Inhibition of avian tumor virus replication by CCCH-type zinc finger antiviral protein.

Mingjun Zhu,Yingli Shang,Jing Zhou,Xiyao Cui,Ziqiang Cheng,Chengui Li,Xiaoqian Ma,Libo Huang

doi:10.18632/oncotarget.19378

Mingjun Zhu, Yingli Shang + Show 6 more

Open Access

https://doi.org/10.18632/oncotarget.19378

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Journal: Oncotarget	Publication Date: Jul 19, 2017
Citations: 18	License type: cc-by

Affiliation: Shandong Agricultural University

Abstract

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.

Highlights

Host restriction factors play critical roles in control of retrovirus replication [1]
Endogenous chicken ZAP (chZAP) expression was induced by infection of Avian leukosis virus subgroup J (ALV-J)
To understand whether endogenous chZAP expression was affected by ALV-J infection in cells, we examined the endogenous chZAP changes by Quantitative real time RT-PCR (qPCR), western blot before and after infection of ALV-J in DF-1 cells

Summary

Introduction

Host restriction factors play critical roles in control of retrovirus replication [1]. A number of powerful host restriction factors that inhibit retrovirus replication have been identified in mammals including APOBEC3, TRIM5, KAP1/TRIM28/ZFP809, SAMHD1, Tetherin and the CCCH type zinc finger antiviral protein (ZAP) [2,3,4,5,6,7]. ZAP was initially identified in rat as a host restriction factor that prevents cells from infection with the moloney murine leukemia virus (MMLV) [3]. ZAP is a host restriction factor of the innate immune system, ZAP does not induce a universal antiviral state because some viruses, such as herpes simplex virus type 1 and yellow fever virus, can replicate normally in ZAP-overexpressing cells [9]. ZAP recognizes the target virus transcripts via its CCCH type zinc-finger domains and binds to RNA helicases and components of the exosome to induce the degradation of virus transcripts [13,14,15,16,17]

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