Pigs with CD163 Mutation Conferred PRRSV Resistance

TL;DR

Scientists created pigs that are resistant to a costly viral disease by editing a key protein, CD163, which the virus needs to infect them.

Contribution

The study demonstrates that pigs with a CD163 mutation are completely resistant to PRRSV infection in vivo.

Findings

CD163−/− pigs showed no signs of infection after exposure to PRRSV, unlike normal pigs.

PRRSV could not replicate in CD163−/− pigs, confirming CD163 as essential for viral entry.

The edited pigs had no lung or organ damage, while control pigs had severe lesions.

Abstract

Pig farmers worldwide lose billions of dollars each year due to a viral disease called PRRS, which causes breathing problems and reproductive failure in pigs. The virus enters pig cells by attaching to a specific protein called CD163. In this study, we used gene editing technology to create pigs that lack CD163. When we exposed these edited pigs to the PRRS virus, they remained completely healthy, while normal pigs became severely ill with lung damage. This proves that CD163 is essential for the virus to infect pigs. These virus-resistant pigs could help farmers reduce disease outbreaks, decrease antibiotic use, and improve animal welfare, offering a sustainable solution for pork production.

Porcine reproductive and respiratory syndrome (PRRS), which is caused by the porcine reproductive and respiratory syndrome virus (PRRSV), results in substantial economic losses for the global pig farming industry. A critical step in the infection process is the binding of PRRSV to the CD163 receptor on the surface of porcine alveolar macrophages. This study successfully generated CD163−/− Landrace pigs using CRISPR/Cas9 gene editing technology. Following an experimental challenge with two distinct Type II PRRSV strains, the edited pigs exhibited complete resistance to infection. Virological and pathological examinations confirmed the absence of viral replication and the presence of characteristic pulmonary lesions and other organ damage in CD163−/− pigs. In contrast, wild-type control pigs exhibited high viral loads and severe pulmonary lesions, as well as damage to other organs. Our findings provide direct evidence that CD163 is an essential receptor for PRRSV infection in vivo. The CD163−/− pig model offers an effective genetic strategy for breeding pigs with an inherent resistance to PRRSV.

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