Orthohantaviruses are rodent-borne emerging viruses that may cause severe diseases in humans but no apparent pathology in their small mammal reservoirs. However, the mechanisms leading to tolerance or pathogenicity in humans and persistence in rodent reservoirs are poorly understood, as is the manner in which they spread within and between organisms. Here, we used a range of cellular and molecular approaches to investigate the interactions of three different orthohantaviruses-Puumala virus (PUUV), responsible for a mild to moderate form of hemorrhagic fever with renal syndrome in humans, Tula virus (TULV) with low pathogenicity, and non-pathogenic Prospect Hill virus (PHV)-with human and rodent host cell lines. Besides the fact that cell susceptibility to virus infection was shown to depend on the cell type and virus strain, the three orthohantaviruses were able to infect Vero E6 and HuH7 human cells, but only the former secreted infectious particles. In cells derived from PUUV reservoir, the bank vole (Myodes glareolus), PUUV achieved a complete viral cycle, while TULV did not enter the cells and PHV infected them but did not produce infectious particles, reflecting differences in host specificity. A search for mature virions by electron microscopy (EM) revealed that TULV assembly occurred in part at the plasma membrane, whereas PHV particles were trapped in autophagic vacuoles in cells of the heterologous rodent host. We described differential interactions of orthohantaviruses with cellular factors, as supported by the cellular distribution of viral nucleocapsid protein with cell compartments, and proteomics identification of cellular partners. Our results also showed that interferon (IFN) dependent gene expression was regulated in a cell and virus species dependent manner. Overall, our study highlighted the complexity of the host-virus relationship and demonstrated that orthohantaviruses are restricted at different levels of the viral cycle. In addition, the study opens new avenues to further investigate how these viruses differ in their interactions with cells to evade innate immunity and how it depends on tissue type and host species.

INSERM U1259 et plateforme IBISA de Microscopie Electronique Université et CHRU de Tours Tours France

Institut Pasteur de Guinée Conakry Guinée

Institut Pasteur Université Paris Cité Biomics Platform C2RT Paris France

Institut Pasteur Université Paris Cité Département de Virologie Unité des Stratégies Antivirales Paris France

Institute of Novel and Emerging Infectious Diseases Friedrich Loeffler Institut Partner site Hamburg Lübeck Borstel Riems German Centre for Infection Research Greifswald Insel Riems Germany

Laboratory of Molecular Ecology Institute of Animal Physiology and Genetics Czech Academy of Sciences Liběchov Czech Republic

Sorbonne Université Ecole Doctorale Complexité du Vivant Paris France

Université Paris Cité CNRS Institut Jacques Monod Paris France

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Plyusnin A, Sironen T. Evolution of hantaviruses: co-speciation with reservoir hosts for more than 100 MYR. Virus Res. 2014;187:22–6. Epub 2014/01/28. doi: 10.1016/j.virusres.2014.01.008 . PubMed DOI

Kabwe E, Davidyuk Y, Shamsutdinov A, Garanina E, Martynova E, Kitaeva K, et al.. Orthohantaviruses, Emerging Zoonotic Pathogens. Pathogens. 2020;9(9). Epub 2020/09/26. doi: 10.3390/pathogens9090775 ; PubMed Central PMCID: PMC7558059. PubMed DOI PMC

Raftery MJ, Lalwani P, Lutteke N, Kobak L, Giese T, Ulrich RG, et al.. Replication in the Mononuclear Phagocyte System (MPS) as a Determinant of Hantavirus Pathogenicity. Front Cell Infect Microbiol. 2020;10:281. Epub 2020/07/01. doi: 10.3389/fcimb.2020.00281 ; PubMed Central PMCID: PMC7304325. PubMed DOI PMC

