PMID- 27847356
OWN - NLM
STAT- MEDLINE
DCOM- 20170515
LR  - 20190329
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 91
IP  - 2
DP  - 2017 Jan 15
TI  - Replacement of Porcine CD163 Scavenger Receptor Cysteine-Rich Domain 5 with a 
      CD163-Like Homolog Confers Resistance of Pigs to Genotype 1 but Not Genotype 2 
      Porcine Reproductive and Respiratory Syndrome Virus.
LID - 10.1128/JVI.01521-16 [doi]
LID - e01521-16
AB  - CD163 knockout (KO) pigs are resistant to infection with genotype 2 (type 2) 
      porcine reproductive and respiratory syndrome virus (PRRSV). Furthermore, the 
      substitution of CD163 scavenger receptor cysteine-rich (SRCR) domain 5 with a 
      homolog of human CD163-like (hCD163L1) SRCR 8 domain confers resistance of 
      transfected HEK cells to type 1 PRRSV. As a means to understand the role of 
      domain 5 in PRRSV infection with both type 1 and type 2 viruses, pigs were 
      genetically modified (GM) to possess one of the following genotypes: complete 
      knockout (KO) of CD163, deletions within SRCR domain 5, or replacement (domain 
      swap) of SRCR domain 5 with a synthesized exon encoding a homolog of hCD163L1 
      SRCR domain 8. Immunophenotyping of porcine alveolar macrophages (PAMs) showed 
      that pigs with the KO or SRCR domain 5 deletion did not express CD163. When 
      placed in culture, PAMs from pigs with the CD163 KO phenotype were completely 
      resistant to a panel consisting of six type 1 and nine type 2 isolates. PAMs from 
      pigs that possessed the hCD163L1 domain 8 homolog expressed CD163 and supported 
      the replication of all type 2 isolates, but no type 1 viruses. Infection of 
      CD163-modified pigs with representative type 1 and type 2 viruses confirmed the 
      in vitro results. The results confirm that CD163 is the likely receptor for all 
      PRRS viruses. Even though type 1 and type 2 viruses are considered phenotypically 
      similar at several levels, there is a distinct difference between the viral 
      genotypes in the recognition of CD163. IMPORTANCE: Genetic modification of the 
      CD163 gene creates the opportunity to develop production animals that are 
      resistant to PRRS, the costliest viral disease to ever face the swine industry. 
      The results create further opportunities to develop refinements in the 
      modification of CD163 with the goal of making pigs refractory to infection while 
      retaining important CD163 functions.
CI  - Copyright (c) 2017 American Society for Microbiology.
FAU - Wells, Kevin D
AU  - Wells KD
AD  - Division of Animal Science, College of Food Agriculture and Natural Resources, 
      University of Missouri, Columbia, Missouri, USA.
FAU - Bardot, Rachel
AU  - Bardot R
AD  - Department of Diagnostic Medicine and Pathobiology, College of Veterinary 
      Medicine, Kansas State University, Manhattan, Kansas, USA.
FAU - Whitworth, Kristin M
AU  - Whitworth KM
AD  - Division of Animal Science, College of Food Agriculture and Natural Resources, 
      University of Missouri, Columbia, Missouri, USA.
FAU - Trible, Benjamin R
AU  - Trible BR
AD  - Department of Diagnostic Medicine and Pathobiology, College of Veterinary 
      Medicine, Kansas State University, Manhattan, Kansas, USA.
FAU - Fang, Ying
AU  - Fang Y
AD  - Department of Diagnostic Medicine and Pathobiology, College of Veterinary 
      Medicine, Kansas State University, Manhattan, Kansas, USA.
FAU - Mileham, Alan
AU  - Mileham A
AD  - Genus, PLC, DeForest, Wisconsin, USA.
FAU - Kerrigan, Maureen A
AU  - Kerrigan MA
AD  - Department of Diagnostic Medicine and Pathobiology, College of Veterinary 
      Medicine, Kansas State University, Manhattan, Kansas, USA.
FAU - Samuel, Melissa S
AU  - Samuel MS
AD  - Division of Animal Science, College of Food Agriculture and Natural Resources, 
      University of Missouri, Columbia, Missouri, USA.
FAU - Prather, Randall S
AU  - Prather RS
AD  - Division of Animal Science, College of Food Agriculture and Natural Resources, 
      University of Missouri, Columbia, Missouri, USA.
FAU - Rowland, Raymond R R
AU  - Rowland RRR
AD  - Department of Diagnostic Medicine and Pathobiology, College of Veterinary 
      Medicine, Kansas State University, Manhattan, Kansas, USA 
      browland@vet.k-state.edu.
LA  - eng
PT  - Journal Article
DEP - 20170103
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation, Myelomonocytic)
RN  - 0 (CD163 antigen)
RN  - 0 (Receptors, Cell Surface)
SB  - IM
MH  - Animals
MH  - Antigens, CD/chemistry/*genetics/metabolism
MH  - Antigens, Differentiation, Myelomonocytic/chemistry/*genetics/metabolism
MH  - Disease Resistance/*genetics
MH  - Gene Order
MH  - Genetic Loci
MH  - *Genetic Predisposition to Disease
MH  - *Genotype
MH  - Host-Pathogen Interactions/genetics
MH  - Macrophages, Alveolar/immunology/metabolism/virology
MH  - Mutation
MH  - Phenotype
MH  - Porcine Reproductive and Respiratory Syndrome/*genetics/metabolism/*virology
MH  - Porcine respiratory and reproductive syndrome virus/*physiology
MH  - Protein Interaction Domains and Motifs/*genetics
MH  - Receptors, Cell Surface/chemistry/*genetics/metabolism
MH  - Swine
MH  - Viral Load
PMC - PMC5215333
OTO - NOTNLM
OT  - CD163
OT  - genetic modification
OT  - porcine reproductive and respiratory syndrome virus
EDAT- 2016/11/17 06:00
MHDA- 2017/05/16 06:00
PMCR- 2017/07/03
CRDT- 2016/11/17 06:00
PHST- 2016/07/29 00:00 [received]
PHST- 2016/11/02 00:00 [accepted]
PHST- 2016/11/17 06:00 [pubmed]
PHST- 2017/05/16 06:00 [medline]
PHST- 2016/11/17 06:00 [entrez]
PHST- 2017/07/03 00:00 [pmc-release]
AID - JVI.01521-16 [pii]
AID - 01521-16 [pii]
AID - 10.1128/JVI.01521-16 [doi]
PST - epublish
SO  - J Virol. 2017 Jan 3;91(2):e01521-16. doi: 10.1128/JVI.01521-16. Print 2017 Jan 
      15.