{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T02:04:53Z","timestamp":1779329093518,"version":"3.51.4"},"reference-count":118,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T00:00:00Z","timestamp":1669075200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Maine IDeA Network of Biomedical Research Excellence (INBRE)","award":["P20GM103423"],"award-info":[{"award-number":["P20GM103423"]}]},{"name":"the Maine IDeA Network of Biomedical Research Excellence (INBRE)","award":["R15AI144686"],"award-info":[{"award-number":["R15AI144686"]}]},{"name":"the Maine IDeA Network of Biomedical Research Excellence (INBRE)","award":["R15GM116002"],"award-info":[{"award-number":["R15GM116002"]}]},{"name":"the Maine IDeA Network of Biomedical Research Excellence (INBRE)","award":["R15GM139070"],"award-info":[{"award-number":["R15GM139070"]}]},{"name":"the National Institute of Allergy and Infectious Diseases","award":["P20GM103423"],"award-info":[{"award-number":["P20GM103423"]}]},{"name":"the National Institute of Allergy and Infectious Diseases","award":["R15AI144686"],"award-info":[{"award-number":["R15AI144686"]}]},{"name":"the National Institute of Allergy and Infectious Diseases","award":["R15GM116002"],"award-info":[{"award-number":["R15GM116002"]}]},{"name":"the National Institute of Allergy and Infectious Diseases","award":["R15GM139070"],"award-info":[{"award-number":["R15GM139070"]}]},{"name":"National Institute of General Medical Sciences","award":["P20GM103423"],"award-info":[{"award-number":["P20GM103423"]}]},{"name":"National Institute of General Medical Sciences","award":["R15AI144686"],"award-info":[{"award-number":["R15AI144686"]}]},{"name":"National Institute of General Medical Sciences","award":["R15GM116002"],"award-info":[{"award-number":["R15GM116002"]}]},{"name":"National Institute of General Medical Sciences","award":["R15GM139070"],"award-info":[{"award-number":["R15GM139070"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The organization and dynamics of plasma membrane receptors are a critical link in virus-receptor interactions, which finetune signaling efficiency and determine cellular responses during infection. Characterizing the mechanisms responsible for the active rearrangement and clustering of receptors may aid in developing novel strategies for the therapeutic treatment of viruses. Virus-receptor interactions are poorly understood at the nanoscale, yet they present an attractive target for the design of drugs and for the illumination of viral infection and pathogenesis. This study utilizes super-resolution microscopy and related techniques, which surpass traditional microscopy resolution limitations, to provide both a spatial and temporal assessment of the interactions of human JC polyomavirus (JCPyV) with 5-hydroxytrypamine 2 receptors (5-HT2Rs) subtypes during viral entry. JCPyV causes asymptomatic kidney infection in the majority of the population and can cause fatal brain disease, and progressive multifocal leukoencephalopathy (PML), in immunocompromised individuals. Using Fluorescence Photoactivation Localization Microscopy (FPALM), the colocalization of JCPyV with 5-HT2 receptor subtypes (5-HT2A, 5-HT2B, and 5-HT2C) during viral attachment and viral entry was analyzed. JCPyV was found to significantly enhance the clustering of 5-HT2 receptors during entry. Cluster analysis of infected cells reveals changes in 5-HT2 receptor cluster attributes, and radial distribution function (RDF) analyses suggest a significant increase in the aggregation of JCPyV particles colocalized with 5-HT2 receptor clusters in JCPyV-infected samples. These findings provide novel insights into receptor patterning during viral entry and highlight improved technologies for the future development of therapies for JCPyV infection as well as therapies for diseases involving 5-HT2 receptors.<\/jats:p>","DOI":"10.3390\/v14122597","type":"journal-article","created":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T02:55:51Z","timestamp":1669172151000},"page":"2597","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Dynamics and Patterning of 5-Hydroxytryptamine 2 Subtype Receptors in JC Polyomavirus Entry"],"prefix":"10.3390","volume":"14","author":[{"given":"Kashif","family":"Mehmood","sequence":"first","affiliation":[{"name":"Department of Molecular and Biomedical Sciences, The University of Maine, Orono, ME 04469, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael P.","family":"Wilczek","sequence":"additional","affiliation":[{"name":"Department of Molecular and Biomedical Sciences, The University of Maine, Orono, ME 04469, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeanne K.","family":"DuShane","sequence":"additional","affiliation":[{"name":"Department of Molecular and Biomedical Sciences, The