title: Genomic sequencing reveals mutations potentially related to the overattenuation of a highly pathogenic porcine reproductive and respiratory syndrome virus.
abstract: Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) continues to evolve when serially passaged in Marc-145 cells. In this study, we analyzed the genomic and antigenic variants of HP-PRRSV strain JXA1 during in vitro passage. Protective efficacies of JXA1 from passages 100, 110, 120, 140, and 170 against the high-virulence parental virus were evaluated by inoculating pigs with each of these viruses and then challenging with JXA1 from passage 5 at 28 days postimmunization. We found that the antigenicities of JXA1 from passages after 110 were significantly reduced. Inoculation with JXA1 from passages after 110 provided only insufficient protection against the parental strain challenge, indicating that the immunogenicity of JXA1 is significantly decreased when it is in vitro passaged for 110 times and more. To identify the genomic variants that emerged during the overattenuation, eight complete genomes of highly passaged JXA1 were sequenced. One guanine deletion in the 5' untranslated region (UTR), two nucleotide substitutions in the 3' UTR, and 65 amino acid mutations in nonstructural and structural proteins that accompanied with the attenuation and overattenuation were determined. Genomic sequencing of in vitro serially passaged HP-PRRSV first identified the mutations potentially correlated with the overattenuation of a HP-PRRSV strain. These results facilitate the research aimed at elucidating the mechanisms for PRRSV genomic and antigenic changes and may also contribute to developing a safe and effective PRRSV vaccine.
authors: Veterinary Diagnostic Lab, China Animal Disease Control Center, Beijing, People's Republic of China.
authors: Xiuling
authors: X
authors: Yu
authors: Nanhua
authors: N
authors: Chen
authors: Xiaoyu
authors: X
authors: Deng
authors: Zhen
authors: Z
authors: Cao
authors: Wei
authors: W
authors: Han
authors: Dongmei
authors: D
authors: Hu
authors: Jiajun
authors: J
authors: Wu
authors: Shuo
authors: S
authors: Zhang
authors: Baoyue
authors: B
authors: Wang
authors: Xiaoxue
authors: X
authors: Gu
authors: Kegong
authors: K
authors: Tian
mesh_terms: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D016679:Genome, Viral; D009154:Mutation; D017354:Point Mutation; D019318:Porcine Reproductive and Respiratory Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D019316:Porcine respiratory and reproductive syndrome virus / Q000235:genetics* / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D012367:RNA, Viral / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012692:Serial Passage; D016019:Survival Analysis; D013552:Swine; D017361:Viral Nonstructural Proteins / Q000235:genetics; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014774:Virulence
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; D014765:Viral Vaccines