title: ORF5 of porcine reproductive and respiratory syndrome virus (PRRSV) is a target of diversifying selection as infection progresses from acute infection to virus rebound.
abstract: Genetic variation in both structural and nonstructural genes is a key factor in the capacity of porcine reproductive and respiratory syndrome virus (PRRSV) to evade host defenses and maintain within animals, farms and metapopulations. However, the exact mechanisms by which genetic variation contribute to immune evasion remain unclear. In a study to understand the role of host genetics in disease resistance, a population of pigs were experimentally infected with a type 2 PRRSV isolate. Four pigs that showed virus rebound at 42days post-infection (dpi) were analyzed by 454 sequencing to characterize the rebound quasispecies. Deep sequencing of variable regions in nsp1, nsp2, ORF3 and ORF5 showed the largest number of nucleotide substitutions at day 28 compared to days 4 and 42 post-infection. Differences were also found in genetic variations when comparing tonsil versus serum. The results of dN/dS ratios showed that the same regions evolved under negative selection. However, eight amino acid sites were identified as possessing significant levels of positive selection, including A27V and N32S substitutions in the GP5 ectodomain region. These changes may alter GP5 peptide signal sequence processing and N-glycosylation, respectively. The results indicate that the greatest genetic diversity occurs during the transition between acute and rebound stages of infection, and the introduction of mutations that may result in a gain of fitness provides a potential mechanism for persistence.
authors.affiliation: Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, United States; College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, PR China. Electronic address: chnhlh@126.com.
authors.forename: Nanhua
authors.initials: N
authors.lastname: Chen
authors.affiliation: Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, United States.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Trible
authors.affiliation: Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, United States.
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Kerrigan
authors.affiliation: OIE Porcine Reproductive and Respiratory Syndrome Reference Laboratory, Beijing, PR China.
authors.forename: Kegong
authors.initials: K
authors.lastname: Tian
authors.affiliation: Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, United States.
authors.forename: Raymond R R
authors.initials: RRR
authors.lastname: Rowland
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D018450:Disease Progression; D014644:Genetic Variation; D016679:Genome, Viral; D009500:Neutralization Tests; D019318:Porcine Reproductive and Respiratory Syndrome / Q000821:virology*; D019316:Porcine respiratory and reproductive syndrome virus / Q000235:genetics* / Q000276:immunology; D012367:RNA, Viral; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D013552:Swine; D013997:Time Factors; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics*; D019562:Viral Load; D014766:Viremia
chemical_list: D012367:RNA, Viral; D014759:Viral Envelope Proteins; C114789:glycoprotein 5, PRRSV
keywords: Deep sequencing; Diversifying selection; Porcine reproductive and respiratory syndrome virus (PRRSV); Viral quasispecies; Virus rebound