Cellular RNA-binding proteins (RBPs) are pivotal for the viral lifecycle, mediating key host-virus interactions that promote or repress virus infection. While these interactions have been largely studied in the vertebrate host, no comprehensive analyses of protein-RNA interactions occurring in cells of arbovirus vectors, in particular ticks, have been performed to date. Here we systematically identified the responses of the RNA-binding proteome (RBPome) to infection with a prototype bunyavirus (Uukuniemi virus; UUKV) in tick cells and discovered changes in RNA-binding activity for 283 proteins. In an orthogonal approach, we analysed the composition of the viral ribonucleoprotein by immunoprecipitation of UUKV nucleocapsid protein (N) in infected cells. We found many tick RBPs that are regulated by UUKV infection and associate with viral nucleocapsid protein complexes, and we confirmed experimentally that they impact UUKV infection. This includes the tick homolog of topoisomerase 3B (TOP3B), a protein able to manipulate the topology of RNA, which particularly affected viral particle production. Our data thus reveals the first protein-RNA interaction map for infected tick cells.

Department of Biochemistry University of Oxford Oxford United Kingdom

Department of Chemistry University of Oxford Oxford United Kingdom

Department of Experimental Biology Faculty of Science Masaryk University Brno Czech Republic

Department of Infection Biology and Microbiomes Institute of Infection Veterinary and Ecological Sciences University of Liverpool Liverpool United Kingdom

Departments of Tropical Disease Biology and Vector Biology Liverpool School of Tropical Medicine Liverpool United Kingdom

FingerPrints Proteomics Facility School of Life Sciences University of Dundee Dundee Scotland United Kingdom

Medical Research Council University of Glasgow Centre for Virus Research Glasgow Scotland United Kingdom

Rosalind Franklin Institute Harwell Science and Innovation Campus Oxford Oxfordshire United Kingdom

Zobrazit více v PubMed

Oker-Blom N, Salminen A, Brummer-Korvenkontio M, Kaeaeriaeinen L, Weckstroem P. Isolation of some viruses other than typical tick-borne encephalitis viruses from ixodes ricinus ticks In Finland. Ann Med Exp Biol Fenn. 1964;42:109–12. PubMed

Mazelier M, Rouxel RN, Zumstein M, Mancini R, Bell-Sakyi L, Lozach P-Y. Uukuniemi Virus as a Tick-Borne Virus Model. J Virol. 2016;90(15):6784–98. doi: 10.1128/JVI.00095-16 PubMed DOI PMC

Rezelj VV, Överby AK, Elliott RM. Generation of mutant Uukuniemi viruses lacking the nonstructural protein NSs by reverse genetics indicates that NSs is a weak interferon antagonist. J Virol. 2015;89(9):4849–56. doi: 10.1128/JVI.03511-14 PubMed DOI PMC

Pettersson RF, Hewlett MJ, Baltimore D, Coffin JM. The genome of Uukuniemi virus consists of three unique RNA segments. Cell. 1977;11(1):51–63. doi: 10.1016/0092-8674(77)90316-6 PubMed DOI

Ranki M, Pettersson RF. Uukuniemi virus contains an RNA polymerase. J Virol. 1975;16(6):1420–5. doi: 10.1128/JVI.16.6.1420-1425.1975 PubMed DOI PMC

Overby AK, Pettersson RF, Grünewald K, Huiskonen JT. Insights into bunyavirus architecture from electron cryotomography of Uukuniemi virus. Proc Natl Acad Sci U S A. 2008;105(7):2375–9. doi: 10.1073/pnas.0708738105 PubMed DOI PMC

Lozach P-Y, Kühbacher A, Meier R, Mancini R, Bitto D, Bouloy M, et al. DC-SIGN as a receptor for phleboviruses. Cell Host Microbe. 2011;10(1):75–88. doi: 10.1016/j.chom.2011.06.007 PubMed DOI

Lozach P-Y, Mancini R, Bitto D, Meier R, Oestereich L, Overby AK, et al. Entry of bunyaviruses into mammalian cells. Cell Host Microbe. 2010;7(6):488–99. doi: 10.1016/j.chom.2010.05.007 PubMed DOI PMC

Meier R, Franceschini A, Horvath P, Tetard M, Mancini R, von Mering C, et al. Genome-wide small interfering RNA screens reveal VAMP3 as a novel host factor required for Uukuniemi virus late penetration. J Virol. 2014;88(15):8565–78. doi: 10.1128/JVI.00388-14 PubMed DOI PMC

