Combinational Deletions of <i>MGF110-9L</i> and <i>MGF505-7R</i> Genes from the African Swine Fever Virus Inhibit TBK1 Degradation by an Autophagy Activator PIK3C2B To Promote Type I Interferon Production
Guoqiang Zhu, Jingjing Ren, Dan Li, Yi Ru, Xiaodong Qin, Tao Feng, Hong Tian, Bingzhou Lu, Dongfang Shi, Zhengwang Shi, Wenping Yang, Haixue Zheng
Abstract
African swine fever (ASF) is a contagious and lethal hemorrhagic disease of pigs caused by the African swine fever virus (ASFV), leading to significant economic consequences for the global pig industry. The development of an effective and safe ASF vaccine has been unsuccessful. Previous studies have shown that live attenuated vaccines (LAVs) of ASFV are the most effective vaccine candidates to prevent ASF. Understanding the host responses caused by LAVs of ASFV is important in optimizing vaccine design and diversifying the resources available to control ASF. Recently, our laboratory found that the live attenuated ASFV-Δ110-9L/505-7R provided complete protection against parental ASFV-WT challenge. This study further demonstrated that ASFV-Δ110-9L/505-7R inhibits TBK1 degradation mediated by an autophagy activator PIK3C2B to increase type I interferon production. These results revealed an important mechanism for candidate vaccine ASFV-Δ110-9L/505-7R, providing strategies for exploring the virulence of multigene-deleted live attenuated ASFV strains and the development of vaccines.