African Swine Fever (ASF) is an acute, hot, high-contact animal infectious disease of domestic pigs and wild boars caused by the African Swine Fever virus (ASFV), which can be infected by pigs of all breeds and ages, with morbidity and mortality rates of up to 100%. As an animal disease that seriously endangers the healthy development of the global pig industry, there is an urgent need for safe and effective commercial vaccines.
Among them, the live attenuated vaccine for African swine fever is considered to be the most promising vaccine in the short term. Previous studies have shown that after the Georgian strain of African swine fever virus (ASFV-G-ΔA137R) missing the A137R gene infects pigs, the pathogenicity in vivo is reduced and it can provide complete protection against the attack of homologous strong strains, indicating that A137R is a virulence-related gene of ASFV, and ASFV-G-ΔA137R is also a potential ASF vaccine candidate.
However, the molecular mechanism by which the A137R protein regulates the pathogenicity of ASFV is unknown. Recently, the Innovation Team of the State Key Laboratory of Veterinary Biotechnology of the Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences (hereinafter referred to as "Harbin Veterinary Research Institute") published a new study in the Journal of Virology, and they have made new progress in analyzing the molecular mechanism of the natural immune response of the African swine fever virus escaping the host.
In this study, a recombinant ASFV (ASFV-ΔA137R) with the protein type II ASFV HLJ/18 strain (ASFV-WT) as the skeleton was constructed. Through transcriptome sequencing analysis, the research team found that primary pig alveolar macrophages infected with ASFV-ΔA137R induced higher levels of interferon I production compared to ASFV-WT. Mechanistic studies have shown that the A137R protein interacts with TBK1 and mediates tbK1 degradation through the autophagy-lysosomal pathway, thereby inhibiting the nuclear translocation of IRF3 and ultimately reducing the expression of type I interferons.
The research team believes that the study confirms that the A137R protein has the function of escaping the host's natural immune response, laying a foundation for resolving the molecular mechanism of the A137R protein to regulate the virulence of ASFV.
It is worth mentioning that since African swine fever, Harbin Veterinary Research Institute has been tackling vaccine research and development. In October 2019, the team of Bu Zhigao, director of the Harbin Veterinary Research Institute, and the team of academicians Rao Zihe and Wang Xiangxi of the Chinese Academy of Sciences published research in the international top academic journal Science, and they obtained the first high-definition map of the structure of the African swine fever virus, providing important clues for vaccine research and development.
Subsequently, in March 2020, the team of the State Key Laboratory of Veterinary Biotechnology and the National High-level Biosafety Laboratory for Animal Disease Prevention and Control published a study at SCIENCE CHINA Life Sciences (Science in China: Life Sciences).