In the past two decades or so, a number of viruses have emerged in the global swine population. Some, such as porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) cause economically important diseases in pigs, while others such as Torque teno sus virus (TTSuV), porcine bocavirus (PBoV), porcine toroviruses (PToV), and porcine lymphotropic herpesviruses (PLHV) are mostly subclinical in nature in swine herds.

Although some emerging and re-emerging swine viruses such as swine hepatitis E virus (swine HEV) and porcine sapovirus (porcine SaV) may have an unknown clinical implication in swine health, they do pose a human public health concern due to confirmed (swine HEV) or potential (porcine SaV) zoonotic risk.

Swine Hepatitis E Virus (swine HEV)

Since the discovery of swine HEV in 1997 from pigs in the United States (1), the virus has now been identified in swine herds from essentially all swine–producing countries of the world (2). Swine HEV is currently classified in the family of Hepeviridae, which consists of at least four genotypes of human HEV, avian HEV and other animal strains of HEV. Thus far, all swine HEV strains identified from pigs worldwide belong to either genotype 3 or 4, and are genetically closely related to, or in some cases indistinguishable from, genotypes 3 and 4 strains of human HEV (3).

Swine HEV infection is widespread in swine farms worldwide from both developing and industrialised countries, regardless whether HEV is endemic in respective human populations (2). The virus generally infects pigs of two to four months of age with a transient viraemia lasting one to two weeks and faecal virus shedding for about three to seven weeks. Swine HEV infection in pigs is subclinical, although microscopic lesions of hepatitis have been found in both naturally and experimentally infected pigs. Mild to moderate multifocal and periportal lymphoplasmacytic hepatitis were observed in naturally infected pigs. Pigs experimentally infected with swine HEV had mildly to moderately enlarged hepatic and mesenteric lymph nodes, and multifocal lymphoplasmacytic hepatitis and focal hepatocellular necrosis (4).

The major concern currently for swine HEV is zoonotic human infection, pork and environmental safety (5). Hepatitis E is a recognised zoonotic disease, and pigs are reservoirs for genotypes 3 and 4 HEV. Under experimental conditions, genotypes 3 and 4 strains of human HEV infected pigs, and conversely genotypes 3 and 4 strains of swine HEV infected non-human primates. Swine veterinarians and other pig handlers are at increased risks of HEV infection, and individuals from traditionally major swine–producing states in the US are more likely to be positive for HEV antibodies than those from traditionally non–swine States. Approximately 11 per cent of the pig livers sold in grocery stores in USA and two per cent in Japan are positive for HEV RNA and most importantly, the contaminating virus in the commercial pig livers remains infectious. The virus sequences recovered from commercial pig livers are closely related, or identical in a few cases, to the viruses recovered from human hepatitis E patients.

Sporadic cases of acute hepatitis E have been definitely linked to the consumption of contaminated raw and undercooked pork. In France, figatelli pig liver sausages have been identified as the source of sporadic cases of hepatitis E in humans (6). In Japan, cluster cases of acute hepatitis E have been reported in patients who ate swine HEV–infected wild boar meats. As a faecal–orally transmitted disease, contaminated water is the main source of HEV infection.

Pigs infected by swine HEV excreted large amounts of viruses in faeces, which poses a concern for environmental safety. Infectious swine HEV has been detected in swine manure, and in concrete pits and lagoons of swine manure storage facility. Thus, swine manure land application and run–offs could be the source for contamination of irrigation and drinking water or costal water with concomitant contamination of produce or shellfish. Swine HEV was detected in oysters, and consumption of contaminated shellfish has been implicated in sporadic cases of acute hepatitis E (7).

Although swine HEV does not pose a major health concern in pigs, it remains to be determined if concurrent infections of swine HEV with other swine pathogens could have any synergistic effects on pig health. The demonstrated zoonotic, pork and environmental safety risks associated with swine HEV infection in pigs indicate that it is important to eliminate swine HEV from commercial productions.

