{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:24:42Z","timestamp":1791260682031,"version":"4.1.0"},"reference-count":109,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Academic Exchange Service (DAAD)","award":["57320205"],"award-info":[{"award-number":["57320205"]}]},{"name":"Open Access funding","award":["Projekt DEAL"],"award-info":[{"award-number":["Projekt DEAL"]}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2017-05607"],"award-info":[{"award-number":["2017-05607"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Wenner-Grens foundations postdoctoral fellowship","award":["UPD2018-0193"],"award-info":[{"award-number":["UPD2018-0193"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Chikungunya virus (CHIKV) is a re-emerging, mosquito-transmitted, enveloped positive stranded RNA virus. Chikungunya fever is characterized by acute and chronic debilitating arthritis. Although multiple host factors have been shown to enhance CHIKV infection, the molecular mechanisms of cell entry and entry factors remain poorly understood. The phosphatidylserine-dependent receptors, T-cell immunoglobulin and mucin domain 1 (TIM-1) and Axl receptor tyrosine kinase (Axl), are transmembrane proteins that can serve as entry factors for enveloped viruses. Previous studies used pseudoviruses to delineate the role of TIM-1 and Axl in CHIKV entry. Conversely, here, we use the authentic CHIKV and cells ectopically expressing TIM-1 or Axl and demonstrate a role for TIM-1 in CHIKV infection. To further characterize TIM-1-dependent CHIKV infection, we generated cells expressing domain mutants of TIM-1. We show that point mutations in the phosphatidylserine binding site of TIM-1 lead to reduced cell binding, entry, and infection of CHIKV. Ectopic expression of TIM-1 renders immortalized keratinocytes permissive to CHIKV, whereas silencing of endogenously expressed TIM-1 in human hepatoma cells reduces CHIKV infection. Altogether, our findings indicate that, unlike Axl, TIM-1 readily promotes the productive entry of authentic CHIKV into target cells.<\/jats:p>","DOI":"10.3390\/cells10071828","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T05:10:59Z","timestamp":1626757859000},"page":"1828","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["The Phosphatidylserine Receptor TIM-1 Enhances Authentic Chikungunya Virus Cell Entry"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1741-7606","authenticated-orcid":false,"given":"Jared","family":"Kirui","sequence":"first","affiliation":[{"name":"Centre for Experimental and Clinical Infection Research, TWINCORE, Institute for Experimental Virology, a Joint Venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, 30625 Hannover, Germany"},{"name":"Department of Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1612-7247","authenticated-orcid":false,"given":"Yara","family":"Abidine","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Ume\u00e5 University, 90185 Ume\u00e5, Sweden"},{"name":"Wallenberg Centre for Molecular Medicine (WCMM), Ume\u00e5 University, 90185 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5109-9408","authenticated-orcid":false,"given":"Annasara","family":"Lenman","sequence":"additional","affiliation":[{"name":"Centre for Experimental and Clinical Infection Research, TWINCORE, Institute for Experimental Virology, a Joint Venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, 30625 Hannover, Germany"},{"name":"Department of Clinical Microbiology, Ume\u00e5 University, 90185 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koushikul","family":"Islam","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Ume\u00e5 University, 90185 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0703-4188","authenticated-orcid":false,"given":"Yong-Dae","family":"Gwon","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Ume\u00e5 University, 90185 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0393-076X","authenticated-orcid":false,"given":"Lisa","family":"Lasswitz","sequence":"additional","affiliation":[{"name":"Centre for Experimental and Clinical Infection Research, TWINCORE, Institute for Experimental Virology, a Joint Venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, 30625 Hannover, Germany"},{"name":"Department of Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Evander","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Ume\u00e5 University, 90185 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5865-8302","authenticated-orcid":false,"given":"Marta","family":"Bally","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Ume\u00e5 University, 90185 Ume\u00e5, Sweden"},{"name":"Wallenberg Centre for Molecular Medicine (WCMM), Ume\u00e5 University, 90185 