Innate immune escape and adaptive immune evasion of African swine fever virus: A review

Niu, Sai; Guo, Yilin; Wang, Xueying; Wang, Zixuan; Sun, Limeng; Dai, Hanchuan; Peng, Guiqing

doi:10.1016/j.virol.2023.109878

Cited by 10 publications

(4 citation statements)

References 96 publications

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“…Despite previous reports on NF- κ B inhibitors encoded by ASFV, a comprehensive investigation into their mechanisms of action in vitro and in vivo , specifically regarding viral infection and pathogenicity, has not been detailed [ 42 , 43 ]. To investigate the molecular mechanism by which MGF300-4L inhibits the production of IL-1 β and TNF- α , we performed a protein–protein interaction analysis, which revealed the interactions between MGF300-4L and IKK β , as well as the interactions between MGF300-4L and I κ B α ( Figure 3 ).…”

Section: Discussionmentioning

confidence: 99%

The African swine fever virus MGF300-4L protein is associated with viral pathogenicity by promoting the autophagic degradation of IKK β and increasing the stability of I κ B α

Wang,

Luo,

Zhang

et al. 2024

Emerging Microbes & Infections

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African swine fever (ASF) is a highly contagious, often fatal viral disease caused by African swine fever virus (ASFV), which imposes a substantial economic burden on the global pig industry. When screening for the virus replication-regulating genes in the left variable region of the ASFV genome, we observed a notable reduction in ASFV replication following the deletion of the MGF300-4L gene. However, the role of MGF300-4L in ASFV infection remains unexplored. In this study, we found that MGF300-4L could effectively inhibit the production of proinflammatory cytokines IL-1 β and TNF- α , which are regulated by the NF- κ B signaling pathway. Mechanistically, we demonstrated that MGF300-4L interacts with IKK β and promotes its lysosomal degradation via the chaperone-mediated autophagy. Meanwhile, the interaction between MGF300-4L and I κ B α competitively inhibits the binding of the E3 ligase β -TrCP to I κ B α , thereby inhibiting the ubiquitination-dependent degradation of I κ B α . Remarkably, although ASFV encodes other inhibitors of NF- κ B, the MGF300-4L gene-deleted ASFV (Del4L) showed reduced virulence in pigs, indicating that MGF300-4L plays a critical role in ASFV pathogenicity. Importantly, the attenuation of Del4L was associated with a significant increase in the production of IL-1 β and TNF- α early in the infection of pigs. Our findings provide insights into the functions of MGF300-4L in ASFV pathogenicity, suggesting that MGF300-4L could be a promising target for developing novel strategies and live attenuated vaccines against ASF.

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Section: Discussionmentioning

confidence: 99%

The African swine fever virus MGF300-4L protein is associated with viral pathogenicity by promoting the autophagic degradation of IKK β and increasing the stability of I κ B α

Wang,

Luo,

Zhang

et al. 2024

Emerging Microbes & Infections

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“…ASFV has developed diverse strategies to manipulate host innate immunity, thereby facilitating viral replication ( Afe et al, 2023 ; Niu et al, 2023 ). Interferon-beta (IFN-β), a potent defense mechanism against viral infections, is typically antagonized or disarmed by the virus upon infection.…”

Section: Discussionmentioning

confidence: 99%

“…Modulation of host immunity is a prominent feature of ASFV, and this virus has evolved diverse strategies to counteract the host immunity, particularly concerning the cellular interferon signaling, a most critical line of host cellular defenses against invading organisms ( Afe et al, 2023 ; Niu et al, 2023 ). Recognition of viral pathogen-associated molecular pattern (PAMP), for example, the viral nucleic acids, by pattern recognition receptors (PRR) such as RIG-I/MDA-5, TLR, and cGAS leads to activation of transcription factors (e.g., IRF3, IRF7, NF-κB, etc.…”

Section: Introductionmentioning

confidence: 99%

African swine fever virus structural protein p17 inhibits IRF3 activation by recruiting host protein PR65A and inducing apoptotic degradation of STING

Wang,

Xiang,

Gao

et al. 2024

Front. Microbiol.

