Zhu Mingjun, Ma Xiaoqian, Cui Xiyao, Zhou Jing, Li Chengui, Huang Libo, Shang Yingli, Cheng Ziqiang
College of Veterinary Medicine, Shandong Agricultural University, Tai'an, 271018, China.
Oncotarget. 2017 Jul 19;8(35):58865-58871. doi: 10.18632/oncotarget.19378. eCollection 2017 Aug 29.
CCCH type zinc finger antiviral protein (ZAP) is a host restriction factor that inhibits the replication of a variety of viruses in mammals. However, little is known about its antiviral activity on avian tumor virus. Avian leukosis virus subgroup J (ALV-J), an oncogenic retrovirus, induces myelocytomas and various other tumors in meat and egg type chickens. Here, we identified a chicken ZAP (chZAP) that increased at early stage, and subsequently decreased after infection of ALV-J in DF-1 cells, indicating the inducible feature of the endogenous chZAP. To demonstrate the inhibitory effect on ALV-J replication by chZAP, we expressed exogenous chZAP by lentivirus based vectors in DF-1 cells that infected by ALV-J. The result showed that overexpression of chZAP significantly inhibited ALV-J replication at both mRNA level and protein level. Consequently, knockdown of endogenous chZAP by RNAi facilitated ALV-J replication in DF-1 cells. Further, we demonstrated that chZAP interacts with SU protein (encode by gp85 gene) of ALV-J in cytoplasm. Taken together, our results demonstrated that chZAP inhibits ALV-J by both mRNA and protein pathway and it may shed light on a novel antiviral approach in poultry.
CCCH型锌指抗病毒蛋白(ZAP)是一种宿主限制因子,可抑制多种病毒在哺乳动物中的复制。然而,关于其对禽肿瘤病毒的抗病毒活性知之甚少。禽白血病病毒J亚群(ALV-J)是一种致癌逆转录病毒,可在肉用和蛋用型鸡中诱发骨髓细胞瘤和各种其他肿瘤。在此,我们鉴定出一种鸡ZAP(chZAP),其在DF-1细胞中感染ALV-J后早期升高,随后降低,表明内源性chZAP具有诱导特性。为了证明chZAP对ALV-J复制的抑制作用,我们通过基于慢病毒的载体在感染ALV-J的DF-1细胞中表达外源性chZAP。结果表明,chZAP的过表达在mRNA水平和蛋白质水平均显著抑制ALV-J复制。因此,通过RNAi敲低内源性chZAP促进了ALV-J在DF-1细胞中的复制。此外,我们证明chZAP在细胞质中与ALV-J的SU蛋白(由gp85基因编码)相互作用。综上所述,我们的结果表明chZAP通过mRNA和蛋白质途径抑制ALV-J,这可能为家禽中的新型抗病毒方法提供线索。