Deletion of maternal CD163 PSTII-domain-coding exon 13 protects fetuses from infection with porcine reproductive and respiratory syndrome virus (PRRSV)

Vet Microbiol. 2024 Nov:298:110255. doi: 10.1016/j.vetmic.2024.110255. Epub 2024 Sep 23.

Abstract

Following infection of a porcine dam with PRRSV around 90 days of gestation, the virus crosses the placenta and starts to infect fetuses. This can lead to consequences such as abortions, stillbirths, and respiratory issues in newborn piglets. CD163 is an essential cellular viral entry receptor for porcine reproductive and respiratory syndrome virus (PRRSV). CD163 contains nine scavenger receptor cysteine-rich (SRCR) and two proline-serine-threonine (PST) domains. Gene-edited pigs possessing a complete deletion of CD163 are resistant to PRRSV infection. Recently, we demonstrated that pigs harboring a clean deletion of CD163 exon 13 (ΔExon13 CD163 pigs) which encodes the first 12 amino acids of the CD163 PSTII domain were not susceptible to PRRSV infection. In this study, ΔExon13 CD163 (-/-) gilts were bred with wildtype CD163 (+/+) boars producing heterozygous, CD163 (+/-) fetuses. We found that fetuses with a wildtype CD163, recovered between day 103 of gestation or 17 days after the maternal infection with PRRSV, were fully protected from PRRSV in dams containing a clean deletion of CD163 exon 13. These findings suggest a feasible approach for eliminating PRRSV-related reproductive illness, which is a significant cause of economic losses in agriculture.

Keywords: Antiviral breeding; CD163; Exon 13; Gene-edited pigs; PRRSV; PSTII.

MeSH terms

  • Animals
  • Antigens, CD* / genetics
  • Antigens, Differentiation, Myelomonocytic* / genetics
  • CD163 Antigen
  • Exons* / genetics
  • Female
  • Fetus* / virology
  • Porcine Reproductive and Respiratory Syndrome* / immunology
  • Porcine Reproductive and Respiratory Syndrome* / prevention & control
  • Porcine Reproductive and Respiratory Syndrome* / virology
  • Porcine respiratory and reproductive syndrome virus* / genetics
  • Porcine respiratory and reproductive syndrome virus* / immunology
  • Pregnancy
  • Receptors, Cell Surface* / genetics
  • Sequence Deletion
  • Swine

Substances

  • CD163 Antigen
  • Antigens, Differentiation, Myelomonocytic
  • Receptors, Cell Surface
  • Antigens, CD