Pigs Lacking the Scavenger Receptor Cysteine-Rich Domain 5 of CD163 Are Resistant to Porcine Reproductive and Respiratory Syndrome Virus 1 Infection

Abstract

Porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) is the etiological agent of PRRS, causing late-term abortions, stillbirths, and respiratory disease in pigs, incurring major economic losses to the worldwide pig industry. The virus is highly mutagenic and can be divided into two species, PRRSV-1 and PRRSV-2, each containing several subtypes. Current control strategies mainly involve biosecurity measures, depopulation, and vaccination. Vaccines are at best only partially protective against infection with heterologous subtypes and sublineages, and modified live vaccines have frequently been reported to revert to virulence. Here, we demonstrate that a genetic-control approach results in complete resistance to PRRSV infection in vivo. CD163 is edited so as to remove the viral interaction domain while maintaining protein expression and biological function, averting any potential adverse effect associated with protein knockout. This research demonstrates a genetic-control approach with potential benefits in animal welfare as well as to the pork industry.

Genome editing for disease resistance in pigs and chickens

“…The resulting animals were completely resistant to PRRSV infection and maintained the biological functions associated with the remaining domains of CD163 (Burkard et al, 2017;Burkard et al, 2018).…”

CRISPR in livestock: From editing to printing

“…Based on this information, genome-edited pigs with a disruption in the CD163 gene were produced by CRISPR, conferring resistance to PRRSV infection. CD163 edited piglets, reported in two different projects in US and Scotland, were completely resistant to North American and European PRRSV strains [52,53]. The authors reported that the animals Table 1 Pregnancy outcomes after zygote microinjection with CRISPR/Cas system of in vitro produced embryos transferred fresh or subjected to vitrification in sheep (unpublished data).…”

Molecular and Cellular Mechanisms for PRRSV Pathogenesis and Host Response to Infection

“…With the advance of CRISPR/Cas-based genome editing, specific gene-knockout pigs can be generated rapidly. The studies show that the pigs lacking either CD163 cellular receptor for PRRSV or the scavenger receptor cysteine-rich domain 5 (SRCR5) of CD163 become resistant to both PRRSV-1 and PRRSV-2 infections (Burkard et al, 2018;Prather et al, 2017;Whitworth et al, 2016;Yang et al, 2018). Such a gene-editing technology will allow generating immune-associated gene-deletion phenotypes, and genome-modified pigs will be valuable tools to study the basis for pathogenesis.…”