First isolation, in-vivo and genomic characterization of zoonotic variegated squirrel Bornavirus 1 (VSBV-1) isolates

Emerg Microbes Infect. 2020 Dec;9(1):2474-2484. doi: 10.1080/22221751.2020.1847604.

Abstract

The variegated squirrel bornavirus 1 (VSBV-1), a member of the family Bornaviridae, was discovered in 2015 in a series of lethal human infections. Screening approaches revealed kept exotic squirrels as the putative source of infection. Infectious virus was successfully isolated by co-cultivation of infected primary squirrel cells with permanent cell lines. For in vivo characterization, neonatal and adult Lewis rats were inoculated either intracranially, intranasally or subcutaneously. After 4.5 months, three out of fifteen neonatal intracranially inoculated rats were VSBV-1 genome positive in the central nervous system without showing clinical signs. Pathohistological examination revealed a non-purulent encephalitis. While infection of immune incompetent rats (neonatal) using the type species of mammalian bornaviruses, the Borna disease virus 1, proceed to an immune tolerant status, VSBV-1 infection could result in inflammation of neuronal tissue. Sequencing showed minor adaptations within the VSBV-1 genome comparing to the viral genomes from infected squirrels, cell cultures or rat tissues. In conclusion, we were able to generate the first VSBV-1 isolates and provide in vivo animal model data in Lewis rats revealing substantial differences between VSBV-1 and BoDV-1. Furthermore, the presented data are a precondition for insights into the transmission and pathogenesis of this novel zoonotic pathogen.

Keywords: Lewis rats; VSBV-1; Variegated squirrel bornavirus 1; animal trial; virus isolation.

MeSH terms

  • Adaptation, Physiological
  • Animals
  • Bornaviridae / genetics
  • Bornaviridae / isolation & purification
  • Bornaviridae / pathogenicity*
  • Cells, Cultured
  • Central Nervous System / virology
  • Chlorocebus aethiops
  • Coculture Techniques
  • Encephalitis, Viral / virology*
  • Female
  • Genome Size
  • Genome, Viral
  • Genotype
  • Male
  • Mononegavirales Infections / virology*
  • Primary Cell Culture
  • RNA, Viral / genetics*
  • Rats
  • Rats, Inbred Lew
  • Sciuridae / virology*
  • Sequence Analysis, RNA / methods*
  • Vero Cells

Substances

  • RNA, Viral

Grants and funding

Supported by grants from the Federal Ministry of Education and Research http://dx.doi.org/10.13039/501100002347: project ZooBoCo (Bundesministerium für Bildung und Forschung) (Zoonotic Bornavirus Consortium), within the research network for zoonotic infectious diseases, grant number 01KI1722A/01KI2005A and 01KI1722E/01KI2005E.