University of Maine, Orono, ME 04469, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3346-1271","authenticated-orcid":false,"given":"Matthew T.","family":"Parent","sequence":"additional","affiliation":[{"name":"Department of Physics & Astronomy, The University of Maine, Orono, ME 04469, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colleen L.","family":"Mayberry","sequence":"additional","affiliation":[{"name":"Department of Molecular and Biomedical Sciences, The University of Maine, Orono, ME 04469, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5150-9390","authenticated-orcid":false,"given":"Jaqulin N.","family":"Wallace","sequence":"additional","affiliation":[{"name":"Department of Physics & Astronomy, The University of Maine, Orono, ME 04469, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francois L.","family":"Levasseur","sequence":"additional","affiliation":[{"name":"Department of Molecular and Biomedical Sciences, The University of Maine, Orono, ME 04469, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tristan M.","family":"Fong","sequence":"additional","affiliation":[{"name":"Department of Molecular and Biomedical Sciences, The University of Maine, Orono, ME 04469, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel T.","family":"Hess","sequence":"additional","affiliation":[{"name":"Department of Physics & Astronomy, The University of Maine, Orono, ME 04469, USA"},{"name":"Graduate School of Biomedical Science and Engineering, The University of Maine, Orono, ME 04469, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa S.","family":"Maginnis","sequence":"additional","affiliation":[{"name":"Department of Molecular and Biomedical Sciences, The University of Maine, Orono, ME 04469, USA"},{"name":"Graduate School of Biomedical Science and Engineering, The University of Maine, Orono, ME 04469, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.ceb.2011.05.003","article-title":"Signaling clusters in the cell membrane","volume":"23","author":"Hartman","year":"2011","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2794","DOI":"10.3390\/v7062747","article-title":"Dynamics of virus-receptor interactions in virus binding, signaling, and endocytosis","volume":"7","author":"Boulant","year":"2015","journal-title":"Viruses"},{"key":"ref_3","first-page":"3533","article-title":"Outside-in signaling\u2014A brief review of GPCR signaling with a focus on the Drosophila GPCR family","volume":"128","author":"Hanlon","year":"2015","journal-title":"J. Cell Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1083\/jcb.200211018","article-title":"Anthrax toxin triggers endocytosis of its receptor via a lipid raft-mediated clathrin-dependent process","volume":"160","author":"Abrami","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Eierhoff, T., Hrincius, E.R., Rescher, U., Ludwig, S., and Ehrhardt, C. (2010). The epidermal growth factor receptor (EGFR) promotes uptake of influenza A viruses (IAV) into host cells. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1001099"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.coemr.2020.07.003","article-title":"Spatiotemporal control of GLP-1 receptor activity","volume":"16","author":"Manchanda","year":"2021","journal-title":"Curr. Opin. Endocr. Metab. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"iv","DOI":"10.1016\/j.coemr.2021.02.001","article-title":"Editorial: G protein\u2013coupled receptors: From molecules to medicine","volume":"16","author":"Hanyaloglu","year":"2021","journal-title":"Curr. Opin. Endocr. Metab. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/nrc3277","article-title":"Spatial regulation of receptor tyrosine kinases in development and cancer","volume":"12","author":"Casaletto","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"011021","DOI":"10.1117\/1.JBO.19.1.011021","article-title":"Spatial cluster analysis of nanoscopically mapped serotonin receptors for classification of fixed brain tissue","volume":"19","author":"Sams","year":"2014","journal-title":"J. Biomed. Opt."},{"key":"ref_10","unstructured":"Tiberi, M. (2019). Super-Resolution Imaging of G Protein-Coupled Receptors Using Ground State Depletion Microscopy. G Protein-Coupled Receptor Signaling: Methods and Protocols, Springer."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4258","DOI":"10.1529\/biophysj.106.091116","article-title":"Ultra-high resolution imaging by fluorescence photoactivation localization microscopy","volume":"91","author":"Hess","year":"2006","journal-title":"Biophys. