PMID- 26961593 OWN - NLM STAT- MEDLINE DCOM- 20170926 LR - 20180420 IS - 1567-7257 (Electronic) IS - 1567-1348 (Linking) VI - 40 DP - 2016 Jun TI - ORF5 of porcine reproductive and respiratory syndrome virus (PRRSV) is a target of diversifying selection as infection progresses from acute infection to virus rebound. PG - 167-175 LID - S1567-1348(16)30072-7 [pii] LID - 10.1016/j.meegid.2016.03.002 [doi] AB - 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. CI - Copyright (c) 2016 Elsevier B.V. All rights reserved. FAU - Chen, Nanhua AU - Chen N AD - 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. FAU - Trible, Benjamin R AU - Trible BR AD - Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, United States. FAU - Kerrigan, Maureen A AU - Kerrigan MA AD - Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, United States. FAU - Tian, Kegong AU - Tian K AD - OIE Porcine Reproductive and Respiratory Syndrome Reference Laboratory, Beijing, PR China. FAU - Rowland, Raymond R R AU - Rowland RRR AD - Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, United States. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160304 PL - Netherlands TA - Infect Genet Evol JT - Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases JID - 101084138 RN - 0 (RNA, Viral) RN - 0 (Viral Envelope Proteins) RN - 0 (glycoprotein 5, PRRSV) SB - IM MH - Amino Acid Sequence MH - Amino Acid Substitution MH - Animals MH - Disease Progression MH - Genetic Variation MH - Genome, Viral MH - Neutralization Tests MH - Porcine Reproductive and Respiratory Syndrome/*virology MH - Porcine respiratory and reproductive syndrome virus/*genetics/immunology MH - RNA, Viral MH - *Selection, Genetic MH - Sequence Analysis, DNA MH - Swine MH - Time Factors MH - Viral Envelope Proteins/chemistry/*genetics MH - Viral Load MH - Viremia OTO - NOTNLM OT - Deep sequencing OT - Diversifying selection OT - Porcine reproductive and respiratory syndrome virus (PRRSV) OT - Viral quasispecies OT - Virus rebound EDAT- 2016/03/11 06:00 MHDA- 2017/09/28 06:00 CRDT- 2016/03/11 06:00 PHST- 2016/01/30 00:00 [received] PHST- 2016/02/28 00:00 [revised] PHST- 2016/03/02 00:00 [accepted] PHST- 2016/03/11 06:00 [entrez] PHST- 2016/03/11 06:00 [pubmed] PHST- 2017/09/28 06:00 [medline] AID - S1567-1348(16)30072-7 [pii] AID - 10.1016/j.meegid.2016.03.002 [doi] PST - ppublish SO - Infect Genet Evol. 2016 Jun;40:167-175. doi: 10.1016/j.meegid.2016.03.002. Epub 2016 Mar 4.