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

Zheng, Wanglong; Xia, Nengwen; Zhang, Jiajia; Cao, Qi; Jiang, Sheng; Luo, Jia; Wang, Hui; Chen, Nanhua; Zhang, Quan; Meurens, François; Zhu, Jianzhong

doi:10.3389/fimmu.2022.941579

Cited by 26 publications

(21 citation statements)

References 47 publications

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“…However, ASFV-encoded pE184L can prevent the formation of “STING-IRF3-TBK1” complex by impairing the oligomerization and dimerization of STING [ 43 ]. ASFV structural protein p17 can also disrupt the recruitment of TBK1 and Ikkε by interacting with STING as well although its implications on STING are not clearly elucidated [ 44 ]. Secondly, TBK1, a crucial kinase, is required for the IRF3 phosphorylation [ 45 ].…”

Section: Suppression Of Ifn-i Production and Ifn-induced Antiviral Re...mentioning

confidence: 99%

Antagonisms of ASFV towards Host Defense Mechanisms: Knowledge Gaps in Viral Immune Evasion and Pathogenesis

Zhu

Deng³

et al. 2023

Viruses

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African swine fever (ASF) causes high morbidity and mortality of both domestic pigs and wild boars and severely impacts the swine industry worldwide. ASF virus (ASFV), the etiologic agent of ASF epidemics, mainly infects myeloid cells in swine mononuclear phagocyte system (MPS), including blood-circulating monocytes, tissue-resident macrophages, and dendritic cells (DCs). Since their significant roles in bridging host innate and adaptive immunity, these cells provide ASFV with favorable targets to manipulate and block their antiviral activities, leading to immune escape and immunosuppression. To date, vaccines are still being regarded as the most promising measure to prevent and control ASF outbreaks. However, ASF vaccine development is delayed and limited by existing knowledge gaps in viral immune evasion, pathogenesis, etc. Recent studies have revealed that ASFV can employ diverse strategies to interrupt the host defense mechanisms via abundant self-encoded proteins. Thus, this review mainly focuses on the antagonisms of ASFV-encoded proteins towards IFN-I production, IFN-induced antiviral response, NLRP3 inflammasome activation, and GSDMD-mediated pyroptosis. Additionally, we also make a brief discussion concerning the potential challenges in future development of ASF vaccine.

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Section: Suppression Of Ifn-i Production and Ifn-induced Antiviral Re...mentioning

confidence: 99%

Antagonisms of ASFV towards Host Defense Mechanisms: Knowledge Gaps in Viral Immune Evasion and Pathogenesis

Zhu

Deng³

et al. 2023

Viruses

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“…In this regard, our group described that the cGAS/STING pathway is only efficiently controlled by virulent ASFV strains, while attenuated ASFV strain infection leads to IFN-β production [11]. Subsequent studies have reinforced this finding, identifying a multitude of viral factors that control some of the elements of the cGAS/STING pathway [12][13][14][15][16][17][18][19]. The type I IFN-induced JAK/STAT pathway has also been described as being controlled by ASFV [20], further relating type I IFN to virulence.…”

Section: Introductionmentioning

confidence: 99%

Deletion of MGF505-2R Gene Activates the cGAS-STING Pathway Leading to Attenuation and Protection against Virulent African Swine Fever Virus

Sunwoo,

García-Belmonte,

Walczak

et al. 2024

Vaccines

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African swine fever virus (ASFV) is the etiological agent causing African swine fever (ASF), affecting domestic pigs and wild boar, which is currently the biggest animal epidemic in the world and a major threat to the swine sector. At present, some safety concerns about using LAVs against ASFV still exist despite a commercial vaccine licensed in Vietnam. Therefore, the efforts to identify virulence factors and their mechanisms, as well as to generate new vaccine prototypes, are of major interest. In this work, we have identified the MGF505-2R gene product as an inhibitor of the cGAS/STING pathway, specifically through its interaction with STING protein, controlling IFN-β production. In addition, immunization of a recombinant virus lacking this gene, Arm/07-ΔMGF505-2R, resulted in complete attenuation, demonstrating its involvement in ASFV virulence. Finally, immunization with Arm/07-ΔMGF505-2R induced the generation of antibodies and proved to be partially protective against virulent ASFV strains. These results identify MGF505-2R, as well as its mechanism of action, as a gene contributing to understanding the molecular mechanisms of ASFV virulence, which will be of great value in the design of future vaccine prototypes.

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“…D117L/p17 a minor capsid protein that is also a component of the internal envelope [34] -is also essential for virus morphogenesis [43]. D117L/p17 is immunogenic [44] and may have immunomodulatory abilities [45]. B438L/p49 is required for the assembly of icosahedral virions and is located at the vertices of the capsid [35,46].…”

Section: Introductionmentioning

confidence: 99%

Capsid Specific Antibody Responses of Domestic Pigs Immunized with Low Virulent African Swine Fever Virus

Tng¹,

Al-Adwani²,

Pauletto³

et al. 2023

Preprint

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African swine fever (ASF) is a lethal disease in pigs that has grave socio-economic implications worldwide. For the development of vaccines against African swine fever virus (ASFV), immunogenic antigens that generate protective immune responses need to be identified. There are over 150 viral proteins - many of which are uncharacterized – and humoral immunity to ASFV has not been closely examined. To profile antigen specific antibody responses, we developed luciferase-linked antibody capture assays (LACAs) for a panel of ASFV capsid proteins and screened sera from inbred and outbred animals that were previously immunized with low virulent ASFV before challenge with virulent ASFV. Antibodies to B646L/p72, D117L/p17, M1249L and E120R/p14.5 were detected in this study; however, we were unable to detect B438L specific antibodies. Although OURT88/1 induced viremia was observed in the presence of anti-B646L/p72 antibodies as well as B602L antibodies they were associated with recovery from lethal disease in inbred and outbred animals. However, these antibodies did not correlate with protection against Georgia 2007/1 infection. Antibody responses against M1249L and E120R/p14.5 were observed in animals with reduced clinical signs and viremia. Here we present LACAs as a tool for targeted profiling of antigen specific antibody responses to inform vaccine development.

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

Cited by 26 publications

References 47 publications

Antagonisms of ASFV towards Host Defense Mechanisms: Knowledge Gaps in Viral Immune Evasion and Pathogenesis

Antagonisms of ASFV towards Host Defense Mechanisms: Knowledge Gaps in Viral Immune Evasion and Pathogenesis

Deletion of MGF505-2R Gene Activates the cGAS-STING Pathway Leading to Attenuation and Protection against Virulent African Swine Fever Virus

Capsid Specific Antibody Responses of Domestic Pigs Immunized with Low Virulent African Swine Fever Virus

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