title: Nsp9 and Nsp10 contribute to the fatal virulence of highly pathogenic porcine reproductive and respiratory syndrome virus emerging in China.
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.
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis of the Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis of the Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis of the Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Jialong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis of the Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Xinna
authors.initials: X
authors.lastname: Ge
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis of the Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis of the Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Huaguo
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis of the Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Geng
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis of the Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis of the Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Hanchun
authors.initials: H
authors.lastname: Yang
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D019318:Porcine Reproductive and Respiratory Syndrome / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D019316:Porcine respiratory and reproductive syndrome virus / Q000472:pathogenicity / Q000502:physiology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D013552:Swine; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology*
chemical_list: D016601:RNA-Binding Proteins; D014764:Viral Proteins; D037521:Virulence Factors