Sheng Chun, Liu Xiaoxiang, Jiang Qiuyue, Xu Bin, Zhou Chenhao, Wang Yujing, Chen Jun, Xiao Ming
College of Life and Environment Sciences, Shanghai Normal University, Shanghai, PR China.
J Gen Virol. 2015 May;96(Pt 5):1027-1032. doi: 10.1099/vir.0.000048. Epub 2015 Jan 15.
Annexin A2 (ANXA2) is an important host factor regulating several key processes in many viruses. To evaluate the potential involvement of ANXA2 in the life cycle of classical swine fever virus (CSFV), an RNA interference (RNAi) approach was utilized. Knockdown of ANXA2 did not impair CSFV RNA replication but significantly reduced CSFV production. A comparable reduction of extracellular and intracellular infectivity levels was detected, indicating that ANXA2 might play a role in CSFV assembly rather than in genome replication and virion release. Furthermore, ANXA2 was found to bind CSFV NS5A, an essential replicase component. Amino acids R338, N359, G378 of NS5A were revealed to be pivotal for the ANXA2-NS5A interaction. Substitutions of these amino acids had no effect on viral RNA replication but substantially reduced CSFV production, which might partly be due to these mutations destroying the ANXA2-NS5A interaction. These results suggested that ANXA2 might participate in CSFV production process by binding NS5A.
膜联蛋白A2(ANXA2)是一种重要的宿主因子,可调节多种病毒的几个关键过程。为了评估ANXA2在经典猪瘟病毒(CSFV)生命周期中的潜在作用,采用了RNA干扰(RNAi)方法。敲低ANXA2并不损害CSFV RNA复制,但显著降低了CSFV的产生。检测到细胞外和细胞内感染性水平有类似程度的降低,表明ANXA2可能在CSFV组装中起作用,而不是在基因组复制和病毒粒子释放中起作用。此外,发现ANXA2与CSFV NS5A(一种必需的复制酶成分)结合。NS5A的氨基酸R338、N359、G378被揭示对ANXA2-NS5A相互作用至关重要。这些氨基酸的替换对病毒RNA复制没有影响,但显著降低了CSFV的产生,这可能部分是由于这些突变破坏了ANXA2-NS5A相互作用。这些结果表明,ANXA2可能通过与NS5A结合参与CSFV的产生过程。