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ARS Home » Plains Area » Clay Center, Nebraska » U.S. Meat Animal Research Center » Genetics and Animal Breeding » Research » Publications at this Location » Publication #349096

Research Project: Identifying Genomic Solutions to Improve Efficiency of Swine Production

Location: Genetics and Animal Breeding

Title: Synaptogyrin-2 influences replication of porcine circovirus 2

item WALKER, LIANNA - University Of Nebraska
item ENGLE, TAYLOR - University Of Nebraska
item VU, HIEP - University Of Nebraska
item TOSKY, EMILY - University Of Nebraska
item Nonneman, Danny - Dan
item Smith, Timothy - Tim
item BORZA, TUDOR - University Of Nebraska
item BURKEY, THOMAS - University Of Nebraska
item PLASTOW, GRAHAM - University Of Alberta
item KACHMAN, STEPHEN - University Of Nebraska
item CIOBANU, DANIEL - University Of Nebraska

Submitted to: PLoS Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/9/2018
Publication Date: 10/31/2018
Citation: Walker, L.R., Engle, T.B., Vu, H., Tosky, E.R., Nonneman, D.J., Smith, T.P.L., Borza, T., Burkey, T.E., Plastow, G.S., Kachman, S.D., Ciobanu, D.C. 2018. Synaptogyrin-2 influences replication of porcine circovirus 2. PLoS Genetics. 14(10):e1007750.

Interpretive Summary: Managing Porcine Circovirus 2 (PCV2) associated diseases in the US alone costs the swine industry more than $250 million a year. PCV2 spreads easily from farm to farm, slows the growth rate and affects fertility in infected pigs and can even lead to death. This virus is found on all swine farms in the US, but only a few pigs get sick and show signs of disease. There is no diagnostic test that can identify which pigs will, or will not, show signs of disease after infection with PCV2. As a result, all pigs on a farm need to be vaccinated, which is expensive. This research that included over 1,000 experimentally infected pigs with PCV2, is the largest study ever conducted to understand the role of host genetics in PCV2 related illnesses. We found that pig’s own genetics can impact whether a pig will get sick from PCV2. Specifically, we found a mutation in a gene called SYNGR2 that can influence the ability of the PCV2 virus to multiply, affect pig’s growth and their immune system following infection. This research will aid into the development of genetic tests that would predict which pigs could get sick after infection with PCV2. Early identification of pigs that are susceptible to PCV2 infection will result in an improvement in the general health and welfare of pigs and could have important economic benefits to the US swine industry.

Technical Abstract: Porcine circovirus 2 (PCV2) is a circular single-stranded DNA virus responsible for a group of diseases collectively known as PCV2 Associated Diseases (PCVAD). Variation in the incidence and severity of PCVAD exists between pigs suggesting a host genetic component involved in pathogenesis. A large-scale genome-wide association study of experimentally infected pigs (n = 974), provided evidence of a host genetic role in PCV2 viremia, immune response and growth during challenge. Host genotype explained 64% of the phenotypic variation for overall viral load, with two major Quantitative Trait Loci (QTL) identified on chromosome 7 (SSC7) near the swine leukocyte antigen complex class II locus and on the proximal end of chromosome 12 (SSC12). The SNP having the strongest association, ALGA0110477 (SSC12), explained 9.3% of the genetic and 6.2% of the phenotypic variance for viral load. Dissection of the SSC12 QTL based on gene annotation, genomic and RNA-sequencing, suggested that a missense mutation in the SYNGR2 (SYNGR2 p.Arg63Cys) gene is potentially responsible for the variation in viremia. This polymorphism, located within a protein domain conserved across mammals, results in an amino acid variant SYNGR2 p.63Cys only observed in swine. PCV2 titer in PK15 cells decreased when the expression of SYNGR2 was silenced by specific-siRNA, indicating a role of SYNGR2 in viral replication. Additionally, a PK15 edited clone generated by CRISPR-Cas9, carrying a partial deletion of the second exon that harbors a key domain and the SYNGR2 p.Arg63Cys, was associated with a lower viral titer compared to wildtype PK15 cells (>24 hpi) and supernatant (>48hpi)(P < 0.05). Identification of a non-conservative substitution in this key domain of SYNGR2 suggests that the SYNGR2 p.Arg63Cys variant may underlie the observed genetic effect on viral load.