Elliott RM, Brennan B. Emerging phleboviruses. Curr Opin Virol. 2014;5(100):50–7. doi: 10.1016/j.coviro.2014.01.011 PubMed DOI PMC

Malet H, Williams HM, Cusack S, Rosenthal M. The mechanism of genome replication and transcription in bunyaviruses. PLoS Pathog. 2023;19(1):e1011060. doi: 10.1371/journal.ppat.1011060 PubMed DOI PMC

Eifan SA, Elliott RM. Mutational analysis of the Bunyamwera orthobunyavirus nucleocapsid protein gene. J Virol. 2009;83(21):11307–17. doi: 10.1128/JVI.01460-09 PubMed DOI PMC

Mottram TJ, Li P, Dietrich I, Shi X, Brennan B, Varjak M, et al. Mutational analysis of Rift Valley fever phlebovirus nucleocapsid protein indicates novel conserved, functional amino acids. PLoS Negl Trop Dis. 2017;11(12):e0006155. doi: 10.1371/journal.pntd.0006155 PubMed DOI PMC

Rezelj VV, Li P, Chaudhary V, Elliott RM, Jin D-Y, Brennan B. Differential Antagonism of Human Innate Immune Responses by Tick-Borne Phlebovirus Nonstructural Proteins. mSphere. 2017;2(3):e00234-17. doi: 10.1128/mSphere.00234-17 PubMed DOI PMC

Palacios G, Savji N, Travassos da Rosa A, Guzman H, Yu X, Desai A, et al. Characterization of the Uukuniemi virus group (Phlebovirus: Bunyaviridae): evidence for seven distinct species. J Virol. 2013;87(6):3187–95. doi: 10.1128/JVI.02719-12 PubMed DOI PMC

Salata C, Moutailler S, Attoui H, Zweygarth E, Decker L, Bell-Sakyi L. How relevant are in vitro culture models for study of tick-pathogen interactions? Pathog Glob Health. 2021;115(7–8):437–55. doi: 10.1080/20477724.2021.1944539 PubMed DOI PMC

Miller JR, Koren S, Dilley KA, Harkins DM, Stockwell TB, Shabman RS, et al. A draft genome sequence for the Ixodes scapularis cell line, ISE6. F1000Res. 2018;7:297. doi: 10.12688/f1000research.13635.1 PubMed DOI PMC

Jia N, Wang J, Shi W, Du L, Sun Y, Zhan W, et al. Large-Scale Comparative Analyses of Tick Genomes Elucidate Their Genetic Diversity and Vector Capacities. Cell. 2020;182(5):1328-1340.e13. doi: 10.1016/j.cell.2020.07.023 PubMed DOI

Gulia-Nuss M, Nuss AB, Meyer JM, Sonenshine DE, Roe RM, Waterhouse RM, et al. Genomic insights into the Ixodes scapularis tick vector of Lyme disease. Nat Commun. 2016;7:10507. doi: 10.1038/ncomms10507 PubMed DOI PMC

Bell-Sakyi L, Zweygarth E, Blouin EF, Gould EA, Jongejan F. Tick cell lines: tools for tick and tick-borne disease research. Trends Parasitol. 2007;23(9):450–7. doi: 10.1016/j.pt.2007.07.009 PubMed DOI

Schnettler E, Tykalová H, Watson M, Sharma M, Sterken MG, Obbard DJ, et al. Induction and suppression of tick cell antiviral RNAi responses by tick-borne flaviviruses. Nucleic Acids Res. 2014;42(14):9436–46. doi: 10.1093/nar/gku657 PubMed DOI PMC

Weisheit S, Villar M, Tykalová H, Popara M, Loecherbach J, Watson M, et al. Ixodes scapularis and Ixodes ricinus tick cell lines respond to infection with tick-borne encephalitis virus: transcriptomic and proteomic analysis. Parasit Vectors. 2015;8:599. doi: 10.1186/s13071-015-1210-x PubMed DOI PMC

Grabowski JM, Gulia-Nuss M, Kuhn RJ, Hill CA. RNAi reveals proteins for metabolism and protein processing associated with Langat virus infection in Ixodes scapularis (black-legged tick) ISE6 cells. Parasit Vectors. 2017;10(1):24. doi: 10.1186/s13071-016-1944-0 PubMed DOI PMC