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1326-5038","authenticated-orcid":false,"given":"Gisa","family":"Gerold","sequence":"additional","affiliation":[{"name":"Centre for Experimental and Clinical Infection Research, TWINCORE, Institute for Experimental Virology, a Joint Venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, 30625 Hannover, Germany"},{"name":"Department of Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, 30559 Hannover, Germany"},{"name":"Department of Clinical Microbiology, Ume\u00e5 University, 90185 Ume\u00e5, Sweden"},{"name":"Wallenberg Centre for Molecular Medicine (WCMM), Ume\u00e5 University, 90185 Ume\u00e5, 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Virol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.ijid.2017.03.006","article-title":"Global expansion of chikungunya virus: Mapping the 64-year history","volume":"58","author":"Wahid","year":"2017","journal-title":"Int. J. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Tsetsarkin, K.A., Vanlandingham, D.L., McGee, C.E., and Higgs, S. (2007). A single mutation in chikungunya virus affects vector specificity and epidemic potential. PLoS Pathog., 3.","DOI":"10.1371\/journal.ppat.0030201"},{"key":"ref_4","first-page":"471","article-title":"Re-emergence of Chikungunya and O\u2019nyong-nyong viruses: Evidence for distinct geographical lineages and distant evolutionary relationships","volume":"81","author":"Powers","year":"2000","journal-title":"J. Gen. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.antiviral.2013.06.009","article-title":"Chikungunya fever: Epidemiology, clinical syndrome, pathogenesis and therapy","volume":"99","author":"Thiberville","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Dupuis-Maguiraga, L., Noret, M., Brun, S., Le Grand, R., Gras, G., and Roques, P. (2012). Chikungunya disease: Infection-associated markers from the acute to the chronic phase of arbovirus-induced arthralgia. PLoS Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001446"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3647","DOI":"10.3390\/v7072792","article-title":"Early Events in Chikungunya Virus Infection-From Virus Cell Binding to Membrane Fusion","volume":"7","author":"Hoornweg","year":"2015","journal-title":"Viruses"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Sourisseau, M., Schilte, C., Casartelli, N., Trouillet, C., Guivel-Benhassine, F., Rudnicka, D., Sol-Foulon, N., Le Roux, K., Prevost, M.-C., and Fsihi, H. (2007). Characterization of reemerging chikungunya virus. PLoS Pathog., 3.","DOI":"10.1371\/journal.ppat.0030089"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.virol.2009.07.024","article-title":"Replication cycle of chikungunya: A re-emerging arbovirus","volume":"393","author":"Solignat","year":"2009","journal-title":"Virology"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Wikan, N., Sakoonwatanyoo, P., Ubol, S., Yoksan, S., and Smith, D.R. (2012). Chikungunya virus infection of cell lines: Analysis of the East, Central and South African lineage. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0031102"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1586\/erv.12.84","article-title":"Chikungunya virus and prospects for a vaccine","volume":"11","author":"Weaver","year":"2012","journal-title":"Expert Rev. Vaccines"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Schnierle, B.S. (2019). Cellular attachment and entry factors for chikungunya virus. Viruses, 11.","DOI":"10.3390\/v11111078"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Holmes, A.C., Basore, K., Fremont, D.H., and Diamond, M.S. (2020). A molecular understanding of alphavirus entry. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008876"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3353","DOI":"10.1007\/s00705-014-2210-4","article-title":"Involvement of ATP synthase \u03b2 subunit in chikungunya virus entry into insect cells","volume":"159","author":"Fongsaran","year":"2014","journal-title":"Arch. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1002\/jmv.23403","article-title":"Identification of prohibitin as a Chikungunya virus receptor protein","volume":"84","author":"Wintachai","year":"2012","journal-title":"J. Med. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Gardner, C.L., Hritz, J., Sun, C., Vanlandingham, D.L., Song, T.Y., Ghedin, E., Higgs, S., Klimstra, W.B., and Ryman, K.D. (2014). Deliberate attenuation of chikungunya virus by adaptation to heparan sulfate-dependent infectivity: A model for rational arboviral vaccine design. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0002719"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1128\/JVI.03116-13","article-title":"A single-amino-acid polymorphism in Chikungunya virus E2 glycoprotein influences glycosaminoglycan utilization","volume":"88","author":"Silva","year":"2014","journal-title":"J. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8327","DOI":"10.1128\/JVI.01025-13","article-title":"Role of the phosphatidylserine receptor TIM-1 in enveloped-virus entry","volume":"87","author":"Kondratowicz","year":"2013","journal-title":"J. Virol."},{"key":"ref_19","first-page":"565","article-title":"Phosphatidylserine receptors: Enhancers of enveloped virus entry and infection","volume":"468","author":"Maury","year":"2014","journal-title":"Virology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1038\/s41586-018-0121-3","article-title":"Mxra8 is a receptor for multiple arthritogenic alphaviruses","volume":"557","author":"Zhang","year":"2018","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Weber, C., Berberich, E., von Rhein, C., Hen\u00df, L., Hildt, E., and Schnierle, B.S. (2017). Identification of functional determinants in the chikungunya virus E2 protein. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005318"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1016\/j.cell.2019.04.006","article-title":"Cryo-EM Structure of Chikungunya Virus in Complex with the Mxra8 Receptor","volume":"177","author":"Basore","year":"2019","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1016\/j.cell.2019.04.008","article-title":"Molecular basis of arthritogenic alphavirus receptor MXRA8 binding to chikungunya virus envelope protein","volume":"177","author":"Song","year":"2019","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.immuni.2011.09.004","article-title":"Beginnings of a good apoptotic meal: The find-me and eat-me signaling pathways","volume":"35","author":"Ravichandran","year":"2011","journal-title":"Immunity"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1093\/intimm\/dxs161","article-title":"Pyroptotic cells externalize eat-me and release find-me signals and are efficiently engulfed by macrophages","volume":"25","author":"Wang","year":"2013","journal-title":"Int. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.jim.2015.04.025","article-title":"Quantification of apoptosis and necroptosis at the single cell level by a combination of Imaging Flow Cytometry with classical Annexin V\/propidium iodide staining","volume":"423","author":"Pietkiewicz","year":"2015","journal-title":"J. Immunol. Methods"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2","DOI":"10.2353\/ajpath.2007.070135","article-title":"Immunological consequences of apoptotic cell phagocytosis","volume":"171","author":"Erwig","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1172\/JCI34487","article-title":"Kidney injury molecule-1 is a phosphatidylserine receptor that confers a phagocytic phenotype on epithelial cells","volume":"118","author":"Ichimura","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.15252\/embj.201489838","article-title":"KIM-1-\/TIM-1-mediated phagocytosis links ATG5-\/ULK1-dependent clearance of apoptotic cells to antigen presentation","volume":"34","author":"Brooks","year":"2015","journal-title":"EMBO J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/j.1749-6632.2010.05772.x","article-title":"Apoptotic mimicry: Phosphatidylserine-mediated macropinocytosis of vaccinia virus","volume":"1209","author":"Mercer","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/nrmicro3469","article-title":"Viral apoptotic mimicry","volume":"13","author":"Amara","year":"2015","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Niu, J., Jiang, Y., Xu, H., Zhao, C., Zhou, G., Chen, P., and Cao, R. (2018). TIM-1 Promotes Japanese Encephalitis Virus Entry and Infection. Viruses, 10.","DOI":"10.3390\/v10110630"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Jemielity, S., Wang, J.J., Chan, Y.K., Ahmed, A.A., Li, W., Monahan, S., Bu, X., Farzan, M., Freeman, G.J., and Umetsu, D.T. (2013). TIM-family proteins promote infection of multiple enveloped viruses through virion-associated phosphatidylserine. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003232"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.chom.2012.08.009","article-title":"The TIM and TAM families of phosphatidylserine receptors mediate dengue virus entry","volume":"12","author":"Meertens","year":"2012","journal-title":"Cell Host Microbe"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"30022","DOI":"10.1074\/jbc.271.47.30022","article-title":"Identification of the product of growth arrest-specific gene 6 as a common ligand for Axl, Sky, and Mer receptor tyrosine kinases","volume":"271","author":"Nagata","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/ni871","article-title":"Serum-derived protein S binds to phosphatidylserine and stimulates the phagocytosis of apoptotic cells","volume":"4","author":"Anderson","year":"2003","journal-title":"Nat. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1016\/j.celrep.2018.04.013","article-title":"TIM-1 Ubiquitination Mediates Dengue Virus Entry","volume":"23","author":"Dejarnac","year":"2018","journal-title":"Cell Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1084\/jem.20120493","article-title":"Identification of Axl as a downstream effector of TGF-\u03b21 during Langerhans cell differentiation and epidermal homeostasis","volume":"209","author":"Bauer","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1083\/jcb.106.3.761","article-title":"Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line","volume":"106","author":"Boukamp","year":"1988","journal-title":"J. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4745","DOI":"10.1128\/JVI.03184-15","article-title":"Dynamics of Chikungunya Virus Cell Entry Unraveled by Single-Virus Tracking in Living Cells","volume":"90","author":"Hoornweg","year":"2016","journal-title":"J. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Ooi, Y.S., Stiles, K.M., Liu, C.Y., Taylor, G.M., and Kielian, M. (2013). Genome-wide RNAi screen identifies novel host proteins required for alphavirus entry. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003835"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Bernard, E., Solignat, M., Gay, B., Chazal, N., Higgs, S., Devaux, C., and Briant, L. (2010). Endocytosis of chikungunya virus into mammalian cells: Role of clathrin and early endosomal compartments. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011479"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Lee, R.C.H., Hapuarachchi, H.C., Chen, K.C., Hussain, K.M., Chen, H., Low, S.L., Ng, L.C., Lin, R., Ng, M.M.-L., and Chu, J.J.H. (2013). Mosquito cellular factors and functions in mediating the infectious entry of chikungunya virus. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002050"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/1423-0127-19-44","article-title":"Cell-based analysis of Chikungunya virus E1 protein in membrane fusion","volume":"19","author":"Kuo","year":"2012","journal-title":"J. Biomed. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.jviromet.2011.05.015","article-title":"Cell-based analysis of Chikungunya virus membrane fusion using baculovirus-expression vectors","volume":"175","author":"Kuo","year":"2011","journal-title":"J. Virol. Methods"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1099\/vir.0.000144","article-title":"Chikungunya virus fusion properties elucidated by single-particle and bulk approaches","volume":"96","author":"Blijleven","year":"2015","journal-title":"J. Gen. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.1073\/pnas.1414190112","article-title":"Residue-level resolution of alphavirus envelope protein interactions in pH-dependent fusion","volume":"112","author":"Zeng","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","first-page":"379","article-title":"Analysis of mutation in human cells by using an Epstein-Barr virus shuttle system","volume":"7","author":"DuBridge","year":"1987","journal-title":"Mol. Cell. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"13001","DOI":"10.1128\/JVI.76.24.13001-13014.2002","article-title":"Highly permissive cell lines for subgenomic and genomic hepatitis C virus RNA replication","volume":"76","author":"Blight","year":"2002","journal-title":"J. Virol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1089\/vbz.2006.6.325","article-title":"Infectious clones of Chikungunya virus (La R\u00e9union isolate) for vector competence studies","volume":"6","author":"Tsetsarkin","year":"2006","journal-title":"Vector Borne Zoonotic Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1016\/j.ibmb.2005.05.008","article-title":"Development and characterization of a double subgenomic chikungunya virus infectious clone to express heterologous genes in Aedes aegypti mosquitoes","volume":"35","author":"Vanlandingham","year":"2005","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/0264-410X(86)90003-4","article-title":"Development of an attenuated strain of chikungunya virus for use in vaccine production","volume":"4","author":"Levitt","year":"1986","journal-title":"Vaccine"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Jin, J., Sherman, M.B., Chafets, D., Dinglasan, N., Lu, K., Lee, T.-H., Carlson, L.-A., Muench, M.O., and Simmons, G. (2018). An attenuated replication-competent chikungunya virus with a fluorescently tagged envelope. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006693"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"10004","DOI":"10.1128\/JVI.01151-10","article-title":"Interplay of acute and persistent infections caused by Venezuelan equine encephalitis virus encoding mutated capsid protein","volume":"84","author":"Atasheva","year":"2010","journal-title":"J. Virol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1089\/vbz.2014.1717","article-title":"Detection and isolation of Sindbis virus from mosquitoes captured during an outbreak in Sweden, 2013","volume":"15","author":"Bergqvist","year":"2015","journal-title":"Vector Borne Zoonotic Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/1743-422X-3-27","article-title":"Inhibition of histone deacetylation in 293GPG packaging cell line improves the production of self-inactivating MLV-derived retroviral vectors","volume":"3","author":"Jaalouk","year":"2006","journal-title":"Virol. J."},{"key":"ref_57","first-page":"94","article-title":"The physico-chemical factors that govern retrovirus-mediated gene transfer","volume":"25","author":"Palsson","year":"1997","journal-title":"Exp. Hematol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.ymeth.2016.09.016","article-title":"TrackMate: An open and extensible platform for single-particle tracking","volume":"115","author":"Tinevez","year":"2017","journal-title":"Methods"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1016\/j.bpj.2018.01.012","article-title":"Multistep track segmentation and motion classification for transient mobility analysis","volume":"114","author":"Vega","year":"2018","journal-title":"Biophys. J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s00430-020-00675-1","article-title":"Single-nucleotide variants in human CD81 influence hepatitis C virus infection of hepatoma cells","volume":"209","author":"Alberione","year":"2020","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/nri1111","article-title":"The TIM gene family: Emerging roles in immunity and disease","volume":"3","author":"Kuchroo","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.immuni.2007.01.014","article-title":"Structures of T Cell immunoglobulin mucin receptors 1 and 2 reveal mechanisms for regulation of immune responses by the TIM receptor family","volume":"26","author":"Santiago","year":"2007","journal-title":"Immunity"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.4049\/jimmunol.0902937","article-title":"T cell Ig and mucin domain proteins and immunity","volume":"184","author":"Kane","year":"2010","journal-title":"J. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5369","DOI":"10.3748\/wjg.v18.i38.5369","article-title":"Axl glycosylation mediates tumor cell proliferation, invasion and lymphatic metastasis in murine hepatocellular carcinoma","volume":"18","author":"Li","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s12964-019-0377-8","article-title":"Targeting of the AXL receptor tyrosine kinase by small molecule inhibitor leads to AXL cell surface accumulation by impairing the ubiquitin-dependent receptor degradation","volume":"17","author":"Lauter","year":"2019","journal-title":"Cell Commun. Signal."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.virol.2011.04.002","article-title":"Tyrosine kinase receptor Axl enhances entry of Zaire ebolavirus without direct interactions with the viral glycoprotein","volume":"415","author":"Brindley","year":"2011","journal-title":"Virology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1128\/JVI.01278-09","article-title":"The Tyro3 receptor kinase Axl enhances macropinocytosis of Zaire ebolavirus","volume":"85","author":"Hunt","year":"2011","journal-title":"J. Virol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Zapatero-Belinch\u00f3n, F.J., Dietzel, E., Dolnik, O., D\u00f6hner, K., Costa, R., Hertel, B., Veselkova, B., Kirui, J., Klintworth, A., and Manns, M.P. (2019). Characterization of the Filovirus-Resistant Cell Line SH-SY5Y Reveals Redundant Role of Cell Surface Entry Factors. Viruses, 11.","DOI":"10.3390\/v11030275"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1093\/genetics\/55.3.513","article-title":"Genetics of somatic mammalian cells. IV. Properties of Chinese hamster cell mutants with respect to the requirement for proline","volume":"55","author":"Kao","year":"1967","journal-title":"Genetics"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3197","DOI":"10.1073\/pnas.82.10.3197","article-title":"Animal cell mutants defective in glycosaminoglycan biosynthesis","volume":"82","author":"Esko","year":"1985","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"6084","DOI":"10.1128\/JVI.06449-11","article-title":"Attenuation of Chikungunya virus vaccine strain 181\/clone 25 is determined by two amino acid substitutions in the E2 envelope glycoprotein","volume":"86","author":"Gorchakov","year":"2012","journal-title":"J. Virol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3327","DOI":"10.1073\/pnas.75.7.3327","article-title":"Fluorescence probe measurement of the intralysosomal pH in living cells and the perturbation of pH by various agents","volume":"75","author":"Ohkuma","year":"1978","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1083\/jcb.90.3.656","article-title":"Cytoplasmic vacuolation of mouse peritoneal macrophages and the uptake into lysosomes of weakly basic substances","volume":"90","author":"Ohkuma","year":"1981","journal-title":"J. Cell Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e01613","DOI":"10.1128\/JVI.01613-17","article-title":"Axl can serve as entry factor for lassa virus depending on the functional glycosylation of dystroglycan","volume":"92","author":"Fedeli","year":"2018","journal-title":"J. Virol."