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2018 Annual Report
Accomplishments
1. Safe Foot-and-Mouth Disease vaccine. Currently, production of Foot and Mouth Disease (FMD) vaccines relies on the use of live virulent virus that can escape manufacturing facilities and cause outbreaks. Live FMD virus is not allowed on the U.S. mainland. Recently, ARS researchers in Orient Point, New York used reverse genetics to create an attenuated FMD virus that is innocuous to animals but can be safely used for vaccine manufacturing. Secretary of Agriculture has authorized the movement of this modified, non-virulent version of the FMD virus from the Plum Island Animal Disease Center to the U.S. mainland for the purposes of continued vaccine development and eventually manufacturing. Vaccine manufacturer Zoetis Inc. requested and has been granted a license for this vaccine technology. Identifying a vaccine that uses a modified virus will enable vaccine manufacturing in the USA and will allow the USDA-APHIS to more quickly source and acquire FMD vaccine for the Strategic Veterinary Stockpile and in the event of an outbreak of this devastating disease.
2. Understanding the mechanisms of the Foot-and-Mouth Disease virus (FMDV) carrier state in cattle. Control and eradication of foot-and-mouth disease (FMD) is impeded by the existence of a prolonged persistent phase of infection in ruminant species which is generally referred to as the FMDV carrier state. Researchers at ARS in Orient Point, New York have spent much of the last 10 years characterizing the mechanisms of persistence in the nasopharynx (throat) of cattle. Now we have taken that information and shown that clearance of FMDV infection was associated with activation of anti-viral T cell responses, whereas the antibody-mediate immune response was stronger in animals that maintained persistent infection. Additionally, mechanisms associated with programmed cell killing (apoptosis) were activated in animals that cleared infection whereas pathways associated with prolonged cell survival were upregulated in FMDV carriers. These findings are critically important for design of novel FMD vaccines that may prevent the occurrence of persistent FMDV infection. The study was published in Scientific Reports.
3. New rapid diagnostic Kit for Foot-and-Mouth Disease. Current foot-and-mouth disease virus (FMDV) vaccines are compatible with a strategy based on “differentiating infected from vaccinated animals” (DIVA). ARS researchers at Orient Point, New York as part of a large research consortium of federal agencies, academia and animal health industry, developed and licensed a rapid-response (three-hour) Foot-and-Mouth Disease (FMD) diagnostic kit. A manuscript describing the validation of this assay that led to the licensure of the FMD diagnostic kit was published in the Journal of Veterinary Diagnostic Investigation.
4. Increased the knowledge about Foot-and-Mouth Disease virus (FMDV) emergence and transmission. Although foot-and-mouth disease (FMD) is widely described as the most important disease affecting international trade in animal products, many aspects of the natural cycle of the causative virus remain unknown. ARS researchers in Orient Point, New York have been working for several years to develop research partnerships in endemic areas of Asia and Africa to describe the behavior of FMDV under natural conditions. Some of these studies have recently culminated with critical findings from work in India which have quantitated the speed of spread of FMDV through herds of cattle during outbreaks, and the duration that the virus persists in those herds. Similarly, ARS researchers performed a study in Cameroon which demonstrated that there are benefits to introducing vaccines to herds of cattle, even if the virus is already present. Additionally, genetic sequences were acquired from viruses discovered in Vietnam which helped to show how the virus evolves over time and space to continuously create new viruses. These findings are critically important to understand how FMDV spreads within the current disease range, and to prepare for the possibility of an outbreak in the USA.
5. Understanding the virus factors critical for Foot-and-Mouth Disease Virus (FMDV) replication. ARS researchers in Orient Point, New York have used novel approaches to derive attenuated FMDV strains using modifications at the 5’terminus of the viral genome. In proof of concepts studies identified a new role attributed to a small segment of the beginning of the FMDV genome that is responsible for virus replication and also modulating the innate immune response in animals to the virus. This knowledge of the virus-unique replication processes has potential for the development of disease control strategies such as better vaccines.
