RTP4 Is a Potent IFN-Inducible Anti-flavivirus Effector Engaged in a Host-Virus Arms Race in Bats and Other Mammals

Ian N. Boys, Elaine Xu, Katrina B. Mar, Pamela C. De La Cruz-Rivera, Jennifer L. Eitson, Benjamin Moon, John W. Schoggins

Research output: Contribution to journalArticlepeer-review

Abstract

Among mammals, bats are particularly rich in zoonotic viruses, including flaviviruses. Certain bat species can be productively yet asymptomatically infected with viruses that cause overt disease in other species. However, little is known about the antiviral effector repertoire in bats relative to other mammals. Here, we report the black flying fox receptor transporter protein 4 (RTP4) as a potent interferon (IFN)-inducible inhibitor of human pathogens in the Flaviviridae family, including Zika, West Nile, and hepatitis C viruses. Mechanistically, RTP4 associates with the flavivirus replicase, binds viral RNA, and suppresses viral genome amplification. Comparative approaches revealed that RTP4 undergoes positive selection, that a flavivirus can mutate to escape RTP4-imposed restriction, and that diverse mammalian RTP4 orthologs exhibit striking patterns of specificity against distinct Flaviviridae members. Our findings reveal an antiviral mechanism that has likely adapted over 100 million years of mammalian evolution to accommodate unique host-virus genetic conflicts.

Original languageEnglish (US)
Pages (from-to)712-723.e9
JournalCell Host and Microbe
Volume28
Issue number5
DOIs
StatePublished - Nov 11 2020

Keywords

  • antiviral immunity
  • bats
  • evolution
  • flavivirus
  • genetic arms race
  • interferon
  • restriction factor
  • virus-host interactions

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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