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/nmeth929","article-title":"Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM)","volume":"3","author":"Rust","year":"2006","journal-title":"Nat. Methods"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1126\/science.1127344","article-title":"Imaging intracellular fluorescent proteins at nanometer resolution","volume":"313","author":"Betzig","year":"2006","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.3390\/v6031365","article-title":"Super-resolution microscopy: A virus\u2019 eye view of the cell","volume":"6","author":"Grove","year":"2014","journal-title":"Viruses"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1126\/science.1226359","article-title":"Maturation-dependent HIV-1 surface protein redistribution revealed by fluorescence nanoscopy","volume":"338","author":"Chojnacki","year":"2012","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Muranyi, W., Malkusch, S., Muller, B., Heilemann, M., and Krausslich, H.G. (2013). Super-resolution microscopy reveals specific recruitment of HIV-1 envelope proteins to viral assembly sites dependent on the envelope C-terminal tail. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003198"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"11815","DOI":"10.1128\/JVI.01022-12","article-title":"Flavivirus replication complex assembly revealed by DNAJC14 functional mapping","volume":"86","author":"Yi","year":"2012","journal-title":"J. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"He, J., Sun, E., Bujny, M.V., Kim, D., Davidson, M.W., and Zhuang, X. (2013). Dual function of CD81 in influenza virus uncoating and budding. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003701"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Eggert, D., Rosch, K., Reimer, R., and Herker, E. (2014). Visualization and analysis of hepatitis C virus structural proteins at lipid droplets by super-resolution microscopy. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0102511"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.chom.2013.09.004","article-title":"Tracking viral genomes in host cells at single-molecule resolution","volume":"14","author":"Wang","year":"2013","journal-title":"Cell Host Microbe"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"29132","DOI":"10.1038\/srep29132","article-title":"VirusMapper: Open-source nanoscale mapping of viral architecture through super-resolution microscopy","volume":"6","author":"Gray","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"20937","DOI":"10.1038\/s41598-020-77170-3","article-title":"Super resolution microscopy and deep learning identify Zika virus reorganization of the endoplasmic reticulum","volume":"10","author":"Long","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/nprot.2008.246","article-title":"Imaging biological structures with fluorescence photoactivation localization microscopy","volume":"4","author":"Gould","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/bs.ctm.2015.03.008","article-title":"Dances with Membranes: Breakthroughs from Super-resolution Imaging","volume":"75","author":"Curthoys","year":"2015","journal-title":"Curr. Top Membr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/j.bpj.2019.01.017","article-title":"Influenza Hemagglutinin Modulates Phosphatidylinositol 4,5-Bisphosphate Membrane Clustering","volume":"116","author":"Curthoys","year":"2019","journal-title":"Biophys. J."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Hawkes, P.W., and Spence, J.C.H. (2019). Fluorescence Microscopy with Nanometer Resolution. Springer Handbook of Microscopy, Spinger.","DOI":"10.1007\/978-3-030-00069-1"},{"key":"ref_27","first-page":"93","article-title":"Progressive multifocal leuko-encephalopathy; a hitherto unrecognized complication of chronic lymphatic leukaemia and Hodgkin\u2019s disease","volume":"81","author":"Astrom","year":"1958","journal-title":"Brain"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1055\/s-2008-1040837","article-title":"Progressive multifocal leukoencephalopathy","volume":"19","author":"Berger","year":"1999","journal-title":"Semin. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.jneuroim.2010.09.021","article-title":"Progressive multifocal leukoencephalopathy","volume":"231","author":"Weissert","year":"2011","journal-title":"J. Neuroimmunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/0928-0197(95)00012-W","article-title":"The JC virus antibody response in serum and cerebrospinal fluid in progressive multifocal leucoencephalopathy","volume":"4","author":"Knowles","year":"1995","journal-title":"Clin. Diagn. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1099\/vir.0.18842-0","article-title":"Seroepidemiology of the human polyomaviruses","volume":"84","author":"Stolt","year":"2003","journal-title":"J. Gen. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1086\/597126","article-title":"Prevalence of polyomavirus BK and JC infection and replication in 400 healthy blood donors","volume":"199","author":"Egli","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kean, J.M., Rao, S., Wang, M., and Garcea, R.L. (2009). Seroepidemiology of human polyomaviruses. