Development of Variegated squirrel bornavirus -1 (VSBV-1) animal models: the tenacious search for the appropriate species

Variegated squirrel bornavirus 1 (VSBV-1) is a zoonotic virus and it is assumed that exotic squirrels represent reservoir hosts. The closest relative, classical Borna disease virus 1 (BoDV-1), is known since a long time and causes fatal Borna disease in horses and sheep in Europe. Today we know that both mammalian bornaviruses can cause severe encephalitis in humans. The aim of this study was to test the susceptibility of different rodent models and non-human primates for VSBV-1, to characterize the course of disease and thereby to establish an infection model which could provide deeper insights into transmissions pathways, pathogenesis and countermeasure development. VSBV-1 infection studies were done with different rodents (rats, bank voles, mice, gerbils and guinea pigs) in addition to rhesus macaques. Rodents of different ages were infected with VSBV-1 by different infection routes (intracerebral, intranasal or subcutaneous). Rhesus macaques were inoculated either by the intracerebral route or by multiple routes (intranasal, conjunctival, intramuscular and subcutaneously; reflecting possible natural infection routes). All animals were monitored for signs of disease and virus shedding. So far, none of the tested rodents fulfilled all criteria to be used as an infection model for VSBV-1 without virus adaptation whereas macaques intracerebrally infected with mammalian bornaviruses develop a human-like disease and may serve as a surrogate model for human bornavirus infection.