Reston virus causes severe respiratory disease in young domestic pigs
- aLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840;
- bRocky Mountain Veterinary Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840;
- cCenter for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032;
- dResearch Technologies Branch, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840;
- eDepartment of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66502;
- fCenter of Excellence for Emerging and Zoonotic Animal Diseases, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66502
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Edited by Peter Palese, Icahn School of Medicine at Mount Sinai, New York, NY, and approved November 23, 2020 (received for review July 24, 2020)

Significance
The emergence of Reston virus (RESTV) in domestic pigs in the Philippines and, subsequently, the detection of RESTV sequences in pigs in China are serious human and animal health concerns. Food safety is an immediate fear, and pathogenicity and potential for zoonotic transmission are important concerns. To find answers for those problems, we performed a pathogenicity study in young domestic pigs. We could demonstrate that young pigs develop severe respiratory disease upon RESTV infection and shed virus from mucosal membranes of the respiratory tract. We conclude that RESTV should be considered a livestock pathogen with zoonotic transmission impacting on animal and perhaps even human health.
Abstract
Reston virus (RESTV), an ebolavirus, causes clinical disease in macaques but has yet only been associated with rare asymptomatic infections in humans. Its 2008 emergence in pigs in the Philippines raised concerns about food safety, pathogenicity, and zoonotic potential, questions that are still unanswered. Until today, the virulence of RESTV for pigs has remained elusive, with unclear pathogenicity in naturally infected animals and only one experimental study demonstrating susceptibility and evidence for shedding but no disease. Here we show that combined oropharyngeal and nasal infection of young (3- to 7-wk-old) Yorkshire cross pigs with RESTV resulted in severe respiratory disease, with most animals reaching humane endpoint within a week. RESTV-infected pigs developed severe cyanosis, tachypnea, and acute interstitial pneumonia, with RESTV shedding from oronasal mucosal membranes. Our studies indicate that RESTV should be considered a livestock pathogen with zoonotic potential.
Footnotes
- ↵1To whom correspondence may be addressed. Email: feldmannh{at}niaid.nih.gov.
Author contributions: J.A.R., E.d.W., and H.F. designed research; E.H., G.S., F.F., P.W.H., A.O., J.L., D.L., T.T., D.P.S., M.P., and H.F. performed research; F.F., P.W.H., J.L., D.L., T.T., D.P.S., and M.P. contributed new reagents/analytic tools; E.H., G.S., F.F., P.W.H., A.O., J.L., D.L., T.T., D.P.S., M.P., J.A.R., E.d.W., and H.F. analyzed data; and E.H., G.S., F.F., P.W.H., A.O., J.L., D.P.S., J.A.R., E.d.W., and H.F. wrote the paper.
The authors declare no competing interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2015657118/-/DCSupplemental.
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