FMDV 3A Antagonizes the Effect of ANXA1 to Positively Modulate Viral Replication
Xusheng Ma, Keshan Zhang, Zhikuan Luo, Xiaofeng Nian, Sk Mohiuddin Choudhury, Zixiang Zhu, Rui Song, Jingjing Pei, Yanli Huo, Yuanyuan Li, Fan Yang, Weijun Cao, Huisheng Liu, Xiangtao Liu, Haixue Zheng
Abstract
FMDV is a pathogen that causes one of the world's most destructive and highly contagious animal diseases. The FMDV 3A protein plays a critical role in viral replication and host range. Although 3A is one of the viral proteins that influences FMDV virulence, its underlying mechanisms remain unclear. ANXA1 is involved in immune activation against pathogens. The present study demonstrated that FMDV increases ANXA1 expression, while ANXA1 inhibits FMDV replication. The results also showed that ANXA1 promotes RNA virus-induced IFN-I production through the IRF3 axis at VISA and TBK1 levels. ANXA1 was also found to interact with JAK1 and STAT1 to strengthen signal transduction induced by IFN-β and IFN-γ. 3A interacted with ANXA1 to inhibit ANXA1-TBK1 complex formation, thereby antagonizing the inhibitory effect of ANXA1 on FMDV replication. This study helps to elucidate the mechanism underlying the effect of the 3A protein on FMDV replication.