@article{97ad23bfaaa544999d4b30c3b498ab73,
title = "RTP4 Is a Potent IFN-Inducible Anti-flavivirus Effector Engaged in a Host-Virus Arms Race in Bats and Other Mammals",
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.",
keywords = "antiviral immunity, bats, evolution, flavivirus, genetic arms race, interferon, restriction factor, virus-host interactions",
author = "Boys, {Ian N.} and Elaine Xu and Mar, {Katrina B.} and {De La Cruz-Rivera}, {Pamela C.} and Eitson, {Jennifer L.} and Benjamin Moon and Schoggins, {John W.}",
note = "Funding Information: We thank Lin-Fa Wang for providing PaKi cells; Susan J. Wong for providing WNV NS3 and NS5 antibodies; Nicholas Conrad, Dustin Hancks, and Maikke Ohlson for critical manuscript feedback; and Julio Ruiz, Anna Scarborough, and Nicholas Conrad for helpful discussions. We acknowledge the UT Southwestern (UTSW) Bioinformatics Lab for their assistance. This study was in part supported by grants to J.W.S. ( NIH AI117922 , UTSW High Impact / High Risk Grant Program , UTSW Endowed Scholars Program , the Rita Allen Foundation , The Welch Foundation [ I-2013-20190330 ], and an Investigators in the pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund ). I.N.B. was supported by the NSF GRFP (grant no. 2016217834 ) and NIH T32 training grant AI005284 . K.B.M. was supported by the NIH T32 training grant AI005284 . E.X. was supported by the Amgen Foundation through the Amgen Scholars program . Any opinion, findings, and conclusions or recommendations expressed in this material are those of the authors(s) and do not necessarily reflect the views of funding agencies. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = nov,
day = "11",
doi = "10.1016/j.chom.2020.09.014",
language = "English (US)",
volume = "28",
pages = "712--723.e9",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "5",
}