McNally KL, Mitzel DN, Anderson JM, Ribeiro JMC, Valenzuela JG, Myers TG, et al. Differential salivary gland transcript expression profile in Ixodes scapularis nymphs upon feeding or flavivirus infection. Ticks Tick Borne Dis. 2012;3(1):18–26. doi: 10.1016/j.ttbdis.2011.09.003 PubMed DOI PMC

Mansfield KL, Cook C, Ellis RJ, Bell-Sakyi L, Johnson N, Alberdi P, et al. Tick-borne pathogens induce differential expression of genes promoting cell survival and host resistance in Ixodes ricinus cells. Parasit Vectors. 2017;10(1):81. doi: 10.1186/s13071-017-2011-1 PubMed DOI PMC

Simser JA, Macaluso KR, Mulenga A, Azad AF. Immune-responsive lysozymes from hemocytes of the American dog tick, Dermacentor variabilis and an embryonic cell line of the Rocky Mountain wood tick, D. andersoni. Insect Biochem Mol Biol. 2004;34(12):1235–46. doi: 10.1016/j.ibmb.2004.07.003 PubMed DOI

Sidak-Loftis LC, Rosche KL, Pence N, Ujczo JK, Hurtado J, Fisk EA, et al. The Unfolded-Protein Response Triggers the Arthropod Immune Deficiency Pathway. mBio. 2022;13(4):e0070322. doi: 10.1128/mbio.00703-22 PubMed DOI PMC

Uckeley ZM, Moeller R, Kühn LI, Nilsson E, Robens C, Lasswitz L, et al. Quantitative Proteomics of Uukuniemi Virus-host Cell Interactions Reveals GBF1 as Proviral Host Factor for Phleboviruses. Mol Cell Proteomics. 2019;18(12):2401–17. doi: 10.1074/mcp.RA119.001631 PubMed DOI PMC

Castello A, Iselin L. Viral RNA Is a Hub for Critical Host-Virus Interactions. Subcell Biochem. 2023;106:365–85. doi: 10.1007/978-3-031-40086-5_13 PubMed DOI

Bermudez Y, Hatfield D, Muller M. A Balancing Act: The Viral-Host Battle over RNA Binding Proteins. Viruses. 2024;16(3):474. doi: 10.3390/v16030474 PubMed DOI PMC

Garcia-Moreno M, Noerenberg M, Ni S, Järvelin AI, González-Almela E, Lenz CE, et al. System-wide Profiling of RNA-Binding Proteins Uncovers Key Regulators of Virus Infection. Mol Cell. 2019;74(1):196-211.e11. doi: 10.1016/j.molcel.2019.01.017 PubMed DOI PMC

Kamel W, Noerenberg M, Cerikan B, Chen H, Järvelin AI, Kammoun M, et al. Global analysis of protein-RNA interactions in SARS-CoV-2-infected cells reveals key regulators of infection. Mol Cell. 2021;81(13):2851-2867.e7. doi: 10.1016/j.molcel.2021.05.023 PubMed DOI PMC

Lisy S, Rothamel K, Ascano M. RNA Binding Proteins as Pioneer Determinants of Infection: Protective, Proviral, or Both? Viruses. 2021;13(11):2172. doi: 10.3390/v13112172 PubMed DOI PMC

Castello A, Horos R, Strein C, Fischer B, Eichelbaum K, Steinmetz LM, et al. System-wide identification of RNA-binding proteins by interactome capture. Nat Protoc. 2013;8(3):491–500. doi: 10.1038/nprot.2013.020 PubMed DOI

Kurtti TJ, Munderloh UG, Andreadis TG, Magnarelli LA, Mather TN. Tick cell culture isolation of an intracellular prokaryote from the tick Ixodes scapularis. J Invertebr Pathol. 1996;67(3):318–21. doi: 10.1006/jipa.1996.0050 PubMed DOI

Iselin L, Palmalux N, Kamel W, Simmonds P, Mohammed S, Castello A. Uncovering viral RNA-host cell interactions on a proteome-wide scale. Trends Biochem Sci. 2022;47(1):23–38. doi: 10.1016/j.tibs.2021.08.002 PubMed DOI PMC

