Pathogenesis and control of Senecavirus A in swine

Authors: Buckley, Alexandra

Submitted to: Iowa State University, Ames, Thesis
Publication Type: Other
Publication Acceptance Date: 11/25/2020
Publication Date: 1/16/2021
Citation: Devries, A.C. 2021. Pathogenesis and control of Senecavirus A in swine. Iowa State University, Ames, Thesis. https://doi.org/10.31274/etd-20210114-20.
DOI: https://doi.org/10.31274/etd-20210114-20

Interpretive Summary: Senecavirus A (SVA) was originally discovered as a cell culture contaminant in 2002, but similar picorna-like viruses had been found in swine samples in the US dating back to the 1980s. These isolates came from swine with various clinical histories, and experimental inoculation with swine did not result in specific clinical disease. SVA was detected sporadically until late 2014, when outbreaks of vesicular disease and neonatal mortality in Brazil had samples test positive for SVA. Similar cases appeared in the US in 2015, and experimental inoculation with contemporary SVA isolates were successful in reproducing vesicular lesions supporting SVA as a causative agent for vesicular disease in swine. The main objective of this research was to better understand the pathogenesis of SVA in swine. The inability to reproduce clinical disease during initial attempts to experimentally infect swine with SVA led to speculation about the requirement of a co-factor or pathogenicity differences between strains. The early clinical history of lesions in pigs during marketing and traveling to fairs in the US drove our hypothesis that stress may exacerbate clinical disease in swine. To simulate stress, an immunosuppressive dexamethasone regime was administered to 9-week-old pigs prior to SVA inoculation. Clinical disease was similar between dexamethasone treated pigs and non-treated pigs. In addition, viremia, viral shedding, and neutralizing antibody response was similar between groups. Thus, this study supported that stress was not required for lesion development and provided information about infection dynamics that could be used by veterinarians and producers to develop strategies for diagnostics and control of SVA in the field. To further explore infection dynamics and pathogenicity of different SVA strains, three historical isolates and three contemporary isolates were selected for comparison. There were some apparent differences in timing of lesion development, viremia, and viral shedding, but all viruses replicated and caused vesicular disease in pigs. Serum from all pigs had cross-neutralizing antibodies against all viruses in the study; but, cross-neutralizing titers against historical isolates were lower than contemporary isolates. Sequence analysis of the six isolates in this study showed amino acid changes in prominent loop structures of the capsid that may play a role in the differences observed in cross-neutralizing titers. The study was the first to demonstrate that the original cell culture contaminant SVA isolate could cause vesicular disease in swine. Experimental animal infections often use high titers of inoculum to ensure consistent replication of disease. Therefore, experimental infections may not be reflective of titers of virus swine are exposed to in the field. To better understand pathogenesis of SVA at different inoculum dosages and the infectious dose of SVA, serial hundred-fold dilutions and ten-fold dilutions of SVA were used to inoculate finishing pigs and neonates, respectively. In this study, with a 2011 SVA isolate, finishing pigs had a MID of 103.1 TCID50/mL and neonates 102.5 TCID50/mL. Although the MID for finishing pigs was higher in this study, the use of hundred-fold dilutions for inoculums provided a less precise estimate compared to the ten-fold dilutions used for neonates. This study also provided insight into the correlation of PCR Ct values with viral titers in cell culture and infectivity in swine. For example, swabs from vesicular lesions can contain titers of 106 TCID50/mL, so contact with a vesicle could expose pigs to virus concentrations 3 logs higher then what is necessary to infect a finishing pig. Vaccines play a critical role in the control and prevention of many veterinary diseases. The type of vaccine to be used is dependent on many factors that include safety, efficacy, and economy. In

Technical Abstract: Senecavirus A (SVA) is a nonenveloped, single-stranded, positive-sense RNA virus in the family Picornaviridae. It was first discovered as a cell culture contaminant in 2002 but had been identified in US swine samples dating back to the late 1980s. Since swine were presumed to be the natural host, pigs were experimentally inoculated, but did not develop any specific clinical disease. Prior to 2015, SVA was sporadically detected in US swine associated with various clinical histories. In 2015, cases of vesicular disease and increased neonatal mortality were observed in Brazil and subsequently in the US. SVA was consistently detected in affected animals. Although previous attempts to reproduce disease with SVA in the past were unsuccessful, experimental inoculation studies performed with contemporary isolates demonstrated SVA was a causative agent for vesicular disease in swine. SVA is now included in the differential list of etiologic agents that can cause vesicular disease in swine. This list includes foot-and-mouth disease virus (FMDV), which is a notifiable disease, so when vesicular lesions are observed in FMDV-free countries an investigation must be initiated to rule out FMDV. SVA has now been found across the Americas and Asia, and it appears the ecology of this virus has changed from sporadic infections to an endemic disease that does not induce severe clinical disease; but, its presence does have a significant impact since each case needs to be investigated as if it was a FMDV case. Thus, control and prevention measures are critical to reducing the spread of SVA in the global swine industry. Due to the difficulty of reproducing clinical disease in past experimental challenges and the timing of SVA outbreaks in the field with stressful situations, there was speculation that stress may be a factor in the development of vesicular lesions. To study the impact of stress, an immunosuppressive dexamethasone regime prior to SVA inoculation was administered. Clinical presentation and infection dynamics were similar in pigs treated with dexamethasone and those not treated prior to challenge. Another hypothesis for the lack of lesions in early experimental challenges was older isolates were less pathogenic than contemporary isolates. Vesicular lesion development and viral shedding in swine were compared between three SVA strains isolated prior to the 2015 outbreak and three strains isolated during 2015. The majority of animals in all groups developed vesicular lesions, and serum had cross neutralizing titers against all viruses. Sequencing and analysis of isolates used in the study found amino acid differences between the isolates in prominent loop structures of the capsid that may be involved with virus receptor binding and host immune response. Due to the clinical similarities between SVA and FMDV, control and prevention of SVA infections are a priority. Understanding the minimum infectious dose (MID) of SVA could provide insights into the infectivity of virus found in the environment and how the virus is spread. Finishing pigs and neonates were used to determine the MID of a 2011 SVA isolate using intranasal and oral challenge routes respectively. In this study, finishing pigs had a MID of 103.1 TCID50/mL and neonates 102.5 TCID50/mL. Although there were differences in infectious dose, fewer dilutions were tested in finishing pigs, which may provide a less precise estimate compared to the neonates. Another control measure for SVA could be vaccination. An inactivated vaccine was tested in weaned pigs and mature sows. The vaccine prevented the development of clinical signs and viremia as well as reduced rectal shedding in pigs. In addition, piglets suckling immunized dams had sterilizing immunity against SVA challenge. Overall, a better understanding of the pathogenesis of SVA in swine can help improve control and prevention measur