Scholz S, Baharom F, Rankin G, Maleki KT, Gupta S, Vangeti S, et al.. Human hantavirus infection elicits pronounced redistribution of mononuclear phagocytes in peripheral blood and airways. PLoS Pathog. 2017;13(6):e1006462. Epub 2017/06/24. doi: 10.1371/journal.ppat.1006462 ; PubMed Central PMCID: PMC5498053. PubMed DOI PMC

Schonrich G, Raftery MJ. Dendritic Cells (DCs) as "Fire Accelerants" of Hantaviral Pathogenesis. Viruses. 2019;11(9). Epub 2019/09/22. doi: 10.3390/v11090849 ; PubMed Central PMCID: PMC6783833. PubMed DOI PMC

Voutilainen L, Sironen T, Tonteri E, Back AT, Razzauti M, Karlsson M, et al.. Life-long shedding of Puumala hantavirus in wild bank voles (Myodes glareolus). J Gen Virol. 2015;96(Pt 6):1238–47. Epub 2015/02/24. vir.0.000076 [pii] doi: 10.1099/vir.0.000076 . PubMed DOI

Hutchinson KL, Rollin PE, Peters CJ. Pathogenesis of a North American hantavirus, Black Creek Canal virus, in experimentally infected Sigmodon hispidus. Am J Trop Med Hyg. 1998;59(1):58–65. Epub 1998/07/31. doi: 10.4269/ajtmh.1998.59.58 . PubMed DOI

Strandin T, Smura T, Ahola P, Aaltonen K, Sironen T, Hepojoki J, et al.. Orthohantavirus Isolated in Reservoir Host Cells Displays Minimal Genetic Changes and Retains Wild-Type Infection Properties. Viruses. 2020;12(4). Epub 2020/04/23. doi: 10.3390/v12040457 ; PubMed Central PMCID: PMC7232471. PubMed DOI PMC

Schonrich G, Rang A, Lutteke N, Raftery MJ, Charbonnel N, Ulrich RG. Hantavirus-induced immunity in rodent reservoirs and humans. Immunol Rev. 2008;225:163–89. Epub 2008/10/08. doi: 10.1111/j.1600-065X.2008.00694.x . PubMed DOI

Gavrilovskaya IN, Peresleni T, Geimonen E, Mackow ER. Pathogenic hantaviruses selectively inhibit beta3 integrin directed endothelial cell migration. Arch Virol. 2002;147(10):1913–31. Epub 2002/10/12. doi: 10.1007/s00705-002-0852-0 . PubMed DOI

Gavrilovskaya IN, Shepley M, Shaw R, Ginsberg MH, Mackow ER. beta3 Integrins mediate the cellular entry of hantaviruses that cause respiratory failure. Proceedings of the National Academy of Sciences of the United States of America. 1998;95(12):7074–9. Epub 1998/06/17. doi: 10.1073/pnas.95.12.7074 ; PubMed Central PMCID: PMC22743. PubMed DOI PMC

Jangra RK, Herbert AS, Li R, Jae LT, Kleinfelter LM, Slough MM, et al.. Protocadherin-1 is essential for cell entry by New World hantaviruses. Nature. 2018;563(7732):559–63. Epub 2018/11/23. doi: 10.1038/s41586-018-0702-1 ; PubMed Central PMCID: PMC6556216. PubMed DOI PMC

Muller A, Baumann A, Essbauer S, Radosa L, Kruger DH, Witkowski PT, et al.. Analysis of the integrin beta3 receptor for pathogenic orthohantaviruses in rodent host species. Virus Res. 2019;267:36–40. Epub 2019/05/06. doi: 10.1016/j.virusres.2019.04.009 . PubMed DOI

Jin M, Park J, Lee S, Park B, Shin J, Song KJ, et al.. Hantaan virus enters cells by clathrin-dependent receptor-mediated endocytosis. Virology. 2002;294(1):60–9. Epub 2002/03/12. doi: 10.1006/viro.2001.1303 . PubMed DOI

