Porcine parvoviruses

Attila Cságola

Department of Microbiology and Infectious Diseases Family Subfam. Genus Parvovirus Chicken parvovirus (Galliform aveparvovirus 1) (Protoparvovirus) Feline panleukopenia (Carnivore protoparvovirus 1) Feline panleukopenia virus 2 Mink enteritis virus Racoon parvovirus Porcine parvovirus (Ungulate protoparvovirus 1) Etc Erythrovirus Human parvovirus B19 (Primate erythroparvovirus 1) (Erythroparvovirus) Bovine parvovirus type 3 (Ungulate erythroparvovirus 1) Dependovirus Adeno associated virus (Adeno-associated dependoparvovirus) (Dependoparvovirus) Goose parvovirus (Anseriform dependoparvovirus 1) Duck parvovirus (Anseriform dependoparvovirus 1) Amdovirus Aleutian mink disease virus (Carnivore amdoparvovirus 1) (Amdoparvovirus) Bocavirus Bovine parvovirus (Ungulate bocaparvovirus 1) (Bocaparvovirus) Human bocaviruses (Primate bocaparvovirus 1, 2) Canine minute virus (Carnivore bocaparvovirus 1) Porcine bocaviruses (Ungulate bocaparvovirus 2-5) Subfam Densovirinae Genus Densovirus Iteravirus Brevidensovirus Pefudensovirus PORCINE PARVOVIRUS DISEASE

Porcine parvovirus 1 (PPV1)

History: 1965: Dunne, SMEDI (Stillbirth, Mummification, Embryonic Death, Infertility) 1967: not enterovirus but parvovirus

Prevalence: Everywhere, wherever pigs are present Less frequent in Australia and New Zealand

Epidemiology: Infected pig: feces and saliva fomites, wind, can survive more than 4 months Boars (and infected sperm) Pathogenesis : P.os

Lymphoid tissues around throat Small intestine

Viraemia transient, symptomless

http://allategeszsegugy.pfizer.hu/images2/pig_parvovirus_okozta_szaporo_2.jpg Pigs Pregnant sow

Immune suppression Lymphoid organs Fetus (2 weeks after the infection)

Co-infection with PCV2: more Pregnant sows: frequent and severe postweaning return to estrus (3-8 weeks after breeding) abortus, smaller than normal litters multisystemic wasting syndrome, Embryo and fetus: (PPV unlikely if at least 8 live pigs) PMWS to 30 days death, resorption Rarely respiratory and 30-70 days death of fetus, mummification vesicular disease in adults, calcification of bones after 35 days, cannot be resorbed systemic disease of neonates. from day 70 weak and mummified fetus active immunity initiated after day 70 New antigenic variant of PPV1: PPV-27a

Originally 1 serotype (PPV1): SMEDI, vaccines (NADL-2 and IDT strains) 2001-PPV1a (PPV-27a): Germany, limited cross-protection with vaccine strains

ZEEUW, E.J., LEINECKER, N., HERWIG, V., SELBITZ, H.J., TRUYEN, U., 2007. Study of the virulence and cross- neutralization capability of recent porcine parvovirus field isolates and vaccine in experimentally infected pregnant gilts. J. Gen. Virol. 88, 420–427.:

„Cross-neutralization of the sera raised against the vaccine viruses PPV-NADL-2 and PPV-IDT (MSV) against the field isolates PPV-143a and PPV-27a as well as against PPV-Challenge (Engl.) revealed low neutralization activity (0.5–0.69) against PPV-27a, indicating incomplete protection. Neutralizing antibodies are known to play a prominent role in protection against parvovirus infection. Therefore, if PPV-27a is representative for current PPV-isolates in the population, this indicates that vaccines, which have been used for 30 years, may no longer be fully protective. Beside the evidence for distinct antigenic types of PPV, another interesting phenomenon became obvious in this study. Interestingly, all sera raised against the field isolate PPV-27a neutralized all heterologous PPV isolates with high efficiency (2.99–3.99), but homologous neutralization was much less efficient (0.69–1.19). This was seen for all three pigs inoculated as well as with the sera of both rabbits immunized with PPV-27a.” WB-716 1 225b 0,94 143a 1h 15425 0,96 WB-773 Tornau 106b 693a 1g 0,91 JY 1 14a WB-631 15a PPV1 21a 27a 0,97 3h WB-533 PPV1a 6R 1d 3a 0,95 7a 8a WB-701 WB-748 0,94 WB-75 4 WB-687 0,96 6a 4e 2g WB-639 WB-613 0,95 WB-72 0,97 ZJ LZ WB-143 BQ 1f WB-802 WB-804 0,90 Kresse (1985) Challenge VRI-1 Nanjing 0,98 NADL-2 (1976) 318 POVCAP Cadar et al., 2012 0,95 POVG SR1 N

(a) 125,0 100,0 75,0 50,0 25,0 0,0 PPV1 HUN

∑ PPV1 HUN strain is genetically, antigenetically highly similar to PPV-27a.

∑ PPV1 HUN strain was isolated from a newborn piglet, originate from a Hungarian swine herd.

∑ In this swine herd, piglets had weak viability (poorly developed piglets, poor resistance, increased mortality).

∑ Gilts and sows were vaccinated against porcine parvovirus.

• PPV1 HUN strain was isolated on Swine testicular cell line (STC).

