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
| Autor: | Rachel Bardot, Maureen A. Kerrigan, Alan J. Mileham, Ying Fang, Raymond R. R. Rowland, Melissa Samuel, Kevin D. Wells, Benjamin R. Trible, Kristin M. Whitworth, Randall S. Prather |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genotype Swine 040301 veterinary sciences Immunology Porcine Reproductive and Respiratory Syndrome Antigens Differentiation Myelomonocytic Receptors Cell Surface Microbiology 0403 veterinary science 03 medical and health sciences Antigens CD Virology Gene Order Macrophages Alveolar Animals Genetic Predisposition to Disease Porcine respiratory and reproductive syndrome virus Protein Interaction Domains and Motifs Scavenger receptor Gene Disease Resistance biology HEK 293 cells 04 agricultural and veterinary sciences Viral Load Porcine reproductive and respiratory syndrome virus biology.organism_classification Phenotype Virus-Cell Interactions Genetically modified organism 030104 developmental biology Genetic Loci Insect Science Host-Pathogen Interactions Mutation CD163 |
| Zdroj: | Journal of Virology. 91 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.01521-16 |
| Popis: | 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. IMPORTANCE Genetic modification of the CD163 gene creates the opportunity to develop production animals that are resistant to PRRS, the costliest viral disease to ever face the swine industry. The results create further opportunities to develop refinements in the modification of CD163 with the goal of making pigs refractory to infection while retaining important CD163 functions. |
| Databáze: | OpenAIRE |
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