes or group of genes, and their efficacy in preventing virus infection and clinical disease after being challenged with virulent isolates. This report summarizes all the experimental vaccine strains that have shown promise against the contemporary pandemic strain of African swine fever.

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“…For instance, TBK1 is inhibited (or degraded) by E120R ( Liu H. et al, 2021 ), DP96R ( Wang et al, 2018 ), MGF-360-11L ( Yang et al, 2022 ), and A137R ( Sun et al, 2022 ). Similarly, JAK/STAT are targeted by MGF-360-9L ( Zhang et al, 2022 ) and MGF-505-7R ( Li et al, 2021b ). Some ASFV proteins, like I226R ( Hong et al, 2022 ), I329L ( de Oliveira et al, 2011 ), and MGF-360-12L ( Zhuo et al, 2021 ) are able to target both the IFN and NF-κB pathways at the same time.…”

Section: Viral Antagonism Of Interferon and Nuclear Factor κB Pathway...mentioning

confidence: 99%

New Insights in the Interplay Between African Swine Fever Virus and Innate Immunity and Its Impact on Viral Pathogenicity

et al. 2022

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The continuous spread of African swine fever virus (ASFV) in Europe and Asia represents a major threat to livestock health, with billions of dollars of income losses and major perturbations of the global pig industry. One striking feature of African swine fever (ASF) is the existence of different forms of the disease, ranging from acute with mortality rates approaching 100% to chronic, with mild clinical manifestations. These differences in pathogenicity have been linked to genomic alterations present in attenuated ASFV strains (and absent in virulent ones) and differences in the immune response of infected animals. In this mini-review, we summarized current knowledge on the connection between ASFV pathogenicity and the innate immune response induced in infected hosts, with a particular focus on the pathways involved in ASFV detection. Indeed, recent studies have highlighted the key role of the DNA sensor cGAS in ASFV sensing. We discussed what other pathways may be involved in ASFV sensing and inflammasome activation and summarized recent findings on the viral ASFV genes involved in the modulation of the interferon (IFN) and nuclear factor kappa B (NF-κB) pathways.

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MGF360-9L Is a Major Virulence Factor Associated with the African Swine Fever Virus by Antagonizing the JAK/STAT Signaling Pathway

Cited by 76 publications

References 47 publications

African Swine Fever Virus Structural Protein p17 Inhibits cGAS-STING Signaling Pathway Through Interacting With STING

African Swine Fever Virus Structural Protein p17 Inhibits cGAS-STING Signaling Pathway Through Interacting With STING

Recombinant ASF Live Attenuated Virus Strains as Experimental Vaccine Candidates

New Insights in the Interplay Between African Swine Fever Virus and Innate Immunity and Its Impact on Viral Pathogenicity

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