Chiang CF, Flint M, Lin JS, Spiropoulou CF. Endocytic Pathways Used by Andes Virus to Enter Primary Human Lung Endothelial Cells. PLoS One. 2016;11(10):e0164768. Epub 2016/10/26. doi: 10.1371/journal.pone.0164768 ; PubMed Central PMCID: PMC5079659. PubMed DOI PMC

Torriani G, Mayor J, Zimmer G, Kunz S, Rothenberger S, Engler O. Macropinocytosis contributes to hantavirus entry into human airway epithelial cells. Virology. 2019;531:57–68. Epub 2019/03/11. doi: 10.1016/j.virol.2019.02.013 . PubMed DOI

Sperber HS, Welke RW, Petazzi RA, Bergmann R, Schade M, Shai Y, et al.. Self-association and subcellular localization of Puumala hantavirus envelope proteins. Sci Rep. 2019;9(1):707. Epub 2019/01/27. doi: 10.1038/s41598-018-36879-y ; PubMed Central PMCID: PMC6345964. PubMed DOI PMC

Cifuentes-Munoz N, Salazar-Quiroz N, Tischler ND. Hantavirus Gn and Gc envelope glycoproteins: key structural units for virus cell entry and virus assembly. Viruses. 2014;6(4):1801–22. Epub 2014/04/24. doi: 10.3390/v6041801 ; PubMed Central PMCID: PMC4014721. PubMed DOI PMC

Petazzi RA, Koikkarah AA, Tischler ND, Chiantia S. Detection of Envelope Glycoprotein Assembly from Old-World Hantaviruses in the Golgi Apparatus of Living Cells. J Virol. 2020. Epub 2020/11/27. doi: 10.1128/JVI.01238-20 ; PubMed Central PMCID: PMC7851546. PubMed DOI PMC

Ravkov EV, Nichol ST, Compans RW. Polarized entry and release in epithelial cells of Black Creek Canal virus, a New World hantavirus. J Virol. 1997;71(2):1147–54. Epub 1997/02/01. doi: 10.1128/JVI.71.2.1147-1154.1997 ; PubMed Central PMCID: PMC191167. PubMed DOI PMC

Klingstrom J, Ahlm C. Hantavirus protein interactions regulate cellular functions and signaling responses. Expert Rev Anti Infect Ther. 2011;9(1):33–47. Epub 2010/12/22. doi: 10.1586/eri.10.157 . PubMed DOI

Ramanathan HN, Chung DH, Plane SJ, Sztul E, Chu YK, Guttieri MC, et al.. Dynein-dependent transport of the hantaan virus nucleocapsid protein to the endoplasmic reticulum-Golgi intermediate compartment. J Virol. 2007;81(16):8634–47. Epub 2007/06/01. doi: 10.1128/JVI.00418-07 ; PubMed Central PMCID: PMC1951367. PubMed DOI PMC

Mir MA, Duran WA, Hjelle BL, Ye C, Panganiban AT. Storage of cellular 5’ mRNA caps in P bodies for viral cap-snatching. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(49):19294–9. Epub 2008/12/03. doi: 10.1073/pnas.0807211105 ; PubMed Central PMCID: PMC2614755. PubMed DOI PMC

Li XD, Makela TP, Guo D, Soliymani R, Koistinen V, Vapalahti O, et al.. Hantavirus nucleocapsid protein interacts with the Fas-mediated apoptosis enhancer Daxx. J Gen Virol. 2002;83(Pt 4):759–66. Epub 2002/03/22. doi: 10.1099/0022-1317-83-4-759 . PubMed DOI

Ontiveros SJ, Li Q, Jonsson CB. Modulation of apoptosis and immune signaling pathways by the Hantaan virus nucleocapsid protein. Virology. 2010;401(2):165–78. Epub 2010/03/17. doi: 10.1016/j.virol.2010.02.018 ; PubMed Central PMCID: PMC5653253. PubMed DOI PMC

