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

Wang, Yue; Kang, Weifang; Yang, Wei; Zhang, Jing; Li, Dan; Zheng, Haixue

doi:10.3389/fimmu.2021.715582

Cited by 90 publications

(87 citation statements)

References 90 publications

(240 reference statements)

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“…On the contrary, viruses have developed multiple strategies to resist host immune defenses, and counteract IFN signaling. ASFV encodes more than 150 polypeptides, which establish complex interactions with the host for the benefit of the virus in order to evade the host's defenses (1). However, currently, there is still a lack of information regarding the roles of the viral proteins in host cells.…”

Section: Discussionmentioning

confidence: 99%

“…African swine fever virus (ASFV), the causative agent of African swine fever (ASF) which is a contagious disease of domestic pigs and wild boar, has spread globally in recent years with serious economic consequences for the swine industry. ASFV contains a linear double-stranded DNA genome that varies in length from about 170 to 193 kb and encodes 150-200 viral proteins, including 68 structural proteins and more than 100 non-structural proteins (1). Monocyte-macrophages are the main target cells of ASFV (2).…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

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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“…ASFV infection has been shown to upregulate the expression of immunosuppressive cytokines to put a strain on the host immune response. Previous studies have shown that IL27 , a suppressor of the immune response of Th1 and Th17 cells, is downregulated during ASFV infection [ 127 ]. However, IL27 was significantly upregulated in our study by over 2-fold in the medium and high dose groups.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome profile of spleen tissues from locally-adapted Kenyan pigs (Sus scrofa) experimentally infected with three varying doses of a highly virulent African swine fever virus genotype IX isolate: Ken12/busia.1 (ken-1033)

et al. 2022

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Background African swine fever (ASF) is a lethal hemorrhagic disease affecting domestic pigs resulting in up to 100% mortality rates caused by the ASF virus (ASFV). The locally-adapted pigs in South-western Kenya have been reported to be resilient to disease and harsh climatic conditions and tolerate ASF; however, the mechanisms by which this tolerance is sustained remain largely unknown. We evaluated the gene expression patterns in spleen tissues of these locally-adapted pigs in response to varying infective doses of ASFV to elucidate the virus-host interaction dynamics. Methods Locally adapted pigs (n = 14) were experimentally infected with a high dose (1x106HAD50), medium dose (1x104HAD50), and low dose (1x102HAD50) of the highly virulent genotype IX ASFV Ken12/busia.1 (Ken-1033) isolate diluted in PBS and followed through the course of infection for 29 days. The in vivo pig host and ASFV pathogen gene expression in spleen tissues from 10 pigs (including three from each infective group and one uninfected control) were analyzed in a dual-RNASeq fashion. We compared gene expression between three varying doses in the host and pathogen by contrasting experiment groups against the naïve control. Results A total of 4954 differentially expressed genes (DEGs) were detected after ASFV Ken12/1 infection, including 3055, 1771, and 128 DEGs in the high, medium, and low doses, respectively. Gene ontology and KEGG pathway analysis showed that the DEGs were enriched for genes involved in the innate immune response, inflammatory response, autophagy, and apoptosis in lethal dose groups. The surviving low dose group suppressed genes in pathways of physiopathological importance. We found a strong association between severe ASF pathogenesis in the high and medium dose groups with upregulation of proinflammatory cytokines and immunomodulation of cytokine expression possibly induced by overproduction of prostaglandin E synthase (4-fold; p < 0.05) or through downregulation of expression of M1-activating receptors, signal transductors, and transcription factors. The host-pathogen interaction resulted in induction of expression of immune-suppressive cytokines (IL-27), inactivation of autophagy and apoptosis through up-regulation of NUPR1 [5.7-fold (high dose) and 5.1-fold (medium dose) [p < 0.05] and IL7R expression. We detected repression of genes involved in MHC class II antigen processing and presentation, such as cathepsins, SLA-DQB1, SLA-DOB, SLA-DMB, SLA-DRA, and SLA-DQA in the medium and high dose groups. Additionally, the host-pathogen interaction activated the CD8+ cytotoxicity and neutrophil machinery by increasing the expression of neutrophils/CD8+ T effector cell-recruiting chemokines (CCL2, CXCL2, CXCL10, CCL23, CCL4, CXCL8, and CXCL13) in the lethal high and medium dose groups. The recovered pigs infected with ASFV at a low dose significantly repressed the expression of CXCL10, averting induction of T lymphocyte apoptosis and FUNDC1 that suppressed neutrophilia. Conclusions We provide the first in vivo gene expression profile data from locally-adapted pigs from south-western Kenya following experimental infection with a highly virulent ASFV genotype IX isolate at varying doses that mimic acute and mild disease. Our study showed that the locally-adapted pigs induced the expression of genes associated with tolerance to infection and repression of genes involved in inflammation at varying levels depending upon the ASFV dose administered.

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“…ASFV has evolved the ability to manipulate host immune responses by encoding many immune escape genes, including regulation of IFN expression, inhibition of autophagy, and apoptosis. In addition, ASFV affects the antigen presentation and activation of lymphocytes by invading monocytes-macrophages and DCs, thereby affecting the immune system of the entire body [ 31 ]. This review summarizes the escape mechanism of ASFV from the immune response and the progress of ASF vaccines, hoping to provide help for future ASF vaccines research.…”

Section: Introductionmentioning

confidence: 99%

Immune Escape Mechanism and Vaccine Research Progress of African Swine Fever Virus

Wang

Huang

et al. 2022

Vaccines

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African swine fever virus (ASFV) is the causative agent of the epidemic of African swine fever (ASF), with virulent strains having a mortality rate of up to 100% and presenting devastating impacts on animal farming. Since ASF was first reported in China in 2018, ASFV still exists and poses a potential threat to the current pig industry. Low-virulence and genotype I strains of ASFV have been reported in China, and the prevention and control of ASF is more complicated. Insufficient understanding of the interaction of ASFV with the host immune system hinders vaccine development. Physical barriers, nonspecific immune response and acquired immunity are the three barriers of the host against infection. To escape the innate immune response, ASFV invades monocytes/macrophages and dendritic cells, thereby inhibiting IFN expression, regulating cytokine expression and the body’s inflammatory response process. Meanwhile, in order to evade the adaptive immune response, ASFV inhibits antigen presentation, induces the production of non-neutralizing antibodies, and inhibits apoptosis. Recently, significant advances have been achieved in vaccine development around the world. Live attenuated vaccines (LAVs) based on artificially deleting specific virulence genes can achieve 100% homologous protection and partial heterologous protection. The key of subunit vaccines is identifying the combination of antigens that can effectively provide protection and selecting carriers that can effectively deliver the antigens. In this review, we introduce the epidemic trend of ASF and the impact on the pig industry, analyze the interaction mechanism between ASFV and the body’s immune system, and compare the current status of potential vaccines in order to provide a reference for the development of effective ASF vaccines.

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

Cited by 90 publications

References 90 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

Transcriptome profile of spleen tissues from locally-adapted Kenyan pigs (Sus scrofa) experimentally infected with three varying doses of a highly virulent African swine fever virus genotype IX isolate: Ken12/busia.1 (ken-1033)

Immune Escape Mechanism and Vaccine Research Progress of African Swine Fever Virus

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