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000363"},{"key":"ref_34","first-page":"5","article-title":"JC virus: A brief review","volume":"3","author":"Palacio","year":"2013","journal-title":"World J. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1002\/(SICI)1096-9071(199803)54:3<196::AID-JMV10>3.0.CO;2-G","article-title":"Nucleic acid detection as a diagnostic tool in polyomavirus JC induced progressive multifocal leukoencephalopathy","volume":"54","author":"Dorries","year":"1998","journal-title":"J. Med. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3139","DOI":"10.1128\/jvi.64.6.3139-3143.1990","article-title":"Isolation of a possible archetypal JC virus DNA sequence from nonimmunocompromised individuals","volume":"64","author":"Yogo","year":"1990","journal-title":"J. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Atkinson, A.L., and Atwood, W.J. (2020). Fifty Years of JC Polyomavirus: A Brief Overview and Remaining Questions. Viruses, 12.","DOI":"10.3390\/v12090969"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1126\/science.148.3676.1477","article-title":"Particles Resembling Papova Viruses in Human Cerebral Demyelinating Disease","volume":"148","author":"Zurhein","year":"1965","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/BF00686519","article-title":"Electron microscopic observations on a case of progressive multifocal leukoencephalopathy","volume":"5","author":"Silverman","year":"1965","journal-title":"Acta Neuropathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1128\/CMR.05031-11","article-title":"Molecular biology, epidemiology, and pathogenesis of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain","volume":"25","author":"Ferenczy","year":"2012","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1007\/s00415-016-8217-x","article-title":"Drug-associated progressive multifocal leukoencephalopathy: A clinical, radiological, and cerebrospinal fluid analysis of 326 cases","volume":"263","author":"Maas","year":"2016","journal-title":"J. Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1056\/NEJMoa051782","article-title":"Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis","volume":"353","author":"Tyler","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/S1470-2045(09)70161-5","article-title":"Monoclonal antibody-associated progressive multifocal leucoencephalopathy in patients treated with rituximab, natalizumab, and efalizumab: A Review from the Research on Adverse Drug Events and Reports (RADAR) Project","volume":"10","author":"Carson","year":"2009","journal-title":"Lancet Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1146\/annurev.med.080708.082655","article-title":"Progressive multifocal leukoencephalopathy in patients on immunomodulatory therapies","volume":"61","author":"Major","year":"2010","journal-title":"Annu. Rev. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1056\/NEJMoa1107829","article-title":"Risk of natalizumab-associated progressive multifocal leukoencephalopathy","volume":"366","author":"Bloomgren","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4404","DOI":"10.1128\/JVI.02657-08","article-title":"JC virus-specific immune responses in human immunodeficiency virus type 1 patients with progressive multifocal leukoencephalopathy","volume":"83","author":"Khanna","year":"2009","journal-title":"J. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/s41582-020-00427-y","article-title":"Progressive multifocal leukoencephalopathy and the spectrum of JC virus-related disease","volume":"17","author":"Cortese","year":"2021","journal-title":"Nat. Rev. Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1007\/s13365-015-0316-4","article-title":"Predictors of survival and functional outcomes in natalizumab-associated progressive multifocal leukoencephalopathy","volume":"21","author":"Gheuens","year":"2015","journal-title":"J. NeuroVirology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1177\/1756285615602832","article-title":"Progressive multifocal leukoencephalopathy: Current treatment options and future perspectives","volume":"8","author":"Pavlovic","year":"2015","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"ref_50","first-page":"109","article-title":"Progressive Multifocal Leukoencephalopathy: Current Insights","volume":"9","author":"Kartau","year":"2019","journal-title":"Degener. Neurol. Neuromuscul. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1111\/apm.12128","article-title":"The human JC polyomavirus (JCPyV): Virological background and clinical implications","volume":"121","author":"Hirsch","year":"2013","journal-title":"Apmis"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/nrneurol.2010.164","article-title":"Progressive multifocal leukoencephalopathy and other forms of JC virus disease","volume":"6","author":"Brew","year":"2010","journal-title":"Nat. Rev. Neurol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/S1474-4422(10)70028-4","article-title":"Natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: Lessons from 28 cases","volume":"9","author":"Clifford","year":"2010","journal-title":"Lancet Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1007\/s11910-012-0313-4","article-title":"Update on progressive multifocal leukoencephalopathy","volume":"12","author":"Steiner","year":"2012","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1212\/01.wnl.0000343510.08643.74","article-title":"PML-IRIS in patients with HIV infection: Clinical manifestations and treatment with steroids","volume":"72","author":"Tan","year":"2009","journal-title":"Neurology"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"DuShane, J.K., and Maginnis, M.S. (2019). Human DNA Virus Exploitation of the MAPK-ERK Cascade. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20143427"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1007\/s13365-014-0272-4","article-title":"JC polyomavirus attachment, entry, and trafficking: Unlocking the keys to a fatal infection","volume":"21","author":"Maginnis","year":"2015","journal-title":"J. Neurovirol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1515\/hsz-2016-0345","article-title":"The biology of JC polyomavirus","volume":"398","author":"Assetta","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3233","DOI":"10.1093\/emboj\/17.12.3233","article-title":"Interaction of polyomavirus internal protein VP2 with the major capsid protein VP1 and implications for participation of VP2 in viral entry","volume":"17","author":"Chen","year":"1998","journal-title":"EMBO J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e00379-19","DOI":"10.1128\/mBio.00379-19","article-title":"JC Polyomavirus Uses Extracellular Vesicles To Infect Target Cells","volume":"10","author":"Gee","year":"2019","journal-title":"mBio"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.chom.2010.09.004","article-title":"Structure-function analysis of the human JC polyomavirus establishes the LSTc pentasaccharide as a functional receptor motif","volume":"8","author":"Neu","year":"2010","journal-title":"Cell Host Microbe"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e00247-13","DOI":"10.1128\/mBio.00247-13","article-title":"Progressive multifocal leukoencephalopathy-associated mutations in the JC polyomavirus capsid disrupt lactoseries tetrasaccharide c binding","volume":"4","author":"Maginnis","year":"2013","journal-title":"mBio"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"6364","DOI":"10.1128\/JVI.00489-15","article-title":"The Greater Affinity of JC Polyomavirus Capsid for alpha2,6-Linked Lactoseries Tetrasaccharide c than for Other Sialylated Glycans Is a Major Determinant of Infectivity","volume":"89","author":"Stroh","year":"2015","journal-title":"J. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/j.celrep.2017.10.027","article-title":"Infectious Entry and Neutralization of Pathogenic JC Polyomaviruses","volume":"21","author":"Geoghegan","year":"2017","journal-title":"Cell Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1126\/science.1103492","article-title":"The human polyomavirus, JCV, uses serotonin receptors to infect cells","volume":"306","author":"Elphick","year":"2004","journal-title":"Science"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"13490","DOI":"10.1128\/JVI.02252-13","article-title":"5-HT2 receptors facilitate JC polyomavirus entry","volume":"87","author":"Assetta","year":"2013","journal-title":"J. Virol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e01948-18","DOI":"10.1128\/JVI.01948-18","article-title":"JC polyomavirus entry by clathrin-mediated endocytosis is driven by \u03b2-arrestin","volume":"93","author":"Mayberry","year":"2019","journal-title":"J. Virol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1016\/j.celrep.2019.04.067","article-title":"Genetic and Functional Dissection of the Role of Individual 5-HT2 Receptors as Entry Receptors for JC Polyomavirus","volume":"27","author":"Assetta","year":"2019","journal-title":"Cell Rep."},{"key":"ref_69","first-page":"230","article-title":"5-Hydroxytryptamine2A receptors expressed in rat renal mesangial cells inhibit cyclic AMP accumulation","volume":"48","author":"Garnovskaya","year":"1995","journal-title":"Mol. Pharmacol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"F1468","DOI":"10.1152\/ajprenal.00246.2007","article-title":"Characterization of a putative intrarenal serotonergic system","volume":"293","author":"Xu","year":"2007","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Jenkins, T.A., Nguyen, J.C., Polglaze, K.E., and Bertrand, P.P. (2016). Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis. Nutrients, 8.","DOI":"10.3390\/nu8010056"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.bbr.2014.07.038","article-title":"The role of serotonin in adult hippocampal neurogenesis","volume":"277","author":"Alenina","year":"2015","journal-title":"Behav. Brain Res."},{"key":"ref_73","first-page":"226","article-title":"Protective Effects of Lithium on Sumatriptan-Induced Memory Impairment in Mice","volume":"54","author":"Nikoui","year":"2016","journal-title":"Acta Med. Iran."},{"key":"ref_74","unstructured":"Squire, L.R. (2009). Serotonin (5-Hydroxytryptamine; 5-HT): Receptors. In Encyclopedia of Neuroscience, Academic Press."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/S0091-3057(01)00746-8","article-title":"Molecular, pharmacological and functional diversity of 5-HT receptors","volume":"71","author":"Hoyer","year":"2002","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4619","DOI":"10.1091\/mbc.e06-03-0218","article-title":"Opposite effects of PSD-95 and MPP3 PDZ proteins on serotonin 5-hydroxytryptamine2C receptor desensitization and membrane stability","volume":"17","author":"Gavarini","year":"2006","journal-title":"Mol. Biol. Cell"},{"key":"ref_77","first-page":"306","article-title":"Rapid agonist-induced internalization of the 5-hydroxytryptamine2A receptor occurs via the endosome pathway in vitro","volume":"50","author":"Berry","year":"1996","journal-title":"Mol. Pharmacol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"ra16","DOI":"10.1126\/scisignal.aac9177","article-title":"Plasma membrane localization of the mu-opioid receptor controls spatiotemporal signaling","volume":"9","author":"Halls","year":"2016","journal-title":"Sci. Signal"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"eaao1917","DOI":"10.1126\/scisignal.aao1917","article-title":"Single-molecule diffusion-based estimation of ligand effects on G protein-coupled receptors","volume":"11","author":"Yanagawa","year":"2018","journal-title":"Sci. Signal"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/tra.12628","article-title":"Regulation of G protein-coupled receptor signaling by plasma membrane organization and endocytosis","volume":"20","author":"Weinberg","year":"2019","journal-title":"Traffic"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.jad.2014.03.011","article-title":"Serotonin 2A receptor clustering in peripheral lymphocytes is altered in major depression and may be a biomarker of therapeutic efficacy","volume":"163","author":"Olivares","year":"2014","journal-title":"J. Affect. Disord."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"4075","DOI":"10.1038\/s41467-019-11875-6","article-title":"Exploring use of unsupervised clustering to associate signaling profiles of GPCR ligands to clinical response","volume":"10","author":"Benredjem","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1097\/00005072-198907000-00004","article-title":"Human fetal astrocytes in culture support the growth of the neurotropic human polyomavirus, JCV","volume":"48","author":"Major","year":"1989","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/0042-6822(89)90425-X","article-title":"Extension of JC virus host range to monkey cells by insertion of a simian virus 40 enhancer into the JC virus regulatory region","volume":"170","author":"Vacante","year":"1989","journal-title":"Virology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e00729-13","DOI":"10.1128\/mBio.00729-13","article-title":"A Retrograde Trafficking Inhibitor of Ricin and Shiga-Like Toxins Inhibits Infection of Cells by Human and Monkey Polyomaviruses","volume":"4","author":"Nelson","year":"2013","journal-title":"mBio"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2182","DOI":"10.1016\/j.bpj.2013.03.054","article-title":"Actin mediates the nanoscale membrane organization of the clustered membrane protein influenza hemagglutinin","volume":"104","author":"Gudheti","year":"2013","journal-title":"Biophys. J."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e01529-17","DOI":"10.1128\/JVI.01529-17","article-title":"ERK Is a Critical Regulator of JC Polyomavirus Infection","volume":"92","author":"DuShane","year":"2018","journal-title":"J. Virol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e00174-20","DOI":"10.1128\/JVI.00174-20","article-title":"Correction for Wilczek et al. \u201cJC Polyomavirus Infection Reveals Delayed Progression of the Infectious Cycle in Normal Human Astrocytes\u201d","volume":"94","author":"Wilczek","year":"2020","journal-title":"J. Virol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"9677","DOI":"10.1128\/JVI.00978-10","article-title":"Role of N-linked glycosylation of the 5-HT2A receptor in JC virus infection","volume":"84","author":"Maginnis","year":"2010","journal-title":"J. Virol."