},{"key":"ref_76","first-page":"83","article-title":"A fatal case of chikungunya virus infection with liver involvement","volume":"65","author":"Chua","year":"2010","journal-title":"Med. J. Malays."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Matusali, G., Colavita, F., Bordi, L., Lalle, E., Ippolito, G., Capobianchi, M.R., and Castilletti, C. (2019). Tropism of the chikungunya virus. Viruses, 11.","DOI":"10.3390\/v11020175"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.chom.2013.07.005","article-title":"Enveloped viruses disable innate immune responses in dendritic cells by direct activation of TAM receptors","volume":"14","author":"Bhattacharyya","year":"2013","journal-title":"Cell Host Microbe"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.chom.2011.03.012","article-title":"The soluble serum protein Gas6 bridges virion envelope phosphatidylserine to the TAM receptor tyrosine kinase Axl to mediate viral entry","volume":"9","author":"Morizono","year":"2011","journal-title":"Cell Host Microbe"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4275","DOI":"10.1128\/JVI.03287-13","article-title":"Role of phosphatidylserine receptors in enveloped virus infection","volume":"88","author":"Morizono","year":"2014","journal-title":"J. Virol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1111\/j.0105-2896.2010.00903.x","article-title":"TIM genes: A family of cell surface phosphatidylserine receptors that regulate innate and adaptive immunity","volume":"235","author":"Freeman","year":"2010","journal-title":"Immunol. Rev."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1007\/s007050050233","article-title":"Early interactions of hepatitis A virus with cultured cells: Viral elution and the effect of pH and calcium ions","volume":"142","author":"Bishop","year":"1997","journal-title":"Arch. Virol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"8426","DOI":"10.1073\/pnas.1019030108","article-title":"T-cell immunoglobulin and mucin domain 1 (TIM-1) is a receptor for Zaire Ebolavirus and Lake Victoria Marburgvirus","volume":"108","author":"Kondratowicz","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1007\/s13238-015-0220-y","article-title":"TIM-1 acts a dual-attachment receptor for ebolavirus by interacting directly with viral GP and the PS on the viral envelope","volume":"6","author":"Yuan","year":"2015","journal-title":"Protein Cell"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.virol.2021.04.013","article-title":"Development of a blocker of the universal phosphatidylserine- and phosphatidylethanolamine-dependent viral entry pathways","volume":"560","author":"Song","year":"2021","journal-title":"Virology"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1093\/emboj\/19.2.187","article-title":"Monoubiquitin carries a novel internalization signal that is appended to activated receptors","volume":"19","author":"Shih","year":"2000","journal-title":"EMBO J."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Lee, C.H.R., Mohamed Hussain, K., and Chu, J.J.H. (2019). Macropinocytosis dependent entry of Chikungunya virus into human muscle cells. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007610"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1042\/bst0120981","article-title":"Semliki forest virus entry and the endocytic pathway","volume":"12","author":"Marsh","year":"1984","journal-title":"Biochem. Soc. Trans."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"796","DOI":"10.3390\/v2040796","article-title":"Alphavirus Entry and Membrane Fusion","volume":"2","author":"Kielian","year":"2010","journal-title":"Viruses"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"733","DOI":"10.20506\/rst.10.3.570","article-title":"Virus survival in the environment","volume":"10","author":"Pirtle","year":"1991","journal-title":"Rev. Sci. Tech."