Park SW, Han MG, Park C, Ju YR, Ahn BY, Ryou J. Hantaan virus nucleocapsid protein stimulates MDM2-dependent p53 degradation. J Gen Virol. 2013;94(Pt 11):2424–8. Epub 2013/09/03. doi: 10.1099/vir.0.054312-0 ; PubMed Central PMCID: PMC4093783. PubMed DOI PMC

Ramanathan HN, Jonsson CB. New and Old World hantaviruses differentially utilize host cytoskeletal components during their life cycles. Virology. 2008;374(1):138–50. Epub 2008/02/01. doi: 10.1016/j.virol.2007.12.030 . PubMed DOI

Alff PJ, Gavrilovskaya IN, Gorbunova E, Endriss K, Chong Y, Geimonen E, et al.. The pathogenic NY-1 hantavirus G1 cytoplasmic tail inhibits RIG-I- and TBK-1-directed interferon responses. J Virol. 2006;80(19):9676–86. Epub 2006/09/16. doi: 10.1128/JVI.00508-06 ; PubMed Central PMCID: PMC1617216. PubMed DOI PMC

Matthys V, Gorbunova EE, Gavrilovskaya IN, Pepini T, Mackow ER. The C-terminal 42 residues of the Tula virus Gn protein regulate interferon induction. J Virol. 2011;85(10):4752–60. Epub 2011/03/04. doi: 10.1128/JVI.01945-10 ; PubMed Central PMCID: PMC3126157. PubMed DOI PMC

Gallo G, Caignard G, Badonnel K, Chevreux G, Terrier S, Szemiel A, et al.. Interactions of Viral Proteins from Pathogenic and Low or Non-Pathogenic Orthohantaviruses with Human Type I Interferon Signaling. Viruses. 2021;13(1). Epub 2021/01/23. doi: 10.3390/v13010140 ; PubMed Central PMCID: PMC7835746. PubMed DOI PMC

Matthys VS, Cimica V, Dalrymple NA, Glennon NB, Bianco C, Mackow ER. Hantavirus GnT elements mediate TRAF3 binding and inhibit RIG-I/TBK1-directed beta interferon transcription by blocking IRF3 phosphorylation. J Virol. 2014;88(4):2246–59. Epub 2014/01/07. JVI.02647-13 [pii] doi: 10.1128/JVI.02647-13 ; PubMed Central PMCID: PMC3911538. PubMed DOI PMC

Ermonval M, Baychelier F, Tordo N. What Do We Know about How Hantaviruses Interact with Their Different Hosts? Viruses. 2016;8(8). Epub 2016/08/17. doi: 10.3390/v8080223 ; PubMed Central PMCID: PMC4997585. PubMed DOI PMC

Easterbrook JD, Klein SL. Immunological mechanisms mediating hantavirus persistence in rodent reservoirs. PLoS Pathog. 2008;4(11):e1000172. Epub 2008/12/02. doi: 10.1371/journal.ppat.1000172 ; PubMed Central PMCID: PMC2584234. PubMed DOI PMC

Safronetz D, Zivcec M, Lacasse R, Feldmann F, Rosenke R, Long D, et al.. Pathogenesis and host response in Syrian hamsters following intranasal infection with Andes virus. PLoS Pathog. 2011;7(12):e1002426. Epub 2011/12/24. doi: 10.1371/journal.ppat.1002426 ; PubMed Central PMCID: PMC3240607. PubMed DOI PMC

Jiang H, Du H, Wang LM, Wang PZ, Bai XF. Hemorrhagic Fever with Renal Syndrome: Pathogenesis and Clinical Picture. Front Cell Infect Microbiol. 2016;6:1. Epub 2016/02/13. doi: 10.3389/fcimb.2016.00001 ; PubMed Central PMCID: PMC4737898. PubMed DOI PMC

