# African swine fever virus pB318L suppresses inflammatory response by inhibiting NF-κB activation and NLRP3 inflammasome formation

## TL;DR

This study reveals how the African swine fever virus protein pB318L suppresses the host's immune response, offering new insights for developing antiviral strategies.

## Contribution

The study identifies pB318L as a key ASFV protein that inhibits NF-κB and NLRP3 inflammasome activation independently of its enzymatic activity.

## Key findings

- pB318L inhibits NF-κB signaling by interacting with NEMO and blocking TRIM21-mediated ubiquitination.
- pB318L prevents NLRP3 inflammasome formation by interacting with NACHT and LRR domains of NLRP3.
- The immunosuppressive effects of pB318L are independent of its GGPPS enzymatic activity.

## Abstract

African swine fever (ASF) is an acute, hemorrhagic, and severe infectious disease caused by African swine fever virus (ASFV), posing significant threats to global swine production. ASFV pathogenesis is closely associated with its sophisticated immune evasion strategies. In this study, we demonstrate that ASFV pB318L, a trans-geranylgeranyl-diphosphate synthase (GGPPS) homolog inhibited both the NF-κB signaling pathway and the formation of the NLRP3 inflammasome. Infection with ASFV-intB318L (a recombinant ASFV with pB318L expression inhibition) induced significantly higher levels of IL-1β compared to its parent strain ASFV HLJ/18. Mechanically, pB318L interacts with NEMO to inhibit the interaction between IKKα and NEMO, and suppresses the K63-linked ubiquitination of NEMO mediated by TRIM21. In addition, pB318L interacts with the NACHT and LRR domains of NLRP3, which prevents the oligomerization of NLRP3 by suppressing the interaction between NEK7 and NLRP3. Crucially, the immunosuppressive functions of pB318L on both NF-κB signaling pathway and NLRP3 inflammasome activation are independent of its GGPPS enzymatic activity. In conclusion, we presented evidence that ASFV pB318L negatively regulates NF-κB signaling pathway and NLRP3 inflammasome. This study provides critical mechanistic insights into the role of pB318L in ASFV pathogenesis and highlights its potential as a target for the development of antiviral strategies or live-attenuated vaccines against ASF.

ASF is an acute hemorrhagic infectious disease caused by ASFV, which has a serious impact on the global pig industry. The importance of this article lies in revealing the crucial role of ASFV pB318L in viral infection, particularly in how it evades the host’s innate immune response by inhibiting the activation of the NF-κB signaling pathway and NLRP3 inflammasome. This discovery not only deepens our understanding of the biological characteristics of ASFV, but also provides new research clues for the development of antiviral drugs or live vaccines against ASF. By investigating the interaction between pB318L and NEMO, as well as pB318L and NLRP3, this article provides a critical mechanistic explanation of how ASFV promotes its own survival by modulating host immune mechanisms. In addition, these findings lay the foundation for the prevention and control strategies of ASF in the future, especially in the context of the increasingly urgent global need to manage ASF outbreaks. Therefore, the research results of this study hold important theoretical and practical implication for fields such as public health, animal disease prevention and control, and agricultural economics.