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Viruses 2018, 10(1), 33; https://doi.org/10.3390/v10010033

Causation of Acute Flaccid Paralysis by Myelitis and Myositis in Enterovirus-D68 Infected Mice Deficient in Interferon αβ/γ Receptor Deficient Mice

1
Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, 5600 Old Main Hill, Utah State University, Logan, UT 84322, USA
2
Utah Veterinary Diagnostics Laboratory, Department of Animal, Dairy, and Veterinary Sciences, 950 East 1400 North, Utah State University, Logan, UT 84341, USA
3
Department of Communication Disorders and Deaf Education, 2800 Old Main Hill, Utah State University, Logan, UT 84322, USA
*
Author to whom correspondence should be addressed.
Received: 18 December 2017 / Revised: 4 January 2018 / Accepted: 8 January 2018 / Published: 12 January 2018
(This article belongs to the Section Animal Viruses)
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Abstract

Enterovirus D68 (EV-D68) caused a large outbreak in the summer and fall of 2014 in the United States. It causes serious respiratory disease, but causation of associated paralysis is controversial, because the virus is not routinely identified in cerebrospinal fluid. To establish clinical correlates with human disease, we evaluated EV-D68 infection in non-lethal paralysis mouse models. Ten-day-old mice lacking interferon responses were injected intraperitoneally with the virus. Paralysis developed in hindlimbs. After six weeks of paralysis, the motor neurons were depleted due to viral infection. Hindlimb muscles were also infected and degenerating. Even at the earliest stage of paralysis, muscles were still infected and were degenerating, in addition to presence of virus in the spinal cord. To model natural respiratory infection, five-day-old mice were infected intranasally with EV-D68. Two of the four infected mice developed forelimb paralysis. The affected limbs had muscle disease, but no spinal cord infection was detected. The unique contributions of this study are that EV-D68 causes paralysis in mice, and that causation by muscle disease, with or without spinal cord disease, may help to resolve the controversy that the virus can cause paralysis, even if it cannot be identified in cerebrospinal fluid. View Full-Text
Keywords: enterovirus; enterovirus-D68; paralysis; myelitis; myositis; electrophysiology; spinal cord; motor neurons; muscle atrophy enterovirus; enterovirus-D68; paralysis; myelitis; myositis; electrophysiology; spinal cord; motor neurons; muscle atrophy
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Morrey, J.D.; Wang, H.; Hurst, B.L.; Zukor, K.; Siddharthan, V.; Van Wettere, A.J.; Sinex, D.G.; Tarbet, E.B. Causation of Acute Flaccid Paralysis by Myelitis and Myositis in Enterovirus-D68 Infected Mice Deficient in Interferon αβ/γ Receptor Deficient Mice. Viruses 2018, 10, 33.

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