Review Publications
Stenfeldt, C., Eschbaumer, M., Smoliga, G.R., Rodriguez, L.L., Zhu, J.J., Arzt, J. 2017. Clearance of a persistent Picornavirus infection is associated with enhanced pro-apoptotic and cellular immune responses. Scientific Reports. 7:17800. https://doi.org/10.1038/s41598-017-18112-4.
Kloc, A., Rai, D.K., Rieder, A.E. 2018. The roles of picornavirus untranslated regions in infection and innate immunity. Frontiers in Microbiology. 20(9):485. https://doi.org/10.3389/fmicb.2018.00485.
Stenfeldt, C., Arzt, J., Pacheco, J., Gladue, D.P., Smoliga, G.R., Silva, E., Rodriguez, L.L., Borca, M.V. 2018. A partial deletion within foot-and-mouth disease virus non-structural protein 3A causes clinical attenuation in cattle but does not prevent subclinical infection. Virology. 516:115-126. https://doi.org/10.1016/j.virol.2018.01.008.
Kenney, M.A., Waters, R.A., Rieder, A.E., Pega, J., Perez-Filguera, M., Golde, W.T. 2017. Enhanced sensitivity in detection of antiviral antibody responses using biotinylation of foot-and-mouth disease virus (FMDV) capsids. Journal of Immunological Methods. 450:1-9. https://doi.org/10.1016/j.jim.2017.07.001.
Rekant, S., Lyons, M., Pacheco Tobin, J., Arzt, J., Rodriguez, L.L. 2016. Veterinary applications of infrared thermography. American Journal of Veterinary Research. 77:98-107. https://doi.org/10.2460/ajvr.77.1.98.
Ahmed, Z., Pauszek, S.J., Ludi, A., Larocco, M.A., Khan, E., Afzal, M., Arshed, M.J., Farooq, U., Arzt, J., Bertram, M., Brito, B., Naeem, K., Abubakar, M., Rodriguez, L.L. 2017. Genetic diversity and comparison of diagnostic tests for characterization of foot-and-mouth disease virus strains from Pakistan 2008-2012. Transboundary and Emerging Diseases. 65(2):534-546. https://doi.org/10.1111/tbed.12737.
Brito, B.P., Pauszek, S.J., Hartwig, E.J., Smoliga, G.R., Vu, L.T., Vu, P.P., Stenfeldt, C., Rodriguez, L.L., King, D.P., Knowles, N.J., Bachanek-Bankowska, K., Long, N.T., Dung, D.H., Arzt, J. 2018. A traditional evolutionary history of foot-and-mouth disease viruses in Southeast Asia challenged by analyses of non-structural protein coding sequences. Scientific Reports. 8:6472. https://doi.org/10.1038/s41598-018-24870-6.
Bertram, M.R., Delgado, A., Pauszek, S.J., Smoliga, G.R., Brito, B.P., Stenfeldt, C., Hartwig, E.J., Dickmu-Jumbo, S., Abdoulmoumini, M., Abona Olivia, A., Salhine, R., Rodriguez, L.L., Gerabed, R., Arzt, J. 2018. Effect of vaccination on cattle herds previously exposed to foot and mouth disease in Cameroon. Preventive Veterinary Medicine. 155:1-10. https://doi.org/10.1016/j.prevetmed.2018.04.003.
Eschbaumer, M., Stenfeldt, C., Pacheco Tobin, J., Rekant, S.I., Arzt, J. 2016. Effect of storage conditions on subpopulations of peripheral blood T lymphocytes from naive cattle and cattle infected with foot-and-mouth disease virus. Veterinary Clinical Pathology. 45:110-115. https://doi.org/10.1111/vcp.12327.
Hayder, S.S., VanderWaal, K., Ranjan, R., Biswal, J.K., Subramaniam, S., Mohapatra, J.K., Sharma, G.K., Rout, M., Dash, B., Das, B., Prusty, B., Sharma, A.K., Stenfeldt, C., Perez, A., Rodriguez, L.L., Arzt, J. 2017. Foot-and-mouth disease virus transmission dynamics and persistence in a herd of vaccinated dairy cattle in India. Transboundary and Emerging Diseases. 65(2):e404-e415. https://doi.org/10.1111/tbed.12774.