Schmidt-Chanasit J, Essbauer S, Petraityte R, Yoshimatsu K, Tackmann K, Conraths FJ, et al.. Extensive host sharing of central European Tula virus. J Virol. 2010;84(1):459–74. Epub 2009/11/06. doi: 10.1128/JVI.01226-09 ; PubMed Central PMCID: PMC2798396. PubMed DOI PMC

Hofmann J, Kramer S, Herrlinger KR, Jeske K, Kuhns M, Weiss S, et al.. Tula Virus as Causative Agent of Hantavirus Disease in Immunocompetent Person, Germany. Emerg Infect Dis. 2021;27(4):1234–7. Epub 2021/03/24. doi: 10.3201/eid2704.203996 ; PubMed Central PMCID: PMC8007307. PubMed DOI PMC

Reynes JM, Carli D, Boukezia N, Debruyne M, Herti S. Tula hantavirus infection in a hospitalised patient, France, June 2015. Euro Surveill. 2015;20(50). Epub 2015/12/23. doi: 10.2807/1560-7917.ES.2015.20.50.30095 . PubMed DOI

Eckerle I, Lenk M, Ulrich RG. More novel hantaviruses and diversifying reservoir hosts—time for development of reservoir-derived cell culture models? Viruses. 2014;6(3):951–67. Epub 2014/03/01. v6030951 [pii] doi: 10.3390/v6030951 ; PubMed Central PMCID: PMC3970132. PubMed DOI PMC

Essbauer SS, Krautkramer E, Herzog S, Pfeffer M. A new permanent cell line derived from the bank vole (Myodes glareolus) as cell culture model for zoonotic viruses. Virol J. 2011;8:339. Epub 2011/07/07. doi: 10.1186/1743-422X-8-339 ; PubMed Central PMCID: PMC3145595. PubMed DOI PMC

Barriga GP, Martinez-Valdebenito C, Galeno H, Ferres M, Lozach PY, Tischler ND. A rapid method for infectivity titration of Andes hantavirus using flow cytometry. J Virol Methods. 2013;193(2):291–4. Epub 2013/06/29. doi: 10.1016/j.jviromet.2013.06.022 . PubMed DOI

Prescott J, Hall P, Acuna-Retamar M, Ye C, Wathelet MG, Ebihara H, et al.. New World hantaviruses activate IFNlambda production in type I IFN-deficient vero E6 cells. PLoS One. 2010;5(6):e11159. Epub 2010/06/23. doi: 10.1371/journal.pone.0011159 ; PubMed Central PMCID: PMC2887373. PubMed DOI PMC

Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. 1990;215(3):403–10. Epub 1990/10/05. doi: 10.1016/S0022-2836(05)80360-2 . PubMed DOI

Kotlik P, Markova S, Konczal M, Babik W, Searle JB. Genomics of end-Pleistocene population replacement in a small mammal. Proc Biol Sci. 2018;285(1872). Epub 2018/02/14. doi: 10.1098/rspb.2017.2624 ; PubMed Central PMCID: PMC5829201. PubMed DOI PMC

Perez-Riverol Y, Bai J, Bandla C, Garcia-Seisdedos D, Hewapathirana S, Kamatchinathan S, et al.. The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences. Nucleic Acids Res. 2022;50(D1):D543–D52. Epub 2021/11/02. doi: 10.1093/nar/gkab1038 ; PubMed Central PMCID: PMC8728295. PubMed DOI PMC

Cokelaer T, Desvillechabrol D, Legendre R, Cardon M. ‘Sequana’: a Set of Snakemake NGS pipelines. JOSS. 2017;2(16):352. doi: 10.21105/joss.00352 DOI

Koster J, Rahmann S. Snakemake—a scalable bioinformatics workflow engine. Bioinformatics. 2012;28(19):2520–2. Epub 2012/08/22. doi: 10.1093/bioinformatics/bts480 . PubMed DOI

Martin M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet journal. 2011;17(1). 10.14806/ej.17.1.200. DOI

Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, et al.. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29(1):15–21. Epub 2012/10/30. doi: 10.1093/bioinformatics/bts635 ; PubMed Central PMCID: PMC3530905. PubMed DOI PMC

Kotlik P, Markova S, White TA, Searle JB. Chromosome-level assembly of the bank vole Myodes glareolus genome. in preparation.

