Seneca Valley virus disease is a viral vesicular disease of pigs caused by a picornavirus related to the viruses that cause foot-and-mouth disease and swine vesicular disease. Clinically affected pigs develop cutaneous vesicular lesions, mainly on the snout and coronary bands. Seneca Valley virus disease is important as a differential diagnosis for high-consequence transboundary animal diseases, including foot-and-mouth disease, swine vesicular disease, and vesicular exanthema of swine, from which it is clinically indistinguishable.
Seneca Valley virus disease (formerly known as porcine idiopathic vesicular disease) is a viral vesicular disease of pigs.
The causative virus was originally described in 2002 as a contaminant in the cultivation of adenovirus-5-based vectors in the cell line PER.C6. It was named Seneca Valley virus after Seneca Creek State Park in Maryland, near the laboratories that discovered the virus. The virus was speculated to be a contaminant derived from fetal bovine serum or porcine trypsin. Later, sequencing of picornavirus-like particles isolated from swine indicated that porcine trypsin media was more likely to be the source of the virus.
Etiology and Pathogenesis of Seneca Valley Virus Disease in Pigs
Senecavirus A (SVA), commonly known as Seneca Valley virus, is a nonenveloped, positive-sense single-stranded RNA virus of the genus Senecavirus, family Picornaviridae. This family also includes foot-and-mouth disease virus (FMDV) and swine vesicular disease virus.
Initially, SVA was detected only by PCR assay in association with cases of vesicular disease. Not until September 2015 was SVA demonstrated to be present and replicating within vesicular lesions, via an in situ hybridization assay targeting viral VP1 mRNA to define the SVA replication site in tissues. Vesicular lesions were reproduced in animals following inoculation and the virus re-isolated, providing confirmatory evidence for a causal relationship. The infection dynamics revealed an early neutralizing antibody response, short-term viremia, and virus shedding (oral, nasal, and fecal) detected up to 28 days after inoculation.
SVA establishes persistent infections, with viral RNA found in lymphoid tissues such as the tonsils of convalescent animals.
Epidemiology of Seneca Valley Virus Disease in Pigs
Hosts: Neutralizing antibodies to SVA have been detected in swine, cattle, mice, and humans. SVA nucleic acids have been detected in mice and houseflies in addition to pigs. Mink have been infected experimentally.1
Geographic Distribution: Historically, SVA was sporadically detected by PCR assay in cases of porcine idiopathic vesicular disease in the US and Canada. A retrospective serosurvey shows that SVA has been circulating in pigs since at least 1988.2 Cases of idiopathic vesicular disease have also been reported in swine in Australia, New Zealand, and Italy; however, SVA was not specifically investigated. In all of these cases, the differential diagnoses of other vesicular diseases (eg, foot-and-mouth disease, vesicular stomatitis, vesicular exanthema of swine, and swine vesicular disease) were ruled out on the basis of laboratory investigations.
In November 2014, SVA started being detected by PCR assay in cases of neonatal mortality and vesicular disease in Brazil, and it was transmitted rapidly throughout large swine production systems.3 This emerging epidemic scenario in South America differed from the historical data recorded in the US. The National Veterinary Services Laboratories documented ~20 SVA isolates from case submissions dating from between 1988 and 2012, including idiopathic vesicular disease, lameness, and neonatal mortality. In July 2015, commercial swine herds in large integrated systems in the US started experiencing similar epidemic scenarios of vesicular disease and neonatal mortality associated with the detection of SVA by PCR assay. Subsequently, cases of SVA also started emerging in Canada, China, Mexico, and Colombia. SVA cases have now been reported in several states in the US, ranging from major swine production operations in the Midwest to the Hawaiian Islands.
Incubation Period: Pigs experimentally infected with SVA start developing vesicular lesions 3–5 days after exposure.
Mortality Rate: A high mortality rate in piglets in the first week of life (referred to as epidemic transient neonatal losses) has been associated with a high load of SVA in tissues.
Transmission: Transmission routes for SVA are not well understood. Given that it is related to FMDV, SVA is thought to spread via direct contact with infected swine, fomites, or exposure to aerosolized virus. How long persistently infected animals carry the virus and their role in the transmission and maintenance of SVA in the swine population remain to be elucidated.
Public Health Relevance: SVA infections are clinically indistinguishable from high-consequence transboundary animal diseases, including foot-and-mouth disease, vesicular stomatitis, vesicular exanthema of swine, and swine vesicular disease. Outbreaks have resulted in major economic impacts associated with temporary closure of pork processing plants until a foreign animal disease incursion is ruled out, reallocation of resources for diagnostic investigation of foot-and-mouth disease and other vesicular diseases, death of neonatal piglets, and increased culling rates in affected sows.
There is no record of SVA causing symptomatic human disease. The first isolated Senecavirus strain (designated SVV-001) has been studied in human medicine for cancer treatment because of its oncolytic properties against small-cell lung cancer, neuroendocrine tumors, and other cancers. The medical literature has suggested a potential selective ability of SVV-001 to infect, replicate, and produce cytotoxicity in cancer cells without consequentially damaging normal tissues. However, neutralizing antibodies induced after the first exposure may impair the oncolytic competence of SVV-001 such that it does not efficiently replicate and lyse tumor cells in a second exposure.
