PMID- 28509878 OWN - NLM STAT- MEDLINE DCOM- 20180123 LR - 20181113 IS - 1999-4915 (Electronic) IS - 1999-4915 (Linking) VI - 9 IP - 5 DP - 2017 May 16 TI - Antigenic and Biological Characterization of ORF2-6 Variants at Early Times Following PRRSV Infection. LID - 10.3390/v9050113 [doi] LID - 113 AB - Genetic diversity of porcine reproductive and respiratory syndrome virus (PRRSV) challenges efforts to develop effective and broadly acting vaccines. Although genetic variation in PRRSV has been extensively documented, the effects of this variation on virus phenotype are less well understood. In the present study, PRRSV open reading frame (ORF)2-6 variants predominant during the first six weeks following experimental infection were characterized for antigenic and replication phenotype. There was limited genetic variation during these early times after infection; however, distinct ORF2-6 haplotypes that differed from the NVSL97-7895 inoculum were identified in each of the five pigs examined. Chimeric viruses containing all or part of predominant ORF2-6 haplotypes were constructed and tested in virus neutralization and in vitro replication assays. In two pigs, genetic variation in ORF2-6 resulted in increased resistance to neutralization by autologous sera. Mapping studies indicated that variation in either ORF2-4 or ORF5-6 could confer increased neutralization resistance, but there was no single amino acid substitution that was predictive of neutralization phenotype. Detailed analyses of the early steps in PRRSV replication in the presence and absence of neutralizing antibody revealed both significant inhibition of virion attachment and, independently, a significant delay in the appearance of newly synthesized viral RNA. In all pigs, genetic variation in ORF2-6 also resulted in significant reduction in infectivity on MARC-145 cells, suggesting variation in ORF2-6 may also be important for virus replication in vivo. Together, these data reveal that variation appearing early after infection, though limited, alters important virus phenotypes and contributes to antigenic and biologic diversity of PRRSV. FAU - Evans, Alyssa B AU - Evans AB AD - Department of Animal Science, Iowa State University, Ames, IA 50011, USA. alyssa.ben.evans@gmail.com. FAU - Loyd, Hyelee AU - Loyd H AD - Department of Animal Science, Iowa State University, Ames, IA 50011, USA. heri1008@iastate.edu. FAU - Dunkelberger, Jenelle R AU - Dunkelberger JR AD - Department of Animal Science, Iowa State University, Ames, IA 50011, USA. jenelled@iastate.edu. FAU - van Tol, Sarah AU - van Tol S AD - Department of Animal Science, Iowa State University, Ames, IA 50011, USA. savantol@utmb.edu. FAU - Bolton, Marcus J AU - Bolton MJ AD - Department of Animal Science, Iowa State University, Ames, IA 50011, USA. mjohnbolton@gmail.com. FAU - Dorman, Karin S AU - Dorman KS AD - Departments of Statistics and Genetics, Development and Cell Biology, Iowa State University, Ames, IA 50011, USA. kdorman@iastate.edu. FAU - Dekkers, Jack C M AU - Dekkers JCM AD - Department of Animal Science, Iowa State University, Ames, IA 50011, USA. jdekkers@iastate.edu. FAU - Carpenter, Susan AU - Carpenter S AD - Department of Animal Science, Iowa State University, Ames, IA 50011, USA. scarp@iastate.edu. LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20170516 PL - Switzerland TA - Viruses JT - Viruses JID - 101509722 RN - 0 (Antibodies, Neutralizing) RN - 0 (Antigens, Viral) RN - 0 (RNA, Viral) SB - IM MH - Amino Acid Sequence MH - Animals MH - Antibodies, Neutralizing MH - Antigenic Variation/*genetics/*immunology MH - Antigens, Viral/genetics/immunology MH - Base Sequence MH - Cell Line MH - Disease Models, Animal MH - *Genetic Variation MH - Open Reading Frames/*genetics/*immunology MH - Phenotype MH - Porcine Reproductive and Respiratory Syndrome/blood/*immunology MH - Porcine respiratory and reproductive syndrome virus/*genetics/*immunology MH - RNA, Viral/genetics MH - Sus scrofa MH - Swine MH - Virion MH - Virus Attachment MH - Virus Replication PMC - PMC5454425 OTO - NOTNLM OT - PRRSV OT - antigenic variation OT - genetic diversity OT - neutralization OT - replication phenotype COIS- The authors declare no conflict of interest. EDAT- 2017/05/17 06:00 MHDA- 2018/01/24 06:00 PMCR- 2017/05/01 CRDT- 2017/05/17 06:00 PHST- 2017/03/08 00:00 [received] PHST- 2017/04/18 00:00 [revised] PHST- 2017/04/24 00:00 [accepted] PHST- 2017/05/17 06:00 [entrez] PHST- 2017/05/17 06:00 [pubmed] PHST- 2018/01/24 06:00 [medline] PHST- 2017/05/01 00:00 [pmc-release] AID - v9050113 [pii] AID - viruses-09-00113 [pii] AID - 10.3390/v9050113 [doi] PST - epublish SO - Viruses. 2017 May 16;9(5):113. doi: 10.3390/v9050113.