Liao Y, Smyth GK, Shi W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics. 2014;30(7):923–30. Epub 2013/11/15. doi: 10.1093/bioinformatics/btt656 . PubMed DOI

Ewels P, Magnusson M, Lundin S, Kaller M. MultiQC: summarize analysis results for multiple tools and samples in a single report. Bioinformatics. 2016;32(19):3047–8. Epub 2016/06/18. doi: 10.1093/bioinformatics/btw354 ; PubMed Central PMCID: PMC5039924. PubMed DOI PMC

Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550. Epub 2014/12/18. doi: 10.1186/s13059-014-0550-8 ; PubMed Central PMCID: PMC4302049. PubMed DOI PMC

Varet H, Brillet-Gueguen L, Coppee JY, Dillies MA. SARTools: A DESeq2- and EdgeR-Based R Pipeline for Comprehensive Differential Analysis of RNA-Seq Data. PLoS One. 2016;11(6):e0157022. Epub 2016/06/10. doi: 10.1371/journal.pone.0157022 ; PubMed Central PMCID: PMC4900645. PubMed DOI PMC

Mi H, Muruganujan A, Ebert D, Huang X, Thomas PD. PANTHER version 14: more genomes, a new PANTHER GO-slim and improvements in enrichment analysis tools. Nucleic Acids Res. 2019;47(D1):D419–D26. Epub 2018/11/09. doi: 10.1093/nar/gky1038 ; PubMed Central PMCID: PMC6323939. PubMed DOI PMC

Huntley RP, Sawford T, Mutowo-Meullenet P, Shypitsyna A, Bonilla C, Martin MJ, et al.. The GOA database: gene Ontology annotation updates for 2015. Nucleic Acids Res. 2015;43(Database issue):D1057–63. Epub 2014/11/08. doi: 10.1093/nar/gku1113 ; PubMed Central PMCID: PMC4383930. PubMed DOI PMC

Chen EY, Tan CM, Kou Y, Duan Q, Wang Z, Meirelles GV, et al.. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics. 2013;14:128. Epub 2013/04/17. doi: 10.1186/1471-2105-14-128 ; PubMed Central PMCID: PMC3637064. PubMed DOI PMC

Kanehisa M, Goto S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 2000;28(1):27–30. Epub 1999/12/11. doi: 10.1093/nar/28.1.27 ; PubMed Central PMCID: PMC102409. PubMed DOI PMC

Cokelaer T, Pultz D, Harder LM, Serra-Musach J, Saez-Rodriguez J. BioServices: a common Python package to access biological Web Services programmatically. Bioinformatics. 2013;29(24):3241–2. Epub 2013/09/26. doi: 10.1093/bioinformatics/btt547 ; PubMed Central PMCID: PMC3842755. PubMed DOI PMC

Davies KA, Chadwick B, Hewson R, Fontana J, Mankouri J, Barr JN. The RNA Replication Site of Tula Orthohantavirus Resides within a Remodelled Golgi Network. Cells. 2020;9(7). Epub 2020/07/02. doi: 10.3390/cells9071569 ; PubMed Central PMCID: PMC7408811. PubMed DOI PMC

Rowe RK, Suszko JW, Pekosz A. Roles for the recycling endosome, Rab8, and Rab11 in hantavirus release from epithelial cells. Virology. 2008;382(2):239–49. Epub 2008/10/28. doi: 10.1016/j.virol.2008.09.021 ; PubMed Central PMCID: PMC2648827. PubMed DOI PMC

