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

Kevin D. Wells, Rachel Bardot, Kristin M. Whitworth, Benjamin R. Trible, Ying Fang, Alan Mileham, Maureen A. Kerrigan, Melissa S. Samuel, Randall S. Prather, Raymond R.R. Rowland

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article numbere01521-16
JournalJournal of virology
Volume91
Issue number2
DOIs
StatePublished - 2017
Externally publishedYes

Keywords

  • CD163
  • Genetic modification
  • Porcine reproductive and respiratory syndrome virus

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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