Metagenomics-enabled reverse-genetics assembly and characterization of myotis bat morbillivirus

Satoshi Ikegame, Jillian C. Carmichael, Heather Wells, Robert L. Furler O’Brien, Joshua A. Acklin, Hsin Ping Chiu, Kasopefoluwa Y. Oguntuyo, Robert M. Cox, Aum R. Patel, Shreyas Kowdle, Christian S. Stevens, Miles Eckley, Shijun Zhan, Jean K. Lim, Ethan C. Veit, Matthew J. Evans, Takao Hashiguchi, Edison Durigon, Tony Schountz, Jonathan H. EpsteinRichard K. Plemper, Peter Daszak, Simon J. Anthony, Benhur Lee

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Morbilliviruses are among the most contagious viral pathogens of mammals. Although previous metagenomic surveys have identified morbillivirus sequences in bats, full-length morbilliviruses from bats are limited. Here we characterize the myotis bat morbillivirus (MBaMV) from a bat surveillance programme in Brazil, whose full genome was recently published. We demonstrate that the fusion and receptor binding protein of MBaMV utilize bat CD150 and not human CD150, as an entry receptor in a mammalian cell line. Using reverse genetics, we produced a clone of MBaMV that infected Vero cells expressing bat CD150. Electron microscopy of MBaMV-infected cells revealed budding of pleomorphic virions, a characteristic morbillivirus feature. MBaMV replication reached 103–105 plaque-forming units ml−1 in human epithelial cell lines and was dependent on nectin-4. Infection of human macrophages also occurred, albeit 2–10-fold less efficiently than measles virus. Importantly, MBaMV is restricted by cross-neutralizing human sera elicited by measles, mumps and rubella vaccination and is inhibited by orally bioavailable polymerase inhibitors in vitro. MBaMV-encoded P/V genes did not antagonize human interferon induction. Finally, we show that MBaMV does not cause disease in Jamaican fruit bats. We conclude that, while zoonotic spillover into humans may theoretically be plausible, MBaMV replication would probably be controlled by the human immune system.

Original languageEnglish
Pages (from-to)1108-1122
Number of pages15
JournalNature Microbiology
Volume8
Issue number6
DOIs
StatePublished - Jun 2023

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