Nourbakhsh M, Kalble S, Dorrie A, Hauser H, Resch K, Kracht M. The NF-kappa b repressing factor is involved in basal repression and interleukin (IL)-1-induced activation of IL-8 transcription by binding to a conserved NF-kappa b-flanking sequence element. J Biol Chem. 2001;276(6):4501–8. Epub 2000/11/10. doi: 10.1074/jbc.M007532200 . PubMed DOI

Hagele S, Nusshag C, Muller A, Baumann A, Zeier M, Krautkramer E. Cells of the human respiratory tract support the replication of pathogenic Old World orthohantavirus Puumala. Virol J. 2021;18(1):169. Epub 2021/08/19. doi: 10.1186/s12985-021-01636-7 ; PubMed Central PMCID: PMC8369447. PubMed DOI PMC

Noack D, Goeijenbier M, Reusken C, Koopmans MPG, Rockx BHG. Orthohantavirus Pathogenesis and Cell Tropism. Front Cell Infect Microbiol. 2020;10:399. Epub 2020/09/10. doi: 10.3389/fcimb.2020.00399 ; PubMed Central PMCID: PMC7438779. PubMed DOI PMC

Hagele S, Muller A, Nusshag C, Reiser J, Zeier M, Krautkramer E. Virus- and cell type-specific effects in orthohantavirus infection. Virus Res. 2019;260:102–13. Epub 2018/12/07. doi: 10.1016/j.virusres.2018.11.015 . PubMed DOI

Temonen M, Vapalahti O, Holthofer H, Brummer-Korvenkontio M, Vaheri A, Lankinen H. Susceptibility of human cells to Puumala virus infection. J Gen Virol. 1993;74 (Pt 3):515–8. Epub 1993/03/01. doi: 10.1099/0022-1317-74-3-515 . PubMed DOI

Binder F, Lenk M, Weber S, Stoek F, Dill V, Reiche S, et al.. Common vole (Microtus arvalis) and bank vole (Myodes glareolus) derived permanent cell lines differ in their susceptibility and replication kinetics of animal and zoonotic viruses. J Virol Methods. 2019;274:113729. Epub 2019/09/13. doi: 10.1016/j.jviromet.2019.113729 . PubMed DOI

Goldsmith CS, Elliott LH, Peters CJ, Zaki SR. Ultrastructural characteristics of Sin Nombre virus, causative agent of hantavirus pulmonary syndrome. Arch Virol. 1995;140(12):2107–22. doi: 10.1007/BF01323234 . PubMed DOI

Andreu-Moreno I, Sanjuan R. Collective Infection of Cells by Viral Aggregates Promotes Early Viral Proliferation and Reveals a Cellular-Level Allee Effect. Curr Biol. 2018;28(20):3212–9 e4. Epub 2018/10/16. doi: 10.1016/j.cub.2018.08.028 ; PubMed Central PMCID: PMC6783297. PubMed DOI PMC

Parvate A, Williams EP, Taylor MK, Chu YK, Lanman J, Saphire EO, et al.. Diverse Morphology and Structural Features of Old and New World Hantaviruses. Viruses. 2019;11(9). Epub 2019/09/19. doi: 10.3390/v11090862 ; PubMed Central PMCID: PMC6783877. PubMed DOI PMC

Parvate AD, Vago F, Hasan SS, Lee J, Williams EP, Lanman J, et al.. A new inactivation method to facilitate cryo-EM of enveloped, RNA viruses requiring high containment: A case study using Venezuelan Equine Encephalitis Virus (VEEV). J Virol Methods. 2020;277:113792. Epub 2019/12/02. doi: 10.1016/j.jviromet.2019.113792 . PubMed DOI

Robinson M, Schor S, Barouch-Bentov R, Einav S. Viral journeys on the intracellular highways. Cell Mol Life Sci. 2018;75(20):3693–714. Epub 2018/07/26. doi: 10.1007/s00018-018-2882-0 ; PubMed Central PMCID: PMC6151136. PubMed DOI PMC