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African swine fever virus (ASFV) is notoriously known for evolving strategies to modulate IFN signaling. Despite lots of efforts, the underlying mechanisms have remained incompletely understood. This study concerns the regulatory role of viral inner membrane protein p17. We found that the ASFV p17 shows a preferential interaction with cGAS-STING-IRF3 pathway, but not the RIG-I-MAVS-NF-κB signaling, and can inhibit both poly(I:C)- and poly(A:T)-induced activation of IRF3, leading to attenuation of IFN-β induction. Mechanistically, p17 interacts with STING and IRF3 and recruits host scaffold protein PR65A, a subunit of cellular phosphatase PP2A, to down-regulate the level of p-IRF3. Also, p17 targets STING for partial degradation via induction of cellular apoptosis that consequently inhibits activation of both p-TBK1 and p-IRF3. Thus, our findings reveal novel regulatory mechanisms for p17 modulation of IFN signaling and shed light on the intricate interplay between ASFV proteins and host immunity.

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“…It benefits ASFV to inhibit inflammation and coagulation cascades to allow the host to survive, thereby producing and shedding more viruses. Previous studies identified a number of ASFV genes, such as I329L, DP96R, L83L, F317L, A238L, and so on, that could inhibit the identified inflammation [ 33 ]; however, no gene in ASFV has been reported to able to affect coagulation cascades directly.…”

Section: Introductionmentioning

confidence: 99%

African Swine Fever Virus I267L Is a Hemorrhage-Related Gene Based on Transcriptome Analysis

Wen,

Duan,

Ren

et al. 2024

Microorganisms

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African swine fever (ASF) is an acute and severe disease transmitted among domestic pigs and wild boars. This disease is notorious for its high mortality rate and has caused great losses to the world’s pig industry in the past few years. After infection, pigs can develop symptoms such as high fever, inflammation, and acute hemorrhage, finally leading to death. African swine fever virus (ASFV) is the causal agent of ASF; it is a large DNA virus with 150–200 genes. Elucidating the functions of each gene could provide insightful information for developing prevention and control methods. Herein, to investigate the function of I267L, porcine alveolar macrophages (PAMs) infected with an I267L-deleted ASFV strain (named ∆I267L) and wild-type ASFV for 18 h and 36 h were taken for transcriptome sequencing (RNA-seq). The most distinct different gene that appeared at both 18 hpi (hours post-infection) and 36 hpi was F3; it is the key link between inflammation and coagulation cascades. KEGG analysis (Kyoto encyclopedia of genes and genomes analysis) revealed the complement and coagulation cascades were also significantly affected at 18 hpi. Genes associated with the immune response were also highly enriched with the deletion of I267L. RNA-seq results were validated through RT-qPCR. Further experiments confirmed that ASFV infection could suppress the induction of F3 through TNF-α, while I267L deletion partially impaired this suppression. These results suggest that I267L is a pathogenicity-associated gene that modulates the hemorrhages of ASF by suppressing F3 expression. This study provides new insights into the molecular mechanisms of ASFV pathogenicity and potential targets for ASFV prevention and control.

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Innate immune escape and adaptive immune evasion of African swine fever virus: A review

Cited by 10 publications

References 96 publications

The African swine fever virus MGF300-4L protein is associated with viral pathogenicity by promoting the autophagic degradation of IKK β and increasing the stability of I κ B α

The African swine fever virus MGF300-4L protein is associated with viral pathogenicity by promoting the autophagic degradation of IKK β and increasing the stability of I κ B α

African swine fever virus structural protein p17 inhibits IRF3 activation by recruiting host protein PR65A and inducing apoptotic degradation of STING

African Swine Fever Virus I267L Is a Hemorrhage-Related Gene Based on Transcriptome Analysis

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