Torque Teno Sus Virus (TTSuV)

Porcine Torque teno virus (TTV), now known as Torque teno sus virus (TTSuV), was first identified in Japan in 2002 from domestic pigs (8), even though evidence of TTSuV infection was traced back to as early as 1985 in Spain (9). TTSuV is a small single-stranded circular DNA virus in the genus Iotatorquevirus of the family Anelloviridae, which also comprises its homologous counterpart of human TTV. At least two species of TTSuV, TTSuV1 and TTSuV2, have been identified from pigs worldwide.

TTSuV appears to be ubiquitous in both healthy and diseased domestic pigs worldwide (10). Co-infections with TTSuV1 and TTSuV2 at high prevalence rate have been documented in pigs worldwide by using PCR and real-time PCR assays (11-13). By using the putative capsid protein as the ELISA antigen, a high rate of seropositivity to TTSuV2 was detected in conventional pigs of various sources but not in gnotobiotic pigs (14). In general, pigs with undetectable TTSuV2 DNA were more likely to have a lower anti-TTSuV2 antibody level (14). Multiple infections of TTSuV with distinct genotypes or subtypes of the same species in the same pig have also been reported (15).

The pathogenicity of TTSuV in pigs remains debatable. In a gnotobiotic pig model, TTSuV1-containing homogenates partially contribute to the experimental induction of porcine dermatitis and nephropathy syndrome (PDNS) and post–weaning multisystemic wasting syndrome (PMWS) (16-17). In addition, it has been shown that PMWS–affected pigs with low or no detectable PCV2 infection had a higher prevalence of TTSuV2 DNA than non–PMWS–affected pigs in Spain (18) although no significant differences in viral loads of both TTSuV1 and TTSuV2 were found in a small sample size study in Korea between PCV2–negative pigs and PMWS–affected pigs. Interestingly, PMWS–affected pigs had a significantly lower level of TTSuV2 antibody than PMWS–unaffected pigs. Vertical transmission of TTSuV has been reported, however there were no statistically significant differences in TTSuV prevalence between aborted foetuses and foetuses collected at slaughterhouse (19).

The lack of a susceptible cell culture system to propagate TTSuV and the difficulty in obtaining TTSuV negative conventional pigs for research greatly hinder our ability to understand the pathogenicity of TTSuV in pigs. It remains to be determined if TTSuV has any adverse effect on pigs concurrently infected with other swine pathogens.

Porcine Bocavirus (PBoV)

PBoV was discovered in 2008 from pigs in Hong Kong (20), and is genetically related to human parvovirus 4 with approximately 60 per cent nucleotide sequence identity. Approximately 44 per cent of the lymph nodes, liver, serum, nasopharyngeal and faecal samples from pigs in Hong Kong are positive for PHoV DNA. The virus appears to be widespread in swine herds worldwide, and PBoV has been identified from pigs in various countries including Sweden, the United States and China (21). The pathogenicity of PBoV in pigs is unclear. In Sweden, in addition to TTSuV and PCV2, approximately 88 per cent of the PMWS–affected pigs were positive for PBoV DNA, although 46 per cent of the pigs without PMWS are also positive (22). It remains to be determined if PBoV plays any role in pathogenicity during concurrent infections with other swine pathogens.

Porcine Lymphotropic Herpesviruses (PLHV)

In 1999, by using a pan–herpesvirus consensus PCR assay, two closely related gamma–herpesviruses, designated porcine lymphotropic herpesviruses 1 and 2 (PLHV-1 and PLHV-2), were discovered in pigs (23). A third porcine gammaherpesvirus with considerable sequence differences with PLHV-1 and PLHV-2, designated PLHV-3, was identified in 2003 (24). All three viruses were frequently detected in the blood and lymphoid organs of domestic pigs from different geographic regions. Propagation and isolation of PLHV in cell culture are not available. Molecular epidemiological data suggested that PLHV infection is ubiquitous in commercial swine herds, and PLHV DNA was frequently detectable in the blood, spleen and lung tissues. In addition to domestic pigs, PLHV DNA was also detected in high frequency from miniature and feral swine (25).

The pathogenicity of PLHV in pigs under natural conditions remains unclear. It has been reported that PLHV-1 is associated with post–transplant lymphoproliferative disease (PTLD) in miniature pigs following allogeneic haematopoietic stem cell transplantation (26-27).

