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Journal of Virology, August 2007, p. 7993-7998, Vol. 81, No. 15
0022-538X/07/$08.00+0     doi:10.1128/JVI.00710-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Lethal Silver-Haired Bat Rabies Virus Infection Can Be Prevented by Opening the Blood-Brain Barrier{triangledown}

Anirban Roy and D. Craig Hooper*

Center for Neurovirology, Kimmel Cancer Center, Thomas Jefferson University, 1020 Locust Street, Philadelphia, Pennsylvania 19107

Received 3 April 2007/ Accepted 11 May 2007

Silver-haired bat rabies virus (SHBRV) infection induces a strong virus-specific immune response in the periphery of the host, but death is common due to the failure to open the blood-brain barrier (BBB) and deliver immune effectors to central nervous system (CNS) tissues. Mice with an SJL background are less susceptible to lethal infection with rabies viruses. In addition, these animals are known to have reduced hypothalamus-pituitary-adrenal (HPA) axis activity and an elevated capacity to mediate CNS inflammatory responses. We show here that approximately one-half of PLSJL mice survive an SHBRV infection that is invariably lethal for 129/SvEv mice. This difference is associated with the elevated capacity of PLSJL mice to mediate BBB permeability changes in response to the infection. The induction of more extensive BBB permeability and CNS inflammation in these animals results in greater virus clearance and improved survival. On the other hand, treatment of SHBRV-infected PLSJL mice with the steroid hormone dehydroepiandrosterone reduced BBB permeability changes and caused greater mortality. We conclude that the infiltration of immune effectors across the BBB is critical to surviving a rabies virus infection and that HPA axis activity may influence this process.

* Corresponding author. Mailing address: Center for Neurovirology, Thomas Jefferson University, 1020 Locust St., JAH 454, Philadelphia, PA 19107-6799. Phone: (215) 503-1774. Fax: (215) 923-7745. E-mail: douglas.hooper{at}jefferson.edu

{triangledown} Published ahead of print on 16 May 2007.

Journal of Virology, August 2007, p. 7993-7998, Vol. 81, No. 15
0022-538X/07/$08.00+0     doi:10.1128/JVI.00710-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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