Journal
ANTIVIRAL RESEARCH
Volume 110, Issue -, Pages 132-141Publisher
ELSEVIER
DOI: 10.1016/j.antiviral.2014.07.013
Keywords
Rabies virus; MCP-1; BBB (blood-brain barrier); VNA (virus-neutralizing antibody); Occludin; Claudin-5
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Funding
- Public Health Service from the National Institute of Allergy and Infectious Diseases [AI-051560, AI-093369]
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Rabies virus (RABV) is a neurotropic virus that causes fatal disease in humans and animals. Currently there is no cure for rabies once clinical signs appear. It is believed that once RABV enters the central nervous system (CNS), virus neutralizing antibodies (VNAs) in the periphery cannot pass through the blood-brain barrier (BBB) and into the CNS. Furthermore, it has been hypothesized that VNAs produced in the CNS by invading B cells, rather than those produced in the periphery and then transported into the CNS, are important in clearing RABV from the CNS. In the present study, mouse serum containing VNA was administered intravenously into mice after infection with wild-type RABV. Our studies demonstrate that exogenous administration of VNAs is crucial in the clearance of RABV from the brain and prevent the development of rabies in both immunocompetent and immunocompromised mice as long as the BBB permeability remains enhanced. This present study therefore provides a foundation for the possibility of developing VNA therapy for clinical rabies in humans. (C) 2014 Elsevier B.V. All rights reserved.
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