Helicase of Type 2 Porcine Reproductive and Respiratory Syndrome Virus Strain HV Reveals a Unique Structure.

Chenjun Tang,Zengqin Deng,Gongyi Zhang,Zhenhang Chen,Xiaorong Li,Zizi Tian,Zhongzhou Chen,Wen-Hai Feng,Meiting Yang,Wei Wu,Guoguo Wang

doi:10.3390/v12020215

Chenjun Tang, Zengqin Deng + Show 9 more

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https://doi.org/10.3390/v12020215

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Journal: Viruses	Publication Date: Feb 14, 2020
Citations: 19	License type: CC BY 4.0

Affiliation: China Agricultural University

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is prevalent throughout the world and has caused great economic losses to the swine industry. Nonstructural protein 10 (nsp10) is a superfamily 1 helicase participating in multiple processes of virus replication and one of the three most conserved proteins in nidoviruses. Here we report three high resolution crystal structures of highly pathogenic PRRSV nsp10. PRRSV nsp10 has multiple domains, including an N-terminal zinc-binding domain (ZBD), a β-barrel domain, a helicase core with two RecA-like domains, and a C-terminal domain (CTD). The CTD adopts a novel fold and is required for the overall structure and enzymatic activities. Although each domain except the CTD aligns well with its homologs, PRRSV nsp10 adopts an unexpected extended overall structure in crystals and solution. Moreover, structural and functional analyses of PRRSV nsp10 versus its closest homolog, equine arteritis virus nsp10, suggest that DNA binding might induce a profound conformational change of PRRSV nsp10 to exert functions, thus shedding light on the mechanisms of activity regulation of this helicase.

Highlights

Porcine reproductive and respiratory syndrome (PRRS) is characterized by reproductive failure in sows and respiratory diseases in piglets [1,2]
We previously reported the first structure of the nidovirus helicase, equine arteritis virus (EAV; family Arteriviridae) nsp10, and demonstrated that the C-terminal domain (CTD) perhaps exerts a regulatory function on the helicase core, facilitating coupling between NTPase and polynucleotide binding activities [23]
Basic Local Alignment Search Tool (BLAST) searches of the porcine reproductive and respiratory syndrome virus (PRRSV) nsp10 sequence among the solved structures in the Protein Data Bank (PDB) database revealed that the sequence identities with known structures were low, with the highest value being only 30%

Summary

Introduction

Porcine reproductive and respiratory syndrome (PRRS) is characterized by reproductive failure in sows and respiratory diseases in piglets [1,2]. This disease is one of the most infectious diseases in the swine industry worldwide and has brought great economic losses since it was first reported in the late 1980s [3,4]. The etiological agent, porcine reproductive and respiratory syndrome virus (PRRSV), is a single positive-stranded RNA virus, which is classified into two genotypes: the type 1. The PRRSV genome is approximately 15.4 kb in length and includes at least 12 open reading frames (ORFs). The ORF1a and ORF1b encode polyproteins pp1a and pp1ab, which are subsequently processed into many functional nonstructural proteins (nsps) essential for virus replication, genomic transcription, viral pathogenesis, and virulence [8,9,10,11,12]

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