Perez-Perri JI, Noerenberg M, Kamel W, Lenz CE, Mohammed S, Hentze MW, et al. Global analysis of RNA-binding protein dynamics by comparative and enhanced RNA interactome capture. Nat Protoc. 2021;16(1):27–60. doi: 10.1038/s41596-020-00404-1 PubMed DOI PMC

Olschewski S, Cusack S, Rosenthal M. The Cap-Snatching Mechanism of Bunyaviruses. Trends Microbiol. 2020;28(4):293–303. doi: 10.1016/j.tim.2019.12.006 PubMed DOI

Ruscica V, Iselin L, Hull R, Embarc-Buh A, Narayanan S. XRN1 supplies free nucleotides to feed alphavirus replication. bioRxiv. 2024.

Blakqori G, van Knippenberg I, Elliott RM. Bunyamwera orthobunyavirus S-segment untranslated regions mediate poly(A) tail-independent translation. J Virol. 2009;83(8):3637–46. doi: 10.1128/JVI.02201-08 PubMed DOI PMC

Bouloy M, Pardigon N, Vialat P, Gerbaud S, Girard M. Characterization of the 5’ and 3’ ends of viral messenger RNAs isolated from BHK21 cells infected with Germiston virus (Bunyavirus). Virology. 1990;175(1):50–8. doi: 10.1016/0042-6822(90)90185-t PubMed DOI

Castello A, Fischer B, Eichelbaum K, Horos R, Beckmann BM, Strein C, et al. Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell. 2012;149(6):1393–406. doi: 10.1016/j.cell.2012.04.031 PubMed DOI

Sysoev VO, Fischer B, Frese CK, Gupta I, Krijgsveld J, Hentze MW, et al. Global changes of the RNA-bound proteome during the maternal-to-zygotic transition in Drosophila. Nat Commun. 2016;7:12128. doi: 10.1038/ncomms12128 PubMed DOI PMC

Wessels H-H, Imami K, Baltz AG, Kolinski M, Beldovskaya A, Selbach M, et al. The mRNA-bound proteome of the early fly embryo. Genome Res. 2016;26(7):1000–9. doi: 10.1101/gr.200386.115 PubMed DOI PMC

Schuster S, Miesen P, van Rij RP. Antiviral RNAi in Insects and Mammals: Parallels and Differences. Viruses. 2019;11(5):448. doi: 10.3390/v11050448 PubMed DOI PMC

Berkhout B, Haasnoot J. The interplay between virus infection and the cellular RNA interference machinery. FEBS Lett. 2006;580(12):2896–902. doi: 10.1016/j.febslet.2006.02.070 PubMed DOI PMC

Hornak KE, Lanchy J-M, Lodmell JS. RNA Encapsidation and Packaging in the Phleboviruses. Viruses. 2016;8(7):194. doi: 10.3390/v8070194 PubMed DOI PMC

Petit MJ, Flory C, Gu Q, Fares M, Lamont D, Score A, et al. Multi-omics analysis of SFTS virus infection in Rhipicephalus microplus cells reveals antiviral tick factors. Nat Commun. 2025;16(1):4732. doi: 10.1038/s41467-025-59565-w PubMed DOI PMC

Scherer C, Knowles J, Sreenu VB, Fredericks AC, Fuss J, Maringer K, et al. An Aedes aegypti-Derived Ago2 Knockout Cell Line to Investigate Arbovirus Infections. Viruses. 2021;13(6):1066. doi: 10.3390/v13061066 PubMed DOI PMC

Xu Y, Zhong Z, Ren Y, Ma L, Ye Z, Gao C, et al. Antiviral RNA interference in disease vector (Asian longhorned) ticks. PLoS Pathog. 2021;17(12):e1010119. doi: 10.1371/journal.ppat.1010119 PubMed DOI PMC

Molleston JM, Cherry S. Attacked from All Sides: RNA Decay in Antiviral Defense. Viruses. 2017;9(1):2. doi: 10.3390/v9010002 PubMed DOI PMC

Bell-Sakyi L, Hartley CS, Khoo JJ, Forth JH, Palomar AM, Makepeace BL. New Cell Lines Derived from European Tick Species. Microorganisms. 2022;10(6):1086. doi: 10.3390/microorganisms10061086 PubMed DOI PMC

De S, Kingan SB, Kitsou C, Portik DM, Foor SD, Frederick JC, et al. A high-quality Ixodes scapularis genome advances tick science. Nat Genet. 2023;55(2):301–11. doi: 10.1038/s41588-022-01275-w PubMed DOI

Kwon SC, Yi H, Eichelbaum K, Föhr S, Fischer B, You KT, et al. The RNA-binding protein repertoire of embryonic stem cells. Nat Struct Mol Biol. 2013;20(9):1122–30. doi: 10.1038/nsmb.2638 PubMed DOI

Despic V, Dejung M, Gu M, Krishnan J, Zhang J, Herzel L, et al. Dynamic RNA-protein interactions underlie the zebrafish maternal-to-zygotic transition. Genome Res. 2017;27(7):1184–94. doi: 10.1101/gr.215954.116 PubMed DOI PMC

Nandan D, Thomas SA, Nguyen A, Moon K-M, Foster LJ, Reiner NE. Comprehensive Identification of mRNA-Binding Proteins of Leishmania donovani by Interactome Capture. PLoS One. 2017;12(1):e0170068. doi: 10.1371/journal.pone.0170068 PubMed DOI PMC

Tsvetanova NG, Klass DM, Salzman J, Brown PO. Proteome-wide search reveals unexpected RNA-binding proteins in Saccharomyces cerevisiae. PLoS One. 2010;5(9):e12671. doi: 10.1371/journal.pone.0012671 PubMed DOI PMC

Marondedze C, Thomas L, Serrano NL, Lilley KS, Gehring C. The RNA-binding protein repertoire of Arabidopsis thaliana. Sci Rep. 2016;6:29766. doi: 10.1038/srep29766 PubMed DOI PMC

Kang D, Gao S, Tian Z, Zhang G, Guan G, Liu G, et al. ISG20 inhibits bluetongue virus replication. Virol Sin. 2022;37(4):521–30. doi: 10.1016/j.virs.2022.04.010 PubMed DOI PMC

Nencioni L, De Chiara G, Sgarbanti R, Amatore D, Aquilano K, Marcocci ME, et al. Bcl-2 expression and p38MAPK activity in cells infected with influenza A virus: impact on virally induced apoptosis and viral replication. J Biol Chem. 2009;284(23):16004–15. doi: 10.1074/jbc.M900146200 PubMed DOI PMC

Shalamova L, Barth P, Pickin MJ, Kouti K, Ott B, Humpert K, et al. Nucleocapsids of the Rift Valley fever virus ambisense S segment contain an exposed RNA element in the center that overlaps with the intergenic region. Nat Commun. 2024;15(1):7602. doi: 10.1038/s41467-024-52058-2 PubMed DOI PMC

Castelló A, Franco D, Moral-López P, Berlanga JJ, Alvarez E, Wimmer E, et al. HIV- 1 protease inhibits Cap- and poly(A)-dependent translation upon eIF4GI and PABP cleavage. PLoS One. 2009;4(11):e7997. doi: 10.1371/journal.pone.0007997 PubMed DOI PMC

Copeland AM, Altamura LA, Van Deusen NM, Schmaljohn CS. Nuclear relocalization of polyadenylate binding protein during rift valley fever virus infection involves expression of the NSs gene. J Virol. 2013;87(21):11659–69. doi: 10.1128/JVI.01434-13 PubMed DOI PMC

Sonenberg N, Hinnebusch AG. Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell. 2009;136(4):731–45. doi: 10.1016/j.cell.2009.01.042 PubMed DOI PMC

Valášek LS, Zeman J, Wagner S, Beznosková P, Pavlíková Z, Mohammad MP, et al. Embraced by eIF3: structural and functional insights into the roles of eIF3 across the translation cycle. Nucleic Acids Res. 2017;45(19):10948–68. doi: 10.1093/nar/gkx805 PubMed DOI PMC

Sun C, Querol-Audí J, Mortimer SA, Arias-Palomo E, Doudna JA, Nogales E, et al. Two RNA-binding motifs in eIF3 direct HCV IRES-dependent translation. Nucleic Acids Res. 2013;41(15):7512–21. doi: 10.1093/nar/gkt510 PubMed DOI PMC

Kerr CH, Ma ZW, Jang CJ, Thompson SR, Jan E. Molecular analysis of the factorless internal ribosome entry site in Cricket Paralysis virus infection. Sci Rep. 2016;6:37319. doi: 10.1038/srep37319 PubMed DOI PMC