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Wickham, H. (2016). ggplot2: Elegant Graphics for Data Analysis. Use R!, Springer. [2nd ed.].","DOI":"10.1007\/978-3-319-24277-4_9"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_92","first-page":"e50680","article-title":"Simultaneous multicolor imaging of biological structures with fluorescence photoactivation localization microscopy","volume":"82","author":"Curthoys","year":"2013","journal-title":"J. Vis. Exp."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1016\/j.bpj.2011.07.049","article-title":"Superresolution imaging of multiple fluorescent proteins with highly overlapping emission spectra in living cells","volume":"101","author":"Gunewardene","year":"2011","journal-title":"Biophys. J."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/nprot.2011.336","article-title":"Direct stochastic optical reconstruction microscopy with standard fluorescent probes","volume":"6","author":"Loschberger","year":"2011","journal-title":"Nat. Protoc."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3854","DOI":"10.1038\/srep03854","article-title":"The fidelity of stochastic single-molecule super-resolution reconstructions critically depends upon robust background estimation","volume":"4","author":"Hoogendoorn","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/nbt1191","article-title":"Engineering of a monomeric green-to-red photoactivatable fluorescent protein induced by blue light","volume":"24","author":"Gurskaya","year":"2006","journal-title":"Nat. Biotechnol."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Chen, J., Almo, S.C., and Wu, Y. (2017). General principles of binding between cell surface receptors and multi-specific ligands: A computational study. PLoS Comput. Biol., 13.","DOI":"10.1371\/journal.pcbi.1005805"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1128\/JVI.01534-06","article-title":"The Level of CD81 Cell Surface Expression Is a Key Determinant for Productive Entry of Hepatitis C Virus into Host Cells","volume":"81","author":"Koutsoudakis","year":"2007","journal-title":"J. Virol."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Franke, C., Chum, T., Kv\u00ed\u010dalov\u00e1, Z., Glatzov\u00e1, D., Rodriguez, A., Helmerich, D.A., Frank, O., Brdi\u010dka, T., van de Linde, S., and Cebecauer, M. (2020). Unraveling nanotopography of cell surface receptors. bioRxiv.","DOI":"10.1101\/2019.12.23.884460"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Neu, U., Allen, S.A., Blaum, B.S., Liu, Y., Frank, M., Palma, A.S., Stroh, L.J., Feizi, T., Peters, T., and Atwood, W.J. (2013). A structure-guided mutation in the major capsid protein retargets BK polyomavirus. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003688"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Handala, L., Fiore, T., Rouille, Y., and Helle, F. (2019). QuantIF: An ImageJ Macro to Automatically Determine the Percentage of Infected Cells after Immunofluorescence. Viruses, 11.","DOI":"10.3390\/v11020165"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"28940","DOI":"10.1038\/srep28940","article-title":"Cargo binding promotes KDEL receptor clustering at the mammalian cell surface","volume":"6","author":"Becker","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_103","unstructured":"Parent, M. (2020). Quantification of Interactions Between Influenza Hemagglutinin and Host Cell Phosphoinositides by Super-Resolution Microscopy, University of Maine."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1080\/08893110500078704","article-title":"X-ray crystallography of virus-receptor complexes: Structure of a minor group rhinovirus bound to its cellular receptor protein","volume":"11","author":"Fita","year":"2005","journal-title":"Crystallogr. Rev."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Sewald, X. (2018). Visualizing Viral Infection In Vivo by Multi-Photon Intravital Microscopy. Viruses, 10.","DOI":"10.3390\/v10060337"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e03100-20","DOI":"10.1128\/mBio.03100-20","article-title":"Direct Intracellular Visualization of Ebola Virus-Receptor Interaction by In Situ Proximity Ligation","volume":"12","author":"Mittler","year":"2021","journal-title":"mBio"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/imr.12010","article-title":"Super-resolution characterization of TCR-dependent signaling clusters","volume":"251","author":"Sherman","year":"2013","journal-title":"Immunol. Rev."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"5494","DOI":"10.1021\/acs.jpcb.9b05176","article-title":"Characterizing Large-Scale Receptor Clustering on the Single Cell Level: A Comparative Plasmon Coupling and Fluorescence Superresