Location: Genetics and Animal Breeding
Title: Host synaptogyrin-2 facilitates replication of PCV2bAuthor
WALKER, LIANNA - University Of Nebraska | |
ENGLE, TAYLOR - University Of Nebraska | |
VU, HEIP - University Of Nebraska | |
TOSKY, EMILY - University Of Nebraska | |
Nonneman, Danny - Dan | |
Smith, Timothy - Tim | |
BORZA, TUDOR - Dalhousie University | |
BURKEY, THOMAS - University Of Nebraska | |
PLASTOW, GRAHAM - University Of Alberta | |
KACHMAN, STEPHEN - University Of Nebraska | |
CIOBANU, DANIEL - University Of Nebraska |
Submitted to: International Society for Animal Genetics (ISAG)
Publication Type: Abstract Only Publication Acceptance Date: 2/28/2019 Publication Date: 7/12/2019 Citation: Walker, L., Engle, T., Vu, H., Tosky, E., Nonneman, D., Smith, T., Borza, T., Burkey, T., Plastow, G., Kachman, S., Ciobanu, D. 2019. Host synaptogyrin-2 facilitates replication of PCV2b [abstract]. In proceedings: 37th International Society for Animal Genetics (ISAG). 7-12 July 2019, Lleida, Spain. pg. 119. Abstract P208. Interpretive Summary: Technical Abstract: Porcine Circovirus 2 (PCV2) is the smallest known virus capable of infecting mammals and the primary agent responsible for a set of symptoms and syndromes known as Porcine Circovirus Associated Diseases. However, infection with PCV2 does not guarantee the onset of clinical disease. Several factors, such as co-infection, are known to influence disease progression, but observed variation in severity between breeds and individuals suggested host genetics may play an important role as well. Genome-wide association analyses of ~1,000 pigs experimentally infected with PCV2b revealed two major QTL for PCV2b viral load, located on host SSC7 and SSC12. A combination of ab initio gene prediction, RNA sequencing, and genomic sequencing identified 66 novel polymorphisms across 5 positional candidate genes within the SSC12 QTL. Single marker association analysis of a subset of pigs with extreme high and low viral loads, identified a novel polymorphism accounting for >20% of the phenotypic variation. This polymorphism is a missense mutation (p.Arg63Cys) located within the second exon of the SYNGR2 gene, which encodes a critical protein domain. In vitro siRNA mediated gene silencing of SYNGR2 in PK15 cells resulted in a one-log reduction in PCV2b titer (P < 0.05) compared to scramble siRNA and non-transfected control cells. Additionally, gene editing using CRISPR-Cas9 ribonucleoprotein complexes generated a PK15 edited clone homozygous for a 106 bp deletion within the second exon of SYNGR2 that exhibited a two-log reduction in PCV2b titer following infection compared to wild-type PK15 cells (P < 0.05). Together, these findings indicate a direct role of SYNGR2 in facilitating PCV2b infection. Because SYNGR2 p.Arg63Cys is the only missense mutation within this gene, SYNGR2 p.Arg63Cys is a plausible QTN for PCV2b susceptibility. |