1. Viral reproductive disorders in sows
an update 2012
H. Nauwynck
Laboratory of Virology
Faculty of Veterinary Medicine
Ghent University, Belgium

2. Normal gestation in the sow
2. Cytokine/growth factor
cross talk
?
1. CL (progesterone)
3. Immune suppression

3. How do viruses cause reproductive problems?
1. General disease (fever) ~ pro-inflammatory cytokines
causing distortion of cytokine balance
-> swine influenza virus, …
2. Replication of pathogens in reproductive
tract/embryo/fetus ~ damaging the placenta and/or
cytokine balance
~ direct negative impact on embryo/fetus
-> DNA viruses: Aujeszky’s disease virus,
parvovirus, porcine circovirus 2
-> RNA viruses: porcine reproductive and respiratory
syndrome virus, porcine enteroviruses,
encephalomyocarditis virus, classical swine fever

4. How do viruses reach embryos/fetuses?
1. Contaminated sperm

5. How do viruses reach embryos/fetuses?
2. Viremia +
transplacental
spread

6. 1. Via contaminated
sperm
Virus excretion in sperm
~ viremia
DNA-viruses Embryo
ADV (<14 dPI) Virus rep & †
PPV (<14 dPI) Virus rep & † repeat breeding
PCV2 (<50 dPI;>) Virus rep & †
RNA-viruses
PRRSV (<50 dPI;>) No virus rep (only infection sow)
PEV (<14 dPI) Virus rep & † repeat breeding
CSFV (<14 dPI) Virus rep & †

7. At what stage can embryos be infected ?
2-8 cells morula blastocyst hatched blastocyst
(0-4dpins) (4-5dpins) (5-7dpins) (>7dpins)
ADV - - - +
PPV - - - +
PCV2 - - - +
PRRSV - - - -
PEV ? ? ? +
CSFV ? ? ? +
Virus should resist aggressive uterine
environment!!!
1° difficult to inactivate: PPV, PCV2, PEV (no

8. Zona pellucida is an ideal barrier
1° Physical barrier
Channels in ZP : ± 30 nm (inner ø)
Viruses > 30nm (ADV, PRRSV, CSFV)
2° Chemical barrier
Viruses < 30nm (PPV, PCV2, PEV)

9. Outcome of embryonic PPV-
infection
Uninfected
PPV-infected

10. Outcome of embryonic PCV2-
infection
Surgical ET
HB 6 dpins
PCV2/mock
Inspection of
ovaries
(follicles/CL)
Euthanasia
D14 post ET
Collection & analysis of embryos

11. Outcome of embryonic PCV2-
Sow infection
Embryos Embryos Ovaries
n° at transfer at euthanasia
n° n° normal degenerated
A statu 19 19 0 CL
B s 17 15 2 CL
26 mock
C 26 mock 13 7 6 CL
D 3 0 3 CL
E 20 0 0 0 follicles
F PCV 0 0 0 follicles
G 2 0 0 0 follicles
23 mock
normal
PCV embryo
2
20 PCV2
PCV degenerated
2 embryo

12. Outcome of embryonic PCV2-
Sow infection
Embryos Embryos Ovaries
n° at transfer at euthanasia
n° n° normal degenerated
A statu 19 19 0 0 CL
B s 17 15 0 2 0 CL
26 mock
C 26 mock 13 74 66 CL
D 3 0 33 CL
E 20 0 0 0 follicles
F PCV 0 0 0 follicles
G 2 0 0 0 follicles
IHC-PCV2
23
PCV
2
20
PCV
2

13. Outcome of embryonic PCV2-
Sow infection
Embryos Embryos Ovaries
n° at transfer at euthanasia
n° n° normal degenerated
A statu 19 19 0 0 CL
B s 17 15 0 2 0 CL
26 mock
C 26 mock 13 74 66 CL
D 3 0 33 CL
E 20 0 0 0 follicles
F PCV 0 0 0 follicles
G 2 0 0 0 follicles
IHC-PCV2
23
PCV2 infection of embryos leads to
PCV
• embryonic death
2
20
• return to oestrus of sow (regular/irregular)
PCV
• both PCV2a and PCV2b
2

14. 2. Viremia + transplacental spread
DNA-viruses
(PPV, PCV2, ADV)
RNA-viruses
(PRRSV, CSFV,
PEV 1, 3, 6 & 8, EMCV)
• Cell-free: PPV, PEV, PRRSV, EMCV
• Cell-associated: ADV, PCV2, CSFV