8 • PPV1 HUN strain can replicate up to 10 tissue culture infective dose 50% (TCID 50 ).

• PPV1 HUN strain is under patenting process. Examination of the PPV1 serological profile of infected swine herds

15-15 serum samples were collected from:

• 2, 7, 14 and 21 days old piglets (60 samples) and their sows (20 samples),

• and 15-15 samples from 28, 36, 43, 57, 90, 120 and 150 days old growing and finishing pigs. Herd A Herd B 5000 6000 4500 4000 5000 3500 4000 3000 2500 3000 2000 1500 2000 1000 1000 500 0 0

Herd C Herd D 12000 8000 10000 7000 6000 8000 5000 6000 4000 4000 3000 2000 2000 1000 0 0 Conclusions

‹ The PPV1 infection causes severe economic losses, so an appropriate and effective protection against PPV1 is highly important.

‹ The maternal antibodies are already absent around 1-2 months of age, but because of infection induced specific humoral immune response, high PPV1 specific antibody level was detected in some individuals of older age groups.

‹ The swine herds, in terms of protection against PPV1, are heterogeneous (which is also true for sows!), which favors the survival and spreading of the virus within the herds.

‹ Vaccines against PPV1 are routinely used in most swine herds. Usually the recommended vaccination time is around the age of 6 months. Our results suggest that the modification of PPV1 vaccination protocol (for example vaccination at 6-8 weeks of age) could be necessary to establish homogeneous immune status of the animals in order to have a more effective defense. Emerging porcine parvoviruses

PPV2 (Ungulate tetraparvovirus 3): 2001: single positive case (Myanmar) 2010: Very high number of cases, China 2011: 6,4% Europe

PPV3 (Ungulate tetraparvovirus 2): HoKovirus, respiratory signs (human Parv4 and 5) 2008-: 3-35% Hong Kong, Great Brittan, Transylvania, Hungary

PPV4 (Ungulate copiparvovirus 2) : Reproductive disorders 2005-: low prevalence but up to 50 within herd 2011: 6,4% Hungary (Europe)

Bocaviruses (Ungulate bocaparvovirus 2-5):

PBoV-like : respiratory in piglets 2009: 0,1% Sweden 2010-: 1,5% Hungary / Europe

Since 2010: PBoV-1, PBoV-2, PBoV-3, PBoV-4, 6V , 7V 88 JF512472.1 Porcine bocavirus 3 ir 99 NC 016031.Porcine bocavirus 3 100 NC 016032.1| Porcine bocavirus 4-1 52 JF713715.1| Porcine bocavirus 3 strain 23 Parvoviruses 90 JF512473.1 Porcine bocavirus 4 ir 100 NC 016647.1| Porcine bocavirus 5 kínai 92 JN681175.1 Porcine bocavirus 3 kínai

99 HM053694.1| Porcine bocavirus 2 100 HM053693.1 Porcine bocavirus 1 75 DQ335247.1| Bovine parvovirus-1 Boca viruses HQ223038.1 Pbo-likeV Feline bocavirus strain 97 100 93 JN648103.1| Canine bocavirus 33 FJ899734.1| Canine minute JQ814850.1| Myotis myotis bocavirus 1

100 NC 012729.2| Human bocavirus 4 93 |FJ375129.1| Human bocavirus

100 HM132056.1| Human bocavirus 3

100 FJ695472.1| Human bocavirus 3 NC 014358.1| Bocavirus gorilla

40 FJ410797.2| Penaeus monodon hepatopancreatic parvovirus 100 NC 014357.1| Fenneropenaeus chinensis hepatopancreatic densovirus NC 007218.1| Penaeus merguiensis densovirus NC 001662.1| Aleutian mink disease virus 91 60 M19296.1 Canine parvovirus 2 100 98 EF988660.1 Feline parvovirus FJ592174.1| Mink enteritis virus strain PPV1, other well known 100 NC 001718 Porcine parvovirus 1 X01457.1| Parvovirus h-1 84 canine, feline, mink parvoviruses 100 U12469.1 Mouse parvovirus 1 26 J02275.1

100 JF333590.1| Goose parvovirus strain 100 NC 006147.2| Muscovy duck parvovirus NC 006148.1| Snake parvovirus 1

100 AF162273.1| Erythrovirus B19 86 U26342.1| Simian parvovirus 39 AF406967Bovine parvovirus 3 NC 016752.1| Artibeus jamaicensis parvovirus 1

79 100 GU214705.1| Turkey parvovirus 98 GU214704.1| Chicken parvovirus Newly described GQ387499.1 Porcine parvovirus 4 80 98 100 JX896320 Porcine parvovirus 5 NC 006259 Bovine parvovirus 2 90 AB076669.1 Porcine parvovirus 2 NC 016744.1| Eidolon helvum parvovirus 1 99 100 HQ113143.1| Human parvovirus 4 100 DQ873391.1human5

97 EU200674 Porcine parvovirus 3 (hokovirus) 0,2 99 EU200668 Bovine hokovirus 91 JF504702.1 Ovine hokovirus Myanmar-type Cnvirus-type threshold d d Cnvirus-type antigens.

Respiratory signs Days of age of Days Sows 2 7 14 21 28 36 43 57 90 120 150 0

0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 Absorbance PPV2 specific antibody profile with Myanmar-type an PPV2with specificantibodyMyanmar-type profile