Pathogenesis and immunity of Avian bornavirus infections in birds
Final Report Abstract
During the first part of this project we generated recombinant modified vaccinia virus Ankara (MVA) and Newcastle disease virus (NDV) and Orf virus (ORFV) constructs, which are expressing the nucleoprotein (N) and phosphoprotein (P) of parrot bornavirus 4 (PaBV-4) and canary bornavirus 2 (CnBV-2). All vaccines were confirmed to be safe and elicit a bornavirus-specific immune response in cockatiels (Nymphicus hollandicus) and common canaries (Serinus canaria), the two most common avian bornavirus infection models. By heterologous prime-boost vaccination using combinations of NDV and MVA constructs, cockatiels were protected against subsequent challenge infection with a virulent field isolate and against bornavirus-related lesions and clinical disease. A comparison of recombinant MVA, NDV, ORFV vaccines demonstrated MVA to provide full protection against challenge infection, whereas neither NDV nor ORFV alone were sufficiently effective. The safety of the vaccines was further confirmed by vaccination of persistently PaBV-4-infected cockatiels. In these settings, vaccination with MVA and NDV constructs did not induce immunopathology, but also failed to contribute to viral clearance. This work provides an important step towards vaccination of birds, including endangered psittacine species, against avian bornavirus infections. In a second part of the project we established polymerase reconstitution (“minireplicon”) assays for several avian and mammalian bornaviruses, providing a crucial prerequisite for establishing reverse genetic systems for avian bornaviruses. Complete genomes of wildtype strains as well as recombinant viruses carrying reporter genes have been generated or are currently under construction. These newly established tools will be used to further investigate replication strategies of bornaviruses as well as for the identification of compounds with antiviral activity against bornaviruses. During this project, we already confirmed that avian bornavirus replication is inefficient in mammalian cells, suggesting an at best low zoonotic potential of this group of viruses. In addition, minireplicon assays showed that Ribavirin acts against PaBV-4 by inhibition of the viral polymerase.
Publications
- 2016, Phylogenetic analysis supports horizontal transmission as a driving force of the spread of avian bornaviruses. PloS one 11, e0160936
Rubbenstroth, D., Schmidt, V., Rinder, M., Legler, M., Twietmeyer, S., Schwemmer, P., Corman, V.M.
(See online at https://doi.org/10.1371/journal.pone.0160936) - 2016, Synergistic antiviral activity of ribavirin and interferon-alpha against parrot bornaviruses in avian cells. J Gen Virol 97, 2096-2103
Reuter, A., Horie, M., Höper, D., Ohnemus, A., Narr, A., Rinder, M., Beer, M., Staeheli, P., Rubbenstroth, D.
(See online at https://doi.org/10.1099/jgv.0.000555) - 2016, Viral vector vaccines expressing nucleoprotein and phosphoprotein genes of avian bornaviruses ameliorate homologous challenge infections in cockatiels and common canaries. Sci Rep 6, 36840
Olbert, M., Römer-Oberdörfer, A., Herden, C., Malberg, S., Runge, S., Staeheli, P., Rubbenstroth, D.
(See online at https://doi.org/10.1038/srep36840) - 2017, Viral vector vaccines protect cockatiels from inflammatory lesions after heterologous parrot bornavirus 2 challenge infection. Vaccine 35, 557-563
Runge, S., Olbert, M., Herden, C., Malberg, S., Römer-Oberdörfer, A., Staeheli, P., Rubbenstroth, D.
(See online at https://doi.org/10.1016/j.vaccine.2016.12.022)