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"E3699","DOI":"10.1073\/pnas.1404851111","article-title":"TIM-family proteins inhibit HIV-1 release","volume":"111","author":"Li","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Amitai, A., Chakraborty, A.K., and Kardar, M. (2018). The low spike density of HIV may have evolved because of the effects of T helper cell depletion on affinity maturation. PLoS Comput. Biol., 14.","DOI":"10.1371\/journal.pcbi.1006408"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.virol.2014.11.013","article-title":"Human keratinocytes restrict chikungunya virus replication at a post-fusion step","volume":"476","author":"Bernard","year":"2015","journal-title":"Virology"},{"key":"ref_94","first-page":"e01583","article-title":"TIM-1 Promotes Hepatitis C Virus Cell Attachment and Infection","volume":"91","author":"Wang","year":"2017","journal-title":"J. Virol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"39739","DOI":"10.1074\/jbc.M200562200","article-title":"Shedding of kidney injury molecule-1, a putative adhesion protein involved in renal regeneration","volume":"277","author":"Bailly","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.2741\/4455","article-title":"Glycosaminoglycans and infection","volume":"21","author":"Aquino","year":"2016","journal-title":"Front. Biosci. (Landmark Ed.)"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/s41564-017-0092-4","article-title":"AXL promotes Zika virus infection in astrocytes by antagonizing type I interferon signalling","volume":"3","author":"Chen","year":"2018","journal-title":"Nat. Microbiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.celrep.2016.12.045","article-title":"Axl mediates ZIKA virus entry in human glial cells and modulates innate immune responses","volume":"18","author":"Meertens","year":"2017","journal-title":"Cell Rep."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/sj.emboj.7600912","article-title":"Structural basis for Gas6-Axl signalling","volume":"25","author":"Sasaki","year":"2006","journal-title":"EMBO J."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1099\/jgv.0.000886","article-title":"Axl is not an indispensable factor for Zika virus infection in mice","volume":"98","author":"Wang","year":"2017","journal-title":"J. Gen. Virol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e01372","DOI":"10.1128\/mBio.01372-19","article-title":"Axl promotes zika virus entry and modulates the antiviral state of human sertoli cells","volume":"10","author":"Strange","year":"2019","journal-title":"MBio"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.antiviral.2010.10.009","article-title":"Cellular IMPDH enzyme activity is a potential target for the inhibition of Chikungunya virus replication and virus induced apoptosis in cultured mammalian cells","volume":"89","author":"Khan","year":"2011","journal-title":"Antivir. Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"3558","DOI":"10.1128\/JVI.02827-15","article-title":"Venezuelan Equine Encephalitis Virus Induces Apoptosis through the Unfolded Protein Response Activation of EGR1","volume":"90","author":"Baer","year":"2016","journal-title":"J. Virol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.virusres.2011.12.009","article-title":"Characterization of Chikungunya virus infection in human neuroblastoma SH-SY5Y cells: Role of apoptosis in neuronal cell death","volume":"163","author":"Dhanwani","year":"2012","journal-title":"Virus Res."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Nayak, T.K., Mamidi, P., Kumar, A., Singh, L.P.K., Sahoo, S.S., Chattopadhyay, S., and Chattopadhyay, S. (2017). Regulation of Viral Replication, Apoptosis and Pro-Inflammatory Responses by 17-AAG during Chikungunya Virus Infection in Macrophages. Viruses, 9.","DOI":"10.3390\/v9010003"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1096\/fj.10-164178","article-title":"Chikungunya virus mobilizes the apoptotic machinery to invade host cell defenses","volume":"25","author":"Denizot","year":"2011","journal-title":"FASEB J."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S1473-3099(07)70107-X","article-title":"Chikungunya, an epidemic arbovirosis","volume":"7","author":"Pialoux","year":"2007","journal-title":"Lancet Infect. Dis."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/ni1185","article-title":"TIM-4 is the ligand for TIM-1, and the TIM-1-TIM-4 interaction regulates T cell proliferation","volume":"6","author":"Meyers","year":"2005","journal-title":"Nat. Immunol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/ni1186","article-title":"TIM-1 induces T cell activation and inhibits the development of peripheral tolerance","volume":"6","author":"Umetsu","year":"2005","journal-title":"Nat. Immunol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/7\/1828\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:32:09Z","timestamp":1760164329000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/7\/1828"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,20]]},"references-count":109,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["cells10071828"],"URL":"https:\/\/doi.org\/10.3390\/cells10071828","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,20]]}}}