Antiviral immunotoxin against Bovine herpesvirus-1:targeted inhibition of viral replication and apop

• 作 者: Jian Xu Xiaoyang Li Bo Jiang Xiaoyu Feng Jing Wu Yunhong Cai Xixi Zhang Xiufen Huang Joshua E.Sealy Munir Iqbal Yongqing Li
• 机 构: Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry,Be
• 出 处: 第六届京津冀一体化畜牧兽医科技创新研讨会暨新思想、新方法、新观点论坛
• 发表日期: 2018年9期
• 关键词: Bovine herpesvirus-1 immunotoxin antiviral function specific binding targeted cy

　　Bovine herpesvirus 1(BoHV-1)is a highly contagious viral pathogen which causes infectious bovine rhinotracheitis in cattle worldwide.Currently,there is no antiviral prophylactic treatment available capable of mitigating the disease impact and facilitating recovery from latent infection.In this study,we have engineered a novel recombinant anti-BoHV-1 immunotoxin construct termed “BoScFv-PE38” that consists of a single-chain monoclonal antibody fragment(scFv)fused with an active domain of Pseudomonas exotoxin A as a toxic effector(PE38).The recombinant BoScFv-PE38 immunotoxin expressed in a prokaryotic expression system has specific binding affinity for BoHV-1 glycoprotein D(gD)with a dissociation constant(Kd)of 12.81 nM and for BoHV-1 virus particles with a Kd value of 97.63 nM.We demonstrate that the recombinant BoScFv-PE38 is internalized into MDBK cell compartments that inhibit BoHV-1 replication with a half-maximal inhibitory concentration(IC50)of 4.95±0.33 nM and a selective index(SI)of 456±31.Furthermore,the BoScFv-PE38 exerted a cytotoxic effect through the induction of ATP and ammonia,leading to apoptosis of BoHV-1-infected cells and the inhibition of BoHV-1 replication in MDBK cells.Collectively,we show that BoScFv-PE38 can potentially be employed as a therapeutic agent for the treatment of BoHV-1 infection.