title: Significance of genetic variation of PRRSV ORF5 in virus neutralization and molecular determinants corresponding to cross neutralization among PRRS viruses.
abstract: A high rate of genetic and antigenic variability among porcine reproductive and respiratory syndrome viruses (PRRSVs) hampers effective prevention and control of the disease caused by PRRSV. The major envelope protein (GP5) encoded by the ORF5 of PRRSV has a critical role in inducing virus neutralizing (VN) antibody and cross protection among different strains of PRRSV. This study was conducted to identify sequence elements related to cross neutralization by comparing the ORF5 sequences of 69 field isolates in conjunction with their susceptibility to VN antibody raised against the VR2332 strain in vitro and in vivo. Five common variable sites (amino acid position 32-34, 38-39, 57-59, 137 and 151) were identified between susceptible and resistant viral isolates. Mutants whose ORF5 amino acid sequences were substituted with the sequences corresponding to the 5 identified common variable sites individually or concurrently were generated from a VR2332-backboned infectious clone by site mutagenesis. The change in the susceptibility of the mutants to VN antibodies specific for VR2332 or a heterologous PRRSV was assessed to determine the association of those 5 identified sites with cross neutralization. Among the five sites, the changes of amino acid sequences at three sites (32-34, 38-39, and 57-59) located in the N-terminal ectodomain of ORF5 significantly influenced the susceptibility of the mutant viruses to VN antibody, suggesting that sequence homology at these sites can be utilized as genetic markers to predict the degree of cross neutralization among different PRRSVs.
authors.affiliation: Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.
authors.forename: Won-Il
authors.initials: WI
authors.lastname: Kim
authors.forename: Jae-Jo
authors.initials: JJ
authors.lastname: Kim
authors.forename: Sang-Ho
authors.initials: SH
authors.lastname: Cha
authors.forename: Wai-Hong
authors.initials: WH
authors.lastname: Wu
authors.forename: Vickie
authors.initials: V
authors.lastname: Cooper
authors.forename: Rich
authors.initials: R
authors.lastname: Evans
authors.forename: En-Jin
authors.initials: EJ
authors.lastname: Choi
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Yoon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003429:Cross Reactions; D014644:Genetic Variation; D005838:Genotype; D007116:Immunization, Passive; D007136:Immunoglobulins / Q000276:immunology / Q000494:pharmacology; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009500:Neutralization Tests; D019318:Porcine Reproductive and Respiratory Syndrome / Q000517:prevention & control / Q000821:virology; D019316:Porcine respiratory and reproductive syndrome virus / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification; D016415:Sequence Alignment; D013552:Swine; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000276:immunology
chemical_list: D007136:Immunoglobulins; D014759:Viral Envelope Proteins; C114789:glycoprotein 5, PRRSV