References
Chen C, Nai Z, Wang Y, et al. Isolation and characterization of Seneca Valley virus spread from pig to mink. Authorea. March 30, 2022. doi:10.22541/au.164865127.72529652/v1
Segalés J, Barcellos D, Alfieri A, Burrough E, Marthaler D. Senecavirus A: an emerging pathogen causing vesicular disease and mortality in pigs? Vet Pathol. 2016;54(1):11-21. doi:10.1177/0300985816653990
Vannucci FA, Linhares DC, Barcellos DE, Lam HC, Collins J, Marthaler D. Identification and complete genome of Seneca Valley virus in vesicular fluid and sera of pigs affected with idiopathic vesicular disease, Brazil. Transbound Emerg Dis. 2015;62(6):589-593. doi:10.1111/tbed.12410
Clinical Findings of Seneca Valley Virus in Pigs
Animals clinically affected by Seneca Valley virus develop cutaneous vesicular lesions (fluid-filled and ruptured vesicles or ulcerative lesions), mainly on the snout and coronary bands as well as the interdigital spaces. Other signs include lameness, anorexia, lethargy, cutaneous hyperemia, and fever. The main clinical signs of SVA infection are similar to the lesions observed in pigs with foot-and-mouth disease, vesicular stomatitis, vesicular exanthema of swine, and swine vesicular disease. In pigs experimentally infected with SVA, lesions resolve by day 8–10 after infection.
In neonates, SVA infection can lead to weakness, lethargy, neurologic signs, and diarrhea. A high viral load in tissues is associated with a high mortality rate in piglets in the first week of life (epidemic transient neonatal losses). Clinical signs usually subside within 3–10 days, and most piglets recover completely.
Animals housed in a continuous-flow system (as opposed to all-in all-out management) or without proper disinfection between batches tend to have recurrent clinical signs and to develop chronic and secondary infections in vesicular lesions in the coronary bands.
Lesions
Lesions associated with Seneca Valley virus include vesicular lesions on the snout, coronary bands, interdigital spaces, lips, and tongue. Petechial hemorrhages of the kidney and ulcerative lesions of the tongue and coronary band have been reported. In neonates, diarrhea has been reported in many cases; however, it has not been directly associated with SVA infection in the GI tract. It seems to be more a secondary consequence of the viremia. Subcutaneous and mesenteric edema has been found in piglets with diarrhea.
Diagnosis of Seneca Valley Virus in Pigs
PCR assay
Histopathologic findings
PCR assays on samples from vesicular lesions, feces, oral swabs, oral fluids, or tissue homogenate taken from neonatal piglets can confirm a diagnosis of Seneca Valley virus. In situ hybridization assays can demonstrate the presence of the virus associated with vesicular lesions in formalin-fixed tissues.
Differential diagnoses include foot-and-mouth disease, vesicular stomatitis, vesicular exanthema of swine, swine vesicular disease, and noninfectious, localized causes, such as blisters due to mechanical, chemical, or thermal lesions.
Treatment, Control, and Prevention of Seneca Valley Virus in Pigs
No specific treatment
General biosecurity measures
No specific treatment is available for Seneca Valley virus infections.
General biosecurity measures are important to mitigate direct transmission. An important characteristic of SVA is its extended persistence in the environment. Cleaning and disinfection with hydrogen peroxide and bleach can inactivate the virus. Managers of sow farms have been successful with a protocol of herd closure and deliberate virus exposure, using fecal samples, tissues, or vesicular fluid from infected animals.
Multiple vaccines have been evaluated for efficacy against SVA.1,2
References
Buckley A, Lager K. Efficacy of an inactivated Senecavirus A vaccine in weaned pigs and mature sows. Vaccine. 2022;40(12):1747-1754. doi:10.1016/j.vaccine.2022.02.018
Sharma B, Fernandes MHV, de Lima M, Joshi LR, Lawson S, Diel DG. A novel live attenuated vaccine candidate protects against heterologous senecavirus A challenge. Front Immunol. 2019;10:2660. doi:10.3389/fimmu.2019.02660
Key Points
Vesicular disease that is due to Senecavirus A is indistinguishable from foot-and-mouth disease.
The virus can persist in tonsils and can be found in semen for several weeks in convalescent animals.
Senecavirus A is very stable in the environment; hydrogen peroxide and bleach can inactivate it.
References
Segalés J, Barcellos D, Alfieri A, Burrough E, Marthaler D. Senecavirus A: an emerging pathogen causing vesicular disease and mortality in pigs? Vet Pathol. 2016;54(1):11-21. doi:10.1177/0300985816653990
Joshi L, Fernandes M, Clement T, et al. Pathogenesis of Senecavirus A in finishing pigs. Gen Virol. 2016;97(12):3267-3279. doi:10.1099/jgv.0.000631
Resende TP, Marthaler DG, Vannucci FA. A novel RNA-based in situ hybridization to detect Seneca Valley virus in neonatal piglets and sows affected with vesicular disease. PLoS One. 2017;12(4):e0173190. doi:10.1371/journal.pone.0173190
Burke MJ. Oncolytic Seneca Valley virus: past perspectives and future directions. Oncolytic Virother. 2016;5:81-89. doi:10.2147/OV.S96915