15. Transplacental
spread -
cell free virus
PRRSV (> 70dpi)
* *
PPV, PEV, EMCV *
* * *

16. Normal
placenta
fetal site
maternal site

17. Transplacental spread - PRRSV - 1. cell free virus + free mø

18. Transplacental spread - PRRSV - 2. cell free virus +
migrating mø

19. Transplacental spread - PRRSV - 3. infection of migrating
mø

20. Transplacental spread - PRRSV - 4. entry of fetal placenta
by migrating mø

21. Transplacental spread - PRRSV - 5. explosive replication in
fetal placental mø

22. Transplacental spread - PRRSV - 6. apoptosis in infected
mø
and bystander cells

23. Transplacental spread - PRRSV - 7. apoptosis in infected
mø
and bystander
cells/necrosis?

24. Transplacental spread - PRRSV - 8. dysfunction placenta

25. Transplacental spread - PRRSV - 8. dysfunction placenta

26. Transplacental
spread -
cell-associated virus
PCV2, ADV, CSFV * * * *
* * *
* * * * *
** * * * *
* * **

27. Cell-associated transplacental spread of ADV
Maternal
placenta
Maternal Fetal
placenta placenta

28. Interfetal virus spread
*

29. Clinical outcome - fetus
Infection time (days of gestation)
0-30 30-60 60-90 90-113
ADV † † † †
PPV † † †/IR IR
PCV2 † † †/IR IR
PRRSV - (†) † †/IR
PEV † † †/IR IR
CSFV † †/IT †/IR †/IR
terato
IR immune response
IT immune tolerance

30. Clinical outcome - sow
Infection time (days of gestation)
0-30 30-60 60-90 90-113
ADV repeat br. abortion abortion abortion/msw
PPV repeat br. msw msw normal
PCV2 repeat br. msw msw normal
PRRSV - - late abortion/msw late abortion/msw
PEV repeat br. msw msw normal
CSFV repeat br. abortion/msw abortion/msw abortion/msw
msw: mummies, stillborn and weakborn piglets at birth

31. ADV

32. PPV
Inoculated po at 47 days of gestation Natural case
Euthanized at 81 days of gestation At birth

33. Inoculated at 43 days of gestation
PPV Euthanized at 98 days of gestation

34. PCV2
Inoculated Aspect Virus Abs Intra-uterine Interruption
(days of gestation) at birth spread of gestation
57 mummified + - + -
75 stillborn
+ + - -
autolytic
92 normal + + - -
mummified autolytic normal

35. PCV2
inoculated at 57 days of gestation
collected at 21 days PI
Ascites,
congestion
of internal organs
Myocarditis At birth
mummified

36. PRRSV

37. PEV
Inoculated in fetus 8
at 59 days of gestation
Hysterectomy at 113 days
of gestation
7 living fetuses

38. CSFV
Inoculation of CSFV (low virulence) po at 43 days of gestation
Collection at parturition

39. Reproductive failure - Diagnosis?
Main complaint: abortion ≠ stages of gestation
Fetuses Fetuses
fresh, rigor mortis (firm) not fresh, partially mummified
Sera sow Lungs/spleen fetuses
(esp. with necrotic foci in liver)
No serum sows!!!
Seroconversion
SIV or other pathogen Immunofluorescence
causing general disease Virus isolation/PCR
fever ADV, CSFV

40. Reproductive failure - Diagnosis?
Main complaint: SMEDI
Fetuses/piglets at birth
Mummies (≠ stages), stillborn and normal piglets
1) Heart/spleen/lungs fetuses (<70 dpins; <17cm)
2) Body fluid/serum fetuses (>70dpins; >17cm)
No serum sows!!!
1) Virus isolation/PCR
2) Antibody detection (BE CAREFULL WITH PCV2!!!)
PPV, PCV2, PEV, EMCV

41. Reproductive failure - Diagnosis?
Main complaint: late abortion/early farrowing
Fetuses at late abortion/early farrowing
Early stages of mummification (brown), stillborn and normal piglets
Placenta/lungs/spleen fetuses
Serum stillborn/piglets before colostrum uptake
No serum sows!!!
Virus isolation(±)/PCR
PRRSV

42. Virus-embryo/fetus work
Laboratory of Virology
& Laboratory of Reproductive Technology
Faculty of Veterinary Medicine
Ghent University, Belgium
H. Nauwynck
A. Van Soom
G. Labarque
R. Sanchez
G. Vanroose
S. Tanghe
B. Mateusen
P. Meerts
D. Lefebvre
D. Saha
U. Karniychuk
I. Trus
J. Beek