Entry, Replication, Immune Evasion, and Neurotoxicity of Synthetically Engineered Bat-Borne Mumps Virus
Nadine Krüger,
Christian Sauder,
Sarah Hüttl,
Jan Papies,
Kathleen Voigt,
Georg Herrler,
Kornelia Hardes,
Torsten Steinmetzer,
Claes Örvell,
Jan Felix Drexler,
Christian Drosten,
Steven Rubin,
Marcel Alexander Müller,
Markus Hoffmann
Affiliations
Nadine Krüger
Institute of Virology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany; Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, 30559 Hannover, Germany; Corresponding author
Christian Sauder
Food and Drug Administration (FDA), Center for Biologics Evaluation and Research (CBER), Silver Spring, MD 20993, USA
Sarah Hüttl
Institute of Virology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany; Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, 30559 Hannover, Germany
Jan Papies
Institute of Virology, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 10117 Berlin, Germany
Kathleen Voigt
Institute of Virology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany; Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, 30559 Hannover, Germany
Georg Herrler
Institute of Virology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany
Kornelia Hardes
Institute of Pharmaceutical Chemistry, Philipps-University Marburg, 35032 Marburg, Germany
Torsten Steinmetzer
Institute of Pharmaceutical Chemistry, Philipps-University Marburg, 35032 Marburg, Germany
Claes Örvell
Division of Laboratory Medicine, Karolinska Institutet, 17177 Stockholm, Sweden
Jan Felix Drexler
Institute of Virology, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 10117 Berlin, Germany
Christian Drosten
Institute of Virology, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 10117 Berlin, Germany
Steven Rubin
Food and Drug Administration (FDA), Center for Biologics Evaluation and Research (CBER), Silver Spring, MD 20993, USA
Marcel Alexander Müller
Institute of Virology, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 10117 Berlin, Germany
Markus Hoffmann
Infection Biology Unit, German Primate Center, 37077 Göttingen, Germany
Summary: Bats harbor a plethora of viruses with an unknown zoonotic potential. In-depth functional characterization of such viruses is often hampered by a lack of virus isolates. The genome of a virus closely related to human mumps viruses (hMuV) was detected in African fruit bats, batMuV. Efforts to characterize batMuV were based on directed expression of the batMuV glycoproteins or use of recombinant chimeric hMuVs harboring batMuV glycoprotein. Although these studies provided initial insights into the functionality of batMuV glycoproteins, the host range, replication competence, immunomodulatory functions, virulence, and zoonotic potential of batMuV remained elusive. Here, we report the successful rescue of recombinant batMuV. BatMuV infects human cells, is largely resistant to the host interferon response, blocks interferon induction and TNF-α activation, and is neurotoxic in rats. Anti-hMuV antibodies efficiently neutralize batMuV. The striking similarities between hMuV and batMuV point at the putative zoonotic potential of batMuV. : Humans were considered the only natural host of mumps viruses until the discovery of a closely related virus in bats. By reconstitution of the bat mumps virus, Krüger et al. show that the virus efficiently replicates in bat and in human cells, can evade innate immune responses in both hosts, and possesses neurotoxic properties. Keywords: mumps virus, bat-derived viruses, zoonosis, reverse genetics, viral entry, immune evasion
