PMID- 24756023 OWN - NLM STAT- MEDLINE DCOM- 20150120 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 4 DP - 2014 TI - Variation in fetal outcome, viral load and ORF5 sequence mutations in a large scale study of phenotypic responses to late gestation exposure to type 2 porcine reproductive and respiratory syndrome virus. PG - e96104 LID - 10.1371/journal.pone.0096104 [doi] LID - e96104 AB - In spite of extensive research, the mechanisms of reproductive disease associated with Porcine Reproductive and Respiratory Syndrome virus (PRRSv) are still poorly understood. The objectives of this large scale study were to evaluate associations between viral load and fetal preservation, determine the impact of type 2 PRRSv on fetal weights, and investigate changes in ORF5 PRRSv genome in dams and fetuses during a 21-day period following challenge. At gestation day 85 (+/-1), 114 gilts were experimentally infected with type 2 PRRSv, while 19 gilts served as reference controls. At necropsy, fetuses were categorized according to their preservation status and tissue samples were collected. PRRSv RNA concentrations were measured in gilt serum collected on days 0, 2, 6, and 21 post-infection, as well as in gilt and fetal tissues collected at termination. Fetal mortality was 41+/-22.8% in PRRS infected litters. Dead fetuses appeared to cluster in some litters but appeared solitary or random in others. Nine percent of surviving piglets were meconium-stained. PRRSv RNA concentration in fetal thymus, fetal serum and endometrium differed significantly across preservation category and was greatest in tissues of meconium-stained fetuses. This, together with the virtual absence of meconium staining in non-infected litters indicates it is an early pathological condition of reproductive PRRS. Viral load in fetal thymus and in fetal serum was positively associated with viral load in endometrium, suggesting the virus exploits dynamic linkages between individual maternal-fetal compartments. Point mutations in ORF5 sequences from gilts and fetuses were randomly located in 20 positions in ORF5, but neither nucleotide nor amino acid substitutions were associated with fetal preservation. PRRSv infection decreased the weights of viable fetuses by approximately 17%. The considerable variation in gilt and fetal outcomes provides tremendous opportunity for more detailed investigations of potential mechanisms and single nucleotide polymorphisms associated with fetal death. FAU - Ladinig, Andrea AU - Ladinig A AD - Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. FAU - Wilkinson, Jamie AU - Wilkinson J AD - Department of Agricultural, Food, and Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, Edmonton, Alberta, Canada. FAU - Ashley, Carolyn AU - Ashley C AD - Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. FAU - Detmer, Susan E AU - Detmer SE AD - Department of Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. FAU - Lunney, Joan K AU - Lunney JK AD - Animal Parasitic Diseases Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, Maryland, United States of America. FAU - Plastow, Graham AU - Plastow G AD - Department of Agricultural, Food, and Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, Edmonton, Alberta, Canada. FAU - Harding, John C S AU - Harding JC AD - Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140422 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (RNA, Viral) RN - 0 (Viral Envelope Proteins) RN - 0 (glycoprotein 5, PRRSV) SB - IM MH - Abortion, Veterinary/*virology MH - Animals MH - Endometrium/virology MH - Female MH - Fetal Weight MH - Genetic Association Studies MH - Genotype MH - Gestational Age MH - Phenotype MH - Polymorphism, Single Nucleotide MH - Porcine Reproductive and Respiratory Syndrome/mortality/*virology MH - Porcine respiratory and reproductive syndrome virus/*genetics MH - Pregnancy MH - RNA, Viral/genetics MH - Sequence Analysis, DNA MH - Sus scrofa MH - Swine MH - Thymus Gland/virology MH - Viral Envelope Proteins/*genetics MH - Viral Load PMC - PMC3996001 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/04/24 06:00 MHDA- 2015/01/21 06:00 PMCR- 2014/04/22 CRDT- 2014/04/24 06:00 PHST- 2014/02/21 00:00 [received] PHST- 2014/04/03 00:00 [accepted] PHST- 2014/04/24 06:00 [entrez] PHST- 2014/04/24 06:00 [pubmed] PHST- 2015/01/21 06:00 [medline] PHST- 2014/04/22 00:00 [pmc-release] AID - PONE-D-14-04030 [pii] AID - 10.1371/journal.pone.0096104 [doi] PST - epublish SO - PLoS One. 2014 Apr 22;9(4):e96104. doi: 10.1371/journal.pone.0096104. eCollection 2014.