PMID- 38184111
OWN - NLM
STAT- MEDLINE
DCOM- 20240116
LR  - 20240222
IS  - 1872-9096 (Electronic)
IS  - 0166-3542 (Linking)
VI  - 221
DP  - 2024 Jan
TI  - Genetically modified pigs lacking CD163 PSTII-domain-coding exon 13 are 
      completely resistant to PRRSV infection.
PG  - 105793
LID - S0166-3542(24)00001-9 [pii]
LID - 10.1016/j.antiviral.2024.105793 [doi]
AB  - CD163 expressed on cell surface of porcine alveolar macrophages (PAMs) serves as 
      a cellular entry receptor for porcine reproductive and respiratory syndrome virus 
      (PRRSV). The extracellular portion of CD163 contains nine scavenger receptor 
      cysteine-rich (SRCR) and two proline-serine-threonine (PST) domains. Genomic 
      editing of pigs to remove the entire CD163 or just the SRCR5 domain confers 
      resistance to infection with both PRRSV-1 and PRRSV-2 viruses. By performing a 
      mutational analysis of CD163, previous in vitro infection experiments showed 
      resistance to PRRSV infection following deletion of exon 13 which encodes the 
      first 12 amino acids of the 16 amino acid PSTII domain. These findings predicted 
      that removal of exon 13 can be used as a strategy to produce gene-edited pigs 
      fully resistant to PRRSV infection. In this study, to determine whether the 
      deletion of exon 13 is sufficient to confer resistance of pigs to PRRSV 
      infection, we produced pigs possessing a defined CD163 exon 13 deletion (DeltaExon13 
      pigs) and evaluated their susceptibility to viral infection. Wild type (WT) and 
      CD163 modified pigs, placed in the same room, were infected with PRRSV-2. The 
      modified pigs remained PCR and serologically negative for PRRSV throughout the 
      study; whereas the WT pigs supported PRRSV infection and showed PRRSV related 
      pathology. Importantly, our data also suggested that removal of exon 13 did not 
      affect the main physiological function associated with CD163 in vivo. These 
      results demonstrate that a modification of CD163 through a precise deletion of 
      exon 13 provides a strategy for protection against PRRSV infection.
CI  - Copyright (c) 2024 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Salgado, Brianna
AU  - Salgado B
AD  - Department of Pathobiology, College of Veterinary Medicine, University of 
      Illinois at Urbana-Champaign, Champaign, IL, USA.
FAU - Rivas, Rafael Bautista
AU  - Rivas RB
AD  - Department of Pathobiology, College of Veterinary Medicine, University of 
      Illinois at Urbana-Champaign, Champaign, IL, USA.
FAU - Pinto, Derek
AU  - Pinto D
AD  - Department of Pathobiology, College of Veterinary Medicine, University of 
      Illinois at Urbana-Champaign, Champaign, IL, USA.
FAU - Sonstegard, Tad S
AU  - Sonstegard TS
AD  - Acceligen, Eagan, Minnesota, USA.
FAU - Carlson, Daniel F
AU  - Carlson DF
AD  - Acceligen, Eagan, Minnesota, USA.
FAU - Martins, Kyra
AU  - Martins K
AD  - Acceligen, Eagan, Minnesota, USA.
FAU - Bostrom, Jonathan R
AU  - Bostrom JR
AD  - Acceligen, Eagan, Minnesota, USA.
FAU - Sinebo, Yamlak
AU  - Sinebo Y
AD  - Acceligen, Eagan, Minnesota, USA.
FAU - Rowland, Raymond R R
AU  - Rowland RRR
AD  - Department of Pathobiology, College of Veterinary Medicine, University of 
      Illinois at Urbana-Champaign, Champaign, IL, USA.
FAU - Brandariz-Nunez, Alberto
AU  - Brandariz-Nunez A
AD  - Department of Pathobiology, College of Veterinary Medicine, University of 
      Illinois at Urbana-Champaign, Champaign, IL, USA. Electronic address: 
      brandari@illinois.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20240104
PL  - Netherlands
TA  - Antiviral Res
JT  - Antiviral research
JID - 8109699
SB  - IM
MH  - Swine
MH  - Animals
MH  - *Porcine respiratory and reproductive syndrome virus/genetics
MH  - *Porcine Reproductive and Respiratory Syndrome/genetics
MH  - Macrophages, Alveolar
MH  - Gene Editing/methods
MH  - Exons
OTO - NOTNLM
OT  - Antiviral breeding
OT  - CD163
OT  - Exon 13
OT  - Gene-edited pigs
OT  - PRRSV
OT  - PSTII
COIS- Declaration of competing interest The authors declare the following financial 
      interests/personal relationships which may be considered as potential competing 
      interests:The work is in support of an ongoing U.S. patent application.
EDAT- 2024/01/07 06:44
MHDA- 2024/01/16 06:42
CRDT- 2024/01/06 19:14
PHST- 2023/11/13 00:00 [received]
PHST- 2023/12/18 00:00 [revised]
PHST- 2024/01/02 00:00 [accepted]
PHST- 2024/01/16 06:42 [medline]
PHST- 2024/01/07 06:44 [pubmed]
PHST- 2024/01/06 19:14 [entrez]
AID - S0166-3542(24)00001-9 [pii]
AID - 10.1016/j.antiviral.2024.105793 [doi]
PST - ppublish
SO  - Antiviral Res. 2024 Jan;221:105793. doi: 10.1016/j.antiviral.2024.105793. Epub 
      2024 Jan 4.