Hopkins K, Cherry S. Bunyaviral cap-snatching vs. decapping: recycling cell cycle mRNAs. Cell Cycle. 2013;12(24):3711–2. doi: 10.4161/cc.26878 PubMed DOI PMC

Ho JSY, Angel M, Ma Y, Sloan E, Wang G, Martinez-Romero C, et al. Hybrid Gene Origination Creates Human-Virus Chimeric Proteins during Infection. Cell. 2020;181(7):1502-1517.e23. doi: 10.1016/j.cell.2020.05.035 PubMed DOI PMC

Vera-Otarola J, Castillo-Vargas E, Angulo J, Barriga FM, Batlle E, Lopez-Lastra M. The viral nucleocapsid protein and the human RNA-binding protein Mex3A promote translation of the Andes orthohantavirus small mRNA. PLoS Pathog. 2021;17:e1009931 10.1371/journal.ppat.1009931 PubMed DOI PMC

Salicioni AM, Xi M, Vanderveer LA, Balsara B, Testa JR, Dunbrack RL Jr, et al. Identification and structural analysis of human RBM8A and RBM8B: two highly conserved RNA-binding motif proteins that interact with OVCA1, a candidate tumor suppressor. Genomics. 2000;69(1):54–62. doi: 10.1006/geno.2000.6315 PubMed DOI

Fautsch MP, Wieben ED. Transcriptional regulation of the small nuclear ribonucleoprotein E protein gene. Identification of cis-acting sequences with homology to genes encoding ribosomal proteins. J Biol Chem. 1991;266(34):23288–95. PubMed

Tsuchiya N, Ochiai M, Nakashima K, Ubagai T, Sugimura T, Nakagama H. SND1, a component of RNA-induced silencing complex, is up-regulated in human colon cancers and implicated in early stage colon carcinogenesis. Cancer Res. 2007;67(19):9568–76. doi: 10.1158/0008-5472.CAN-06-2707 PubMed DOI

Castello A, Álvarez L, Kamel W, Iselin L, Hennig J. Exploring the expanding universe of host-virus interactions mediated by viral RNA. Mol Cell. 2024;84(19):3706–21. doi: 10.1016/j.molcel.2024.08.027 PubMed DOI

Schmidt N, Ganskih S, Wei Y, Gabel A, Zielinski S, Keshishian H, et al. SND1 binds SARS-CoV-2 negative-sense RNA and promotes viral RNA synthesis through NSP9. Cell. 2023;186(22):4834-4850.e23. doi: 10.1016/j.cell.2023.09.002 PubMed DOI PMC

Pommier Y, Nussenzweig A, Takeda S, Austin C. Human topoisomerases and their roles in genome stability and organization. Nat Rev Mol Cell Biol. 2022;23(6):407–27. doi: 10.1038/s41580-022-00452-3 PubMed DOI PMC

Ahmad M, Shen W, Li W, Xue Y, Zou S, Xu D, et al. Topoisomerase 3β is the major topoisomerase for mRNAs and linked to neurodevelopment and mental dysfunction. Nucleic Acids Res. 2017;45(5):2704–13. doi: 10.1093/nar/gkw1293 PubMed DOI PMC

Siaw GE-L, Liu I-F, Lin P-Y, Been MD, Hsieh T-S. DNA and RNA topoisomerase activities of Top3β are promoted by mediator protein Tudor domain-containing protein 3. Proc Natl Acad Sci U S A. 2016;113(38):E5544-51. doi: 10.1073/pnas.1605517113 PubMed DOI PMC

Jumper J, Evans R, Pritzel A, Green T, Figurnov M, Ronneberger O, et al. Highly accurate protein structure prediction with AlphaFold. Nature. 2021;596(7873):583–9. doi: 10.1038/s41586-021-03819-2 PubMed DOI PMC

Castello A, Fischer B, Frese CK, Horos R, Alleaume A-M, Foehr S, et al. Comprehensive Identification of RNA-Binding Domains in Human Cells. Mol Cell. 2016;63(4):696–710. doi: 10.1016/j.molcel.2016.06.029 PubMed DOI PMC

Diosa-Toro M, Prasanth KR, Bradrick SS, Garcia Blanco MA. Role of RNA-binding proteins during the late stages of Flavivirus replication cycle. Virol J. 2020;17(1):60. doi: 10.1186/s12985-020-01329-7 PubMed DOI PMC