Reuter M, Kruger DH. The nucleocapsid protein of hantaviruses: much more than a genome-wrapping protein. Virus Genes. 2018;54(1):5–16. Epub 2017/11/22. doi: 10.1007/s11262-017-1522-3 . PubMed DOI

Christ W, Tynell J, Klingstrom J. Puumala and Andes Orthohantaviruses Cause Transient Protein Kinase R-Dependent Formation of Stress Granules. J Virol. 2020;94(3). Epub 2019/11/15. doi: 10.1128/JVI.01168-19 ; PubMed Central PMCID: PMC7000972. PubMed DOI PMC

Ravkov EV, Nichol ST, Peters CJ, Compans RW. Role of actin microfilaments in Black Creek Canal virus morphogenesis. J Virol. 1998;72(4):2865–70. Epub 1998/04/03. doi: 10.1128/JVI.72.4.2865-2870.1998 ; PubMed Central PMCID: PMC109731. PubMed DOI PMC

Wang K, Ma H, Liu H, Ye W, Li Z, Cheng L, et al.. The Glycoprotein and Nucleocapsid Protein of Hantaviruses Manipulate Autophagy Flux to Restrain Host Innate Immune Responses. Cell Rep. 2019;27(7):2075–91 e5. Epub 2019/05/16. doi: 10.1016/j.celrep.2019.04.061 . PubMed DOI

Welke RW, Sperber HS, Bergmann R, Koikkarah A, Menke L, Sieben C, et al.. Characterization of Hantavirus N Protein Intracellular Dynamics and Localization. Viruses. 2022;14(3). Epub 2022/03/27. doi: 10.3390/v14030457 ; PubMed Central PMCID: PMC8954124. PubMed DOI PMC

Bosch M, Sanchez-Alvarez M, Fajardo A, Kapetanovic R, Steiner B, Dutra F, et al.. Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense. Science. 2020;370(6514). Epub 2020/10/17. doi: 10.1126/science.aay8085 . PubMed DOI

Tzeng HT, Chyuan IT, Chen WY. Shaping of Innate Immune Response by Fatty Acid Metabolite Palmitate. Cells. 2019;8(12). Epub 2019/12/19. doi: 10.3390/cells8121633 ; PubMed Central PMCID: PMC6952933. PubMed DOI PMC

Ohol YM, Wang Z, Kemble G, Duke G. Direct Inhibition of Cellular Fatty Acid Synthase Impairs Replication of Respiratory Syncytial Virus and Other Respiratory Viruses. PLoS One. 2015;10(12):e0144648. Epub 2015/12/15. doi: 10.1371/journal.pone.0144648 ; PubMed Central PMCID: PMC4684246. PubMed DOI PMC

Tongluan N, Ramphan S, Wintachai P, Jaresitthikunchai J, Khongwichit S, Wikan N, et al.. Involvement of fatty acid synthase in dengue virus infection. Virol J. 2017;14(1):28. Epub 2017/02/15. doi: 10.1186/s12985-017-0685-9 ; PubMed Central PMCID: PMC5307738. PubMed DOI PMC

Spengler JR, Haddock E, Gardner D, Hjelle B, Feldmann H, Prescott J. Experimental Andes virus infection in deer mice: characteristics of infection and clearance in a heterologous rodent host. PLoS One. 2013;8(1):e55310. Epub 2013/02/06. doi: 10.1371/journal.pone.0055310 ; PubMed Central PMCID: PMC3561286. PubMed DOI PMC

Brocato RL, Altamura LA, Carey BD, Perley CC, Blancett CD, Minogue TD, et al.. Comparison of transcriptional responses between pathogenic and nonpathogenic hantavirus infections in Syrian hamsters using NanoString. PLoS Negl Trop Dis. 2021;15(8):e0009592. Epub 2021/08/03. doi: 10.1371/journal.pntd.0009592 ; PubMed Central PMCID: PMC8360559. PubMed DOI PMC