Nsp9 and Nsp10 contribute to the fatal virulence of highly pathogenic porcine reproductive and respiratory syndrome virus emerging in China.

Yan Li,Huaguo Zheng,Jialong Zhang,Rong Zhou,Xin Guo,Lei Zhou,Gang Geng,Xinna Ge,Hanchun Yang,Michael P Murtaugh

doi:10.1371/journal.ppat.1004216

Abstract

Atypical porcine reproductive and respiratory syndrome (PRRS), which is caused by the Chinese highly pathogenic PRRS virus (HP-PRRSV), has resulted in large economic loss to the swine industry since its outbreak in 2006. However, to date, the region(s) within the viral genome that are related to the fatal virulence of HP-PRRSV remain unknown. In the present study, we generated a series of full-length infectious cDNA clones with swapped coding regions between the highly pathogenic RvJXwn and low pathogenic RvHB-1/3.9. Next, the in vitro and in vivo replication and pathogenicity for piglets of the rescued chimeric viruses were systematically analyzed and compared with their backbone viruses. First, we swapped the regions including the 5′UTR+ORF1a, ORF1b, and structural proteins (SPs)-coding region between the two viruses and demonstrated that the nonstructural protein-coding region, ORF1b, is directly related to the fatal virulence and increased replication efficiency of HP-PRRSV both in vitro and in vivo. Furthermore, we substituted the nonstructural protein (Nsp) 9-, Nsp10-, Nsp11- and Nsp12-coding regions separately; or Nsp9- and Nsp10-coding regions together; or Nsp9-, Nsp10- and Nsp11-coding regions simultaneously between the two viruses. Our results indicated that the HP-PRRSV Nsp9- and Nsp10-coding regions together are closely related to the replication efficiency in vitro and in vivo and are related to the increased pathogenicity and fatal virulence for piglets. Our findings suggest that Nsp9 and Nsp10 together contribute to the fatal virulence of HP-PRRSV emerging in China, helping to elucidate the pathogenesis of this virus.

Highlights

Porcine reproductive and respiratory syndrome (PRRS) is characterized by reproductive failure in sows and respiratory diseases in all ages of pigs [1,2]
Our findings suggest that Nsp9 and Nsp10 together contribute to the fatal virulence of HP-PRRSV emerging in China, helping to elucidate the pathogenesis of this virus
HP-PRRSV still circulates in the field as the dominant virus, which may increase the diversity of PRRSV due to the possibility of viral recombination [63,64]

Summary

Introduction

Porcine reproductive and respiratory syndrome (PRRS) is characterized by reproductive failure in sows and respiratory diseases in all ages of pigs [1,2]. This disease was first reported in the United States in the late 1980s [3], and in Germany in 1990, and this disease became widespread throughout the world [4,5]. Based on genetic and antigenic characteristics, two major genotypes of PRRSV, type 1 (European) and type 2 (North American), have been identified and share approximately 55–70% nucleotide identity [14]. The phylogenic analyses of the ORF7 sequence show that the European PRRSV can further be divided into three subtypes, pan European subtype 1 and East European subtypes 2 and 3 [15], and the North American PRRSV can be classified into at least 9 distinct genetic lineages [16]

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