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J Virol. 2019 May 1;93(10). pii: e00001-19. doi: 10.1128/JVI.00001-19. Print 2019 May 15.

ZAP, a CCCH-Type Zinc Finger Protein, Inhibits Porcine Reproductive and Respiratory Syndrome Virus Replication and Interacts with Viral Nsp9.

Author information

1
Key Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of Agriculture MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
2
Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
3
Key Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of Agriculture MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China jiangp@njau.edu.cn.
4
Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important pathogens affecting many swine-producing regions. Current vaccination strategies and antiviral drugs provide only limited protection. PRRSV infection can cleave mitochondrial antiviral signaling protein (MAVS) and inhibit the induction of type I interferon. The antiviral effector molecules that are involved in host protective responses to PRRSV infection are not fully understood. Here, by using transcriptome sequencing, we found that a zinc finger antiviral protein, ZAP, is upregulated in MAVS-transfected Marc-145 cells and that ZAP suppresses PRRSV infection at the early stage of replication. We also found that the viral protein Nsp9, an RNA-dependent RNA polymerase (RdRp), interacts with ZAP. The interacting locations were mapped to the zinc finger domain of ZAP and N-terminal amino acids 150 to 160 of Nsp9. These findings suggest that ZAP is an effective antiviral factor for suppressing PRRSV infection, and they shed light on virus-host interaction.IMPORTANCE PRRSV continues to adversely impact the global swine industry. It is important to understand the various antiviral factors against PRRSV infection. Here, a zinc finger protein, termed ZAP, was screened from MAVS-induced antiviral genes by transcriptome sequencing, and it was found to remarkably suppress PRRSV replication and interact with PRRSV Nsp9. The zinc finger domain of ZAP and amino acids 150 to 160 of Nsp9 are responsible for the interaction. These findings expand the antiviral spectrum of ZAP and provide a better understanding of ZAP antiviral mechanisms, as well as virus-host interactions.

KEYWORDS:

Antiviral factor; Nsp9; PRRSV replication; ZAP; interaction

PMID:
30867303
PMCID:
PMC6498049
[Available on 2019-11-01]
DOI:
10.1128/JVI.00001-19

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