Xu D, Shen W, Guo R, Xue Y, Peng W, Sima J, et al. Top3β is an RNA topoisomerase that works with fragile X syndrome protein to promote synapse formation. Nat Neurosci. 2013;16(9):1238–47. doi: 10.1038/nn.3479 PubMed DOI PMC

Oliver JD, Chávez ASO, Felsheim RF, Kurtti TJ, Munderloh UG. An Ixodes scapularis cell line with a predominantly neuron-like phenotype. Exp Appl Acarol. 2015;66(3):427–42. doi: 10.1007/s10493-015-9908-1 PubMed DOI PMC

Mateos-Hernández L, Pipová N, Allain E, Henry C, Rouxel C, Lagrée A-C, et al. Enlisting the Ixodes scapularis Embryonic ISE6 Cell Line to Investigate the Neuronal Basis of Tick-Pathogen Interactions. Pathogens. 2021;10(1):70. doi: 10.3390/pathogens10010070 PubMed DOI PMC

Brownsword MJ, Locker N. A little less aggregation a little more replication: Viral manipulation of stress granules. Wiley Interdiscip Rev RNA. 2023;14(1):e1741. doi: 10.1002/wrna.1741 PubMed DOI PMC

Sato M, Maeda N, Yoshida H, Urade M, Saito S. Plaque formation of herpes virus hominis type 2 and rubella virus in variants isolated from the colonies of BHK21/WI-2 cells formed in soft agar. Arch Virol. 1977;53(3):269–73. doi: 10.1007/BF01314672 PubMed DOI

Buchholz UJ, Finke S, Conzelmann KK. Generation of bovine respiratory syncytial virus (BRSV) from cDNA: BRSV NS2 is not essential for virus replication in tissue culture, and the human RSV leader region acts as a functional BRSV genome promoter. J Virol. 1999;73(1):251–9. doi: 10.1128/JVI.73.1.251-259.1999 PubMed DOI PMC

Munderloh UG, Jauron SD, Fingerle V, Leitritz L, Hayes SF, Hautman JM, et al. Invasion and intracellular development of the human granulocytic ehrlichiosis agent in tick cell culture. J Clin Microbiol. 1999;37(8):2518–24. doi: 10.1128/JCM.37.8.2518-2524.1999 PubMed DOI PMC

Persson R, Pettersson RF. Formation and intracellular transport of a heterodimeric viral spike protein complex. J Cell Biol. 1991;112(2):257–66. doi: 10.1083/jcb.112.2.257 PubMed DOI PMC

Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402–8. doi: 10.1006/meth.2001.1262 PubMed DOI

Persson E, Sonnhammer ELL. InParanoid-DIAMOND: faster orthology analysis with the InParanoid algorithm. Bioinformatics. 2022;38(10):2918–9. doi: 10.1093/bioinformatics/btac194 PubMed DOI PMC

Yu G, He Q-Y. ReactomePA: an R/Bioconductor package for reactome pathway analysis and visualization. Mol Biosyst. 2016;12(2):477–9. doi: 10.1039/c5mb00663e PubMed DOI

Mirdita M, Schütze K, Moriwaki Y, Heo L, Ovchinnikov S, Steinegger M. ColabFold: making protein folding accessible to all. Nat Methods. 2022;19(6):679–82. doi: 10.1038/s41592-022-01488-1 PubMed DOI PMC

Meng EC, Goddard TD, Pettersen EF, Couch GS, Pearson ZJ, Morris JH, et al. UCSF ChimeraX: Tools for structure building and analysis. Protein Sci. 2023;32(11):e4792. doi: 10.1002/pro.4792 PubMed DOI PMC

Blum M, Chang H-Y, Chuguransky S, Grego T, Kandasaamy S, Mitchell A, et al. The InterPro protein families and domains database: 20 years on. Nucleic Acids Res. 2021;49(D1):D344–54. doi: 10.1093/nar/gkaa977 PubMed DOI PMC

Madeira F, Madhusoodanan N, Lee J, Eusebi A, Niewielska A, Tivey ARN, et al. The EMBL-EBI Job Dispatcher sequence analysis tools framework in 2024. Nucleic Acids Res. 2024;52(W1):W521–5. doi: 10.1093/nar/gkae241 PubMed DOI PMC