Authors

Clement W Gnanadurai, Department of Pathology, College of Veterinary Medicine, University of Georgia
Ming Zhou, Department of Pathology, College of Veterinary Medicine, University of Georgia
Wenqi He, Department of Pathology, College of Veterinary Medicine, University of Georgia
Christina M Leyson, Department of Pathology, College of Veterinary Medicine, University of Georgia
Chien-Tsun Huang, Department of Pathology, College of Veterinary Medicine, University of Georgia
Gregory Salyards, Department of Pathology, College of Veterinary Medicine, University of Georgia; Department of Population Health, College of Veterinary Medicine, University of Georgia,
Stephen B Harvey, Department of Population Health, College of Veterinary Medicine, University of Georgia,
Zhenhai Chen, Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia
Biao He, Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia
Yang Yang, Department of Pathology, College of Veterinary Medicine, University of Georgia; State-key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University
D C Hooper, Departments of Cancer Biology and Neurological Surgery, Thomas Jefferson UniversityFollow
Berhnard Dietzchold, Departments of Cancer Biology and Neurological Surgery, Thomas Jefferson University
Zhen F Fu, Department of Pathology, College of Veterinary Medicine, University of Georgia; State-key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University

Document Type

Article

Publication Date

9-1-2013

Comments

This article has been peer reviewed. It was published in: PLoS neglected tropical diseases.

Volume 7, Issue 9, September 2013, Article number e2375.

The published version is available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777866/. DOI: 10.1371/journal.pntd.0002375

Copyright © 2013 Gnanadurai et al.

Abstract

BACKGROUND: Rabies is traditionally considered a uniformly fatal disease after onset of clinical manifestations. However, increasing evidence indicates that non-lethal infection as well as recovery from flaccid paralysis and encephalitis occurs in laboratory animals as well as humans.

METHODOLOGY/PRINCIPAL FINDINGS: Non-lethal rabies infection in dogs experimentally infected with wild type dog rabies virus (RABV, wt DRV-Mexico) correlates with the presence of high level of virus neutralizing antibodies (VNA) in the cerebral spinal fluid (CSF) and mild immune cell accumulation in the central nervous system (CNS). By contrast, dogs that succumbed to rabies showed only little or no VNA in the serum or in the CSF and severe inflammation in the CNS. Dogs vaccinated with a rabies vaccine showed no clinical signs of rabies and survived challenge with a lethal dose of wild-type DRV. VNA was detected in the serum, but not in the CSF of immunized dogs. Thus the presence of VNA is critical for inhibiting virus spread within the CNS and eventually clearing the virus from the CNS.

CONCLUSIONS/SIGNIFICANCE: Non-lethal infection with wt RABV correlates with the presence of VNA in the CNS. Therefore production of VNA within the CNS or invasion of VNA from the periphery into the CNS via compromised blood-brain barrier is important for clearing the virus infection from CNS, thereby preventing an otherwise lethal rabies virus infection.

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