Squirrels as the Source of a New Viral Cause of Encephalitis
Three men, ages 62-72 years from the same region of Germany had onset of symptoms of encephalitis in late 2011. MRI revealed hyperintense cortical and basal ganglia lesions. Cerebrospinal fluid (CSF) white blood cell count ranged from 11-168 cells/μL with 79% lymphocytes (mostly atypical) in the only one with a cell differential. Lactate was elevated in each, the serum/CSF glucose ratios were normal, and protein was elevated. Their illness progressed over the next 2-4 months when it ended in their deaths at a time when extensive investigation had failed to identify an etiology. Of note is that during the course of their illness, all three developed deep venous thrombosis, and two suffered pulmonary embolism.
Epidemiological investigation found that all three men bred variegated squirrels and frequently met and exchanged breeding pairs. Pathogen-specific screening of a squirrel from the breeding population of one of the patients failed to detect an etiology, leading to metagenomic sequencing of a number of samples from the animal. This led to identification of sequence fragments with homologies to Mammalian 1 bornavirus, and targeted screening led to the detection of additional sequencing reads related to both mammalian and avian bornavirus. The investigators named the virus variegated squirrel 1 bornavirus (VSBV-1). Using derived primers, RT-PCR, VSBV-1 was detected in the squirrel and in samples from all three patients, including in brain tissue. Testing of samples from multiple controls, both with brain disease and healthy individuals, were all negative. Immunohistochemical staining of brain tissue from one of the patients was positive, and high antibody titers to the virus were present in CSF and serum of one patient tested.
COMMENTARY
This is yet another example of the power of modern science to detect new viral pathogens. The problem now has become the more difficult one of unequivocally demonstrating that the novel organisms are actually causal. In the cases described by Hoffman and colleagues, while Koch’s postulates have not been completely fulfilled, the evidence is overwhelming that this newly described bornavirus caused fatal encephalitis in these three individuals and that squirrels were the source of the virus.
Each of the individuals had intense exposure to the squirrels they were breeding, with each patient reporting having been scratched or bitten by them. Of note is that variegated squirrels are native to southern Mexico and Central America, so it is possible, if the virus has entered that population, that similar infections may be occurring in residents and visitors to those regions, assuming that the local squirrels are affected. Whether similar viruses are present in other squirrels is unknown.
Borna disease, originally known as “Hitzige Kopfkrankheit der Pferde” (“heated head disease of horses”) was first described in the 18th century and affects sheep, rabbits, and a variety of other animals in addition to horses. In addition, related avian bornaviruses cause disease in psittacines and have also been detected in other avians. Two decades ago, the possibility that bornavirus was associated with psychiatric disease in humans was examined and apparently rejected.
Evidence indicates that a newly discovered bornavirus caused infection in squirrels and was transmitted from them to three humans who developed encephalitis and died.
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