African Swine Fever Virus pF778R Attenuates Type I Interferon Response by Impeding STAT1 Nuclear Translocation

Chen, Qichao; Li, Liang; Liu, Lixinjie; Liu, Zhankui; Guo, Shibang; Tan, Chen; Chen, Huanchun; Wang, Xiangru

doi:10.1016/j.virusres.2023.199190

Cited by 4 publications

(2 citation statements)

References 70 publications

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“…IL-10 levels remained stable in surviving pigs, while IL-10 levels increased significantly in dead pigs ( 24 , 32 , 42 , 45 – 47 ). ASFV has evolved several strategies to inhibit IFN-α secretion, such as the pH240R protein that inhibits IFN-α production by disrupting STING oligomerization ( 48 ), pF778R that attenuates the I type interferon response ( 49 ). In this study, the IFN-α in the serum did not change in the early stage of infection, but the level of IFN-α increased significantly after the fever in domestic pigs.…”

Section: Discussionmentioning

confidence: 99%

Infection of domestic pigs with a genotype II potent strain of ASFV causes cytokine storm and lymphocyte mass reduction

Zuo,

Peng,

Zhao

et al. 2024

Front. Immunol.

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The whole-genome sequence of an African swine fever virus (ASFV) strain (HuB/HH/2019) isolated from Hubei, China, was highly similar to that of the Georgia 2007/1 strain ASFV. After infection with strong strains, domestic pigs show typical symptoms of infection, including fever, depression, reddening of the skin, hemorrhagic swelling of various tissues, and dysfunction. The earliest detoxification occurred in pharyngeal swabs at 4 days post-infection. The viral load in the blood was extremely high, and ASFV was detected in multiple tissues, with the highest viral loads in the spleen and lungs. An imbalance between pro- and anti-inflammatory factors in the serum leads to an excessive inflammatory response in the body. Immune factor expression is suppressed without effectively eliciting an immune defense. Antibodies against p30 were not detected in acutely dead domestic pigs. Sequencing of the peripheral blood mononuclear cell transcriptome revealed elevated transcription of genes associated with immunity, defense, and stress. The massive reduction in lymphocyte counts in the blood collapses the body’s immune system. An excessive inflammatory response with a massive reduction in the lymphocyte count may be an important cause of mortality in domestic pigs. These two reasons have inspired researchers to reduce excessive inflammatory responses and stimulate effective immune responses for future vaccine development.

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Section: Discussionmentioning

confidence: 99%

Infection of domestic pigs with a genotype II potent strain of ASFV causes cytokine storm and lymphocyte mass reduction

Zuo,

Peng,

Zhao

et al. 2024

Front. Immunol.

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show abstract

“…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. Some of the viral factors that control this pathway during ASFV infection [21][22][23][24][25] have also been identified. The identification and study of these factors are fundamental for the development of live attenuated vaccines (LAVs), which are currently the most realistic strategy for developing a vaccine against ASFV.…”

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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Helicobacter pylori activates SLFN4+MDSCs to accelerate gastric intestinal metaplasia

Zhao,

Liu,

Peng

et al. 2024

iScience

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African Swine Fever Virus pF778R Attenuates Type I Interferon Response by Impeding STAT1 Nuclear Translocation

Cited by 4 publications

References 70 publications

Infection of domestic pigs with a genotype II potent strain of ASFV causes cytokine storm and lymphocyte mass reduction

Infection of domestic pigs with a genotype II potent strain of ASFV causes cytokine storm and lymphocyte mass reduction

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

Helicobacter pylori activates SLFN4+MDSCs to accelerate gastric intestinal metaplasia

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