The clinical symptoms of experimental porcine PTLD, such as fever, lethargy, anorexia, high WBC count and palpable lymph nodes, are similar to those of human PTLD, which was linked to a human gamma-herpesvirus, Epstein-Barr virus. Characteristic gross pathological lesions in PTLD pigs include enlargement of tonsils and lymph nodes. Microscopic lesions include typical polymorphous PTLD cells with a mixture of immunoblasts, plasmacytoid cells and plasma cells in the lymph nodes.

Currently, the main concern for PLHV is the potential risk of human infection in xenotransplantation with pig cells, tissues and organs. Appropriate breeding procedures can eliminate PLHV, and piglets free of PLHV were produced via caesarian-derived and barrier-reared breeding procedure. (28)

Porcine Torovirus (PToV)

PToV was identified in 1998 from piglets in the Netherlands (29), and belongs to the genus Torovirus of the family Coronaviridae in the order Nidovirales. PoTV is genetically related to bovine and equine toroviruses with 60 to 70 per cent sequence identities.

PToV has been identified from piglets in many countries including The Netherlands, Belgium, Hungary, Korea, Spain and Italy (30). Seroprevalence of PToV varied from 50 to 80 per cent, depending on the ages and geographic origins of piglets (29, 31). Piglets shed virus in the faeces for one or more days, starting four to 14 days after weaning (29), and between 19 and 40 per cent of the piglets had faecal virus shedding (32-33). The lack of an in vitro cell culture to propagate PToV hinders our ability to determine the pathogenicity of PToV in pigs, and therefore the pathogenic potential of PToV as diarrhoea–causing agent in pigs remains unclear.

Porcine Sapovirus (Porcine SaV)

Porcine SaV was discovered in 1980 by EM as rotavirus-like and calicivirus-like virus particles associated with piglet diarrhoea (34) and genetic characterisation of the virus in 1999 led to its classification as a sapovirus (35). Porcine Sav belongs to the genus Sapovirus of the Caliciviridae family. At least five distinct genogroups of sapoviruses have been identified: human SaV belongs to GI, GII, GIV, and GV, whereas porcine SaV primarily belongs to GIII although potential new genogroup of porcine SaVs and recombinant SaVs have also been reported in pigs and humans (36-37).

Porcine Sav appears to be widespread in the pig population worldwide, and has been genetically identified from faeces of pigs in numerous countries including United States, Denmark, Finland, Hungary, Venezuela, Italy, Spain, Japan, Slovenia, Canada, Brazil and Korea (38). The prevalence of porcine SaV varied from herds to herds and among different geographic locations with the highest prevalence rate of 62 per cent in the United States (40) and the lowest prevalence rate of two per cent in Hungary (38). The highest prevalence was seen in young piglets of two to eight weeks of ages, and the GIII genogroup is most prevalent (38).

Sapoviruses are associated with diarrhoea in humans and animals (pigs and minks) (36). The Cowden strain of porcine SaV was shown to induce diarrhoea and intestinal lesions in experimentally infected gnotobiotic piglets (40). However, in a recent study, no significant difference was observed in the prevalence of porcine SaV between healthy pigs and pigs with diarrhoea in Spain and Denmark (38).

Definitive evidence of zoonotic human infection by porcine SaVs is still lacking. However, the demonstrated intra–genogroup and inter–genogroup recombination events between sapoviruses raise a potential concern for crossspecies infection (41).

Acknowledgements

Dr. Meng’s research on PRRSV, PCV2, swine HEV, and TTSuV is currently supported by grants from the US National Institutes of Health (R01AI50611, and R01AI74667), U.S. Department of Agriculture (AFRI-2010-03437, CAP- 2008-55620-19132), Pfizer Animal Health Inc, and Boehringer Ingelheim Vetmedica, Inc

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Reference

X.J. Meng. 2011. Emerging and re-emerging viruses in swine. Proceedings of the International Symposium on Emerging and Re-Emerging Diseases in Pigs. Barcelona, Spain.

Further Reading

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You can view the Proceedings of the 6th International Symposium on Emerging and Re-Emerging Pig Diseases by clicking here.

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Find out more information on PMWS by clicking here.

March 2012