Genetics of Host Resistanceto PRRS and PCV2

Jack Dekkers 

Department of Animal ScienceIowa State University

Porcine Reproductive and Respiratory Syndrome - PRRS

Sows Abortions Stillborn/weak pigs Delayed estrus Respiratory

problems

Grower Increased

mortality Decreased

production Respiratory

problems

Large financial loss in both production settings

Respig.com Respig.com

Eradication Biosecurity Vaccination Host genetics

Strategies tocontrol PRRS

ObjectiveUse genomics to identify genes / genomic regions associated with

resistance / susceptibility to PRRS virus infection

Led byJoan Lunney – USDA – ARS Beltsville

Bob Rowland – Kansas State UniversityJim Reecy & Jack Dekkers – Iowa State University

Strong Industry ParticipationPHGC Breeding Companies

Fast Genetics, Genesus, Choice GeneticsPIC/Genus, TOPIGS, PigGen Canada

60 k SNP chipIllumina

GeneSeek2007

Iowa State UniversityNick Boddicker Andrew Hess Emily Waide,

Jenelle Dunkelberger Eric Fritz-WatersJames Koltes, Martine Schroyen Nick SeraoJim Reecy Chris Tuggle Susan Carpenter

Kansas State UniversityBob Rowland PRRS group

Ben Trible, Megan Niederwerder Maureen KerriganUSDA-ARS

Joan Lunney group, Igseo Choi, Sam AbramsUniversity of AlbertaGraham Plastow groupUniv. SaskatchewanJohn Harding group

Roslin InstituteSteve Bishop Andrea Doeschl-Wilson

Zeenath Islam Graham LoughUniv. Minnesota

Monserat Torremorrell, Bob Morrison

Scientific Collaborators

Integrated International Interdisciplinary Projects

Nursery PigChallenge Model

WeightSerum

SlaughterEar for DNA

-7 0 7 11 14 21 35 424 28

SerumAntibiotics

Acclimation

Birth WeightSerum

Inoculation

WeightSerum

WeightSerum

WeightSerum

WeightSerum

WeightSerum

Serum Serum

Day post infection

R.R.R. Rowland et al., Kansas State UniversityGroups of ~200 commercial crossbred pigs infected with

PRRS virus isolate NVSL97-7985 between 18 and 28 d of age

2304 challenged pigs with deep phenotypes

and genotypes

PHGC PRRS trialsGeneration 1 & 2

Host ResponsePhenotypes

Body weight Log(viremia)

Rebound

Viral LoadArea Under Curve

h2 = 0.41h2 = 0.29rp = -0.25 rg = -0.47

VIRAL LOAD WEIGHT GAIN

Major QTL for host response to PRRS on SSC 4

Boddicker et al. 2012, 2014a,b; Hess et al. 2015

0 5 10 15 20 25 30 35 400

1

2

3

4

5

6

7

Viremia NVSL AA

Viremia NVSL AB

Days Post Infection

Log

10(V

irem

ia)

0 5 10 15 20 25 30 35 400

1

2

3

4

5

6

7

Viremia KS06 AA

Viremia KS06 AB

Days Post InfectionL

og10

(Vir

emia

)

Hess et al. 2015

Major QTL for host response to PRRS on SSC 4

0 5 10 15 20 25 30 35 400

1

2

3

4

5

6

7

0

5

10

15

20

25

Viremia NVSL AAViremia NVSL ABWeight NVSL AAWeight NVSL AB

Days Post Infection

Log

10(V

irem

ia)

Wei

ght (

kg)

0 5 10 15 20 25 30 35 400

1

2

3

4

5

6

7

0

5

10

15

20

25

Viremia KS06 AAViremia KS06 ABWeight KS06 AAWeight KS06 AB

Days Post InfectionL

og10

(Vir

emia

)

Wei

ght (

kg)

Hess et al. 2015

Major QTL for host response to PRRS on SSC 4

AA pigs Truncated GBP5 protein PI3K-Akt pathway not turned off

See Poster by Martine Schroyen et al.A Hypothesis

Genomic regions do not overlap between isolates but GO-term pathways do

KS06

NVSL WUR = 21

WUR = 7WUR = 7

WUR = 21

See Poster by Emily Waide et al.

Identification of otherhost response QTL

Viral Load

rg(NVSL, KS06) = 0.86 (+0.19)

KS06

NVSL WUR = 16WUR = 16

Weight Gain

rg(NVSL, KS06) = 0.86 (+0.27)

See Poster by Emily Waide et al.

Identification of otherhost response QTL

Estimate SNP

effectsSNPGenotypes

Phenotypes

SNPGenotypes

Genomic Prediction

Training population

Validation population

PhenotypesCorrelate

Genomic PredictionPrediction using high-density SNPs

KS06 NVSL

Can we use GenomicPrediction across isolates?NVSL Trials

KS06 Trials

17

r/h

Waide et al. 2015

Total PRRS Antibody Responseat day 42

MHC Class I

MHC Class II

Two SNPs in MHC explain 15 and 30% of genetic varianceNo association with WUR SNP on SSC4

h2 = 13%

(Hess, Trible et al.)

NVSL KS060.4

0.6

0.8

1

1.2Cleared Rebound Persistent

S:P

ratio a b a a

ba

Relationship of PRRS Ab at 42 dpiwith serum viremia profiles

Hess et al. 2014

5 10 15 20 25 30 35 40-1

-0.6

-0.2

0.2

0.6

1

Days Post Infection

NVSL Viremia

5 10 15 20 25 30 35 40-1

-0.6

-0.2

0.2

0.6

1

Days Post Infection

KS06 Viremia

5 10 15 20 25 30 35 40-1

-0.6

-0.2

0.2

0.6

1

Days Post Infection

NVSL Weight Gain

5 10 15 20 25 30 35 40-1

-0.6

-0.2

0.2

0.6

1

Days Post Infection

KS06 Weight Gain

Phenotypic corr.Genetic correlation

Correlations of S:P at 42 dpi with viremia and weight gain (Andrew Hess)

See Poster by Andrew Hess

Association of Tonsil viremiawith serum viremial profile

Jack Dekkers, Chris TuggleJim Reecy, Ken Stalder

Robert RowlandYongming Sang

Joan LunneyMontse Torremorell

Robert MorrisonSteve Bishop, David Hume

Andrea Doeschl-Wilson

Translational Genomics USDA-NIFA grant # 2013-68004-20362

3rd Generation PRRS Challenge StudiesCo-infection and Field Studies

Genetically Improving Resistance of Pigsto PRRS Virus Infections

Translational Genomics USDA-NIFA grant # 2013-68004-20362

Outreach Obj. 3Education Obj. 4

Educate industry stakeholders and next generation of industry leaders

Arr

ive

Vacc

i-na

te

Days postvaccination -1 0 4 7 11 14 21 28 32 35 39 42 49 56 63 70

Days post infection 0 4 7 11 14 21 28 35 42

Infe

ct

Vaccination response Vaccination + infection responseEarly response Later response

Body weight and Blood samples

80k SNPgenotypes

Obj.1 Vaccination & Co-infection TrialsExperimental design

4 groups of 200 commercial crossbred piglets (18-21 d)

50 AA Vaccinated (PRRS MLV) 50 AB50 AA Non-vaccinated 50 AB

WUR WUR

Co-infection with PRRSv and PCV2 PCVAD

Seru

m

Days post 0 7 14 21 28 42 60 90 Market arrival

FMIA and SNA

Seru

mSe

rum

Seru

m

Seru

m

Wei

ght

Wei

ght

Wei

ght

Wei

ght

BF,

LEA

Body weightPen oral fluids for disease surveillance purposes on all days indicated

SNA on all oral fluid samples

29

Obj.2 Field Challenge Trials Experimental design

6 groups of 200 commercial crossbred piglets (18-21 d)

100 AA 100 ABWUR WUR

Moved into health-challenged barns

SNPgenotypes

PrePRRS VL

PRRS VL

Pre ADG

Post ADG

PCV2b VL

___ = AA Non Vx___ = AB Non Vx___ = AA Vx___ = AB Vx

Co-

infe

ctio

n

PRRS viremia

Co-

infe

ctio

nC

o-in

fect

ion Body weight PCV2b viremia

Results 2 co-infection Trials

Vacc

inat

ion

Vacc

inat

ion

See Poster by Jenelle Dunkelberger et al.

PrePRRS VL

PRRS VL

Post ADG

Co-

infe

ctio

n

PRRS viremia

Co-

infe

ctio

n

PCV2b VL

Vacc

inat

ion

Pre ADG

Co-

infe

ctio

n

Vacc

inat

ion

___ = AA Non Vx___ = AB Non Vx___ = AA Vx___ = AB Vx

Results 2 co-infection Trials

PrePRRS VL

PRRS VL

Post ADG

PCV2b VL

Co-

infe

ctio

n

Co-

infe

ctio

n Results 2 co-infection Trials

Vacc

inat

ion

Pre ADG

Co-

infe

ctio

n

Vacc

inat

ion

6 0 8 0 1 0 0 1 2 0

3 0

4 0

5 0

6 0

7 0

8 0

9 0

1 0 0

f(x) = 0.2534995727812 x + 31.456703872604R² = 0.0713522979744744

Pre-Infection

Post

-Infe

c-tio

n

Post- vs. Pre-PRRS VL

Dunkelberger (2015)

33

8,74 16,86

2,284,139

(WUR) 7,24(MHC)

4,1367,40 12,4

Genome Wide Association Studies

See poster Jenelle Dunkelberger

Conclusions• Vaccination-co-infection design is good model for PCVAD • PRRSV vaccination amplification of PCVAD reduced growth• SSC4 QTL had a larger effect on PRRS viremia with

primary exposure to PRRS innate immune function.• SSC4 QTL affected PCV2b viremia but only after PRRS

vaccination• PRRS and PCV2b viremia controlled by different

genomic regions with versus without vaccination.

opportunities to select vaccine-ready pigs?

May 23-27, 2016, Iowa State University

Dr. Andrea Doeschl-Wilson, Univ. Edinburgh2014 course

Disease Genetics: From Concepts to UtilizationProf. Steve Bishop, Univ. Edinburgh

Disease Genetics Short CourseMathematical modelling of Infection Dynamics

Iowa State UniversityNick Boddicker Andrew Hess Emily Waide,

Jenelle Dunkelberger Eric Fritz-WatersJames Koltes, Martine Schroyen Nick SeraoJim Reecy Chris Tuggle Susan Carpenter

Kansas State UniversityBob Rowland PRRS group

Ben Trible, Megan Niederwerder Maureen KerriganUSDA-ARS

Joan Lunney group, Igseo Choi, Sam AbramsUniversity of AlbertaGraham Plastow groupUniv. SaskatchewanJohn Harding group

Roslin InstituteSteve Bishop Andrea Doeschl-Wilson

Zeenath Islam Graham LoughUniv. Minnesota

Monserat Torremorrell, Bob Morrison

Scientific Collaborators