Synaptogyrin-2 influences replication of Porcine circovirus 2

Lianna R. Walker, Taylor B. Engle, Hiep L Vu, Emily R. Tosky, Dan J. Nonneman, Timothy P.L. Smith, Tudor Borza, Thomas E Burkey, Graham S. Plastow, Stephen D Kachman, Daniel C Ciobanu

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere1007750
JournalPLoS genetics
Volume14
Issue number10
DOIs
StatePublished - Oct 1 2018

Fingerprint

Synaptogyrins
Circovirus
Porcine circovirus-2
viral load
Viral Load
pig
swine
Swine
chromosome
Quantitative Trait Loci
Viremia
viremia
phenotypic variation
quantitative trait loci
Clustered Regularly Interspaced Short Palindromic Repeats
gene
ssDNA viruses
dissection
circular DNA
antigen

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Walker, L. R., Engle, T. B., Vu, H. L., Tosky, E. R., Nonneman, D. J., Smith, T. P. L., ... Ciobanu, D. C. (2018). Synaptogyrin-2 influences replication of Porcine circovirus 2. PLoS genetics, 14(10), [e1007750]. https://doi.org/10.1371/journal.pgen.1007750

Synaptogyrin-2 influences replication of Porcine circovirus 2. / Walker, Lianna R.; Engle, Taylor B.; Vu, Hiep L; Tosky, Emily R.; Nonneman, Dan J.; Smith, Timothy P.L.; Borza, Tudor; Burkey, Thomas E; Plastow, Graham S.; Kachman, Stephen D; Ciobanu, Daniel C.

In: PLoS genetics, Vol. 14, No. 10, e1007750, 01.10.2018.

Research output: Contribution to journalArticle

Walker, LR, Engle, TB, Vu, HL, Tosky, ER, Nonneman, DJ, Smith, TPL, Borza, T, Burkey, TE, Plastow, GS, Kachman, SD & Ciobanu, DC 2018, 'Synaptogyrin-2 influences replication of Porcine circovirus 2', PLoS genetics, vol. 14, no. 10, e1007750. https://doi.org/10.1371/journal.pgen.1007750
Walker LR, Engle TB, Vu HL, Tosky ER, Nonneman DJ, Smith TPL et al. Synaptogyrin-2 influences replication of Porcine circovirus 2. PLoS genetics. 2018 Oct 1;14(10). e1007750. https://doi.org/10.1371/journal.pgen.1007750
Walker, Lianna R. ; Engle, Taylor B. ; Vu, Hiep L ; Tosky, Emily R. ; Nonneman, Dan J. ; Smith, Timothy P.L. ; Borza, Tudor ; Burkey, Thomas E ; Plastow, Graham S. ; Kachman, Stephen D ; Ciobanu, Daniel C. / Synaptogyrin-2 influences replication of Porcine circovirus 2. In: PLoS genetics. 2018 ; Vol. 14, No. 10.
@article{a19fc078713a44df8b80492a64094edd,
title = "Synaptogyrin-2 influences replication of Porcine circovirus 2",
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.",
author = "Walker, {Lianna R.} and Engle, {Taylor B.} and Vu, {Hiep L} and Tosky, {Emily R.} and Nonneman, {Dan J.} and Smith, {Timothy P.L.} and Tudor Borza and Burkey, {Thomas E} and Plastow, {Graham S.} and Kachman, {Stephen D} and Ciobanu, {Daniel C}",
year = "2018",
month = "10",
day = "1",
doi = "10.1371/journal.pgen.1007750",
language = "English (US)",
volume = "14",
journal = "PLoS Genetics",
issn = "1553-7390",
publisher = "Public Library of Science",
number = "10",

}

TY - JOUR

T1 - Synaptogyrin-2 influences replication of Porcine circovirus 2

AU - Walker, Lianna R.

AU - Engle, Taylor B.

AU - Vu, Hiep L

AU - Tosky, Emily R.

AU - Nonneman, Dan J.

AU - Smith, Timothy P.L.

AU - Borza, Tudor

AU - Burkey, Thomas E

AU - Plastow, Graham S.

AU - Kachman, Stephen D

AU - Ciobanu, Daniel C

PY - 2018/10/1

Y1 - 2018/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85056419795&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056419795&partnerID=8YFLogxK

U2 - 10.1371/journal.pgen.1007750

DO - 10.1371/journal.pgen.1007750

M3 - Article

VL - 14

JO - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7390

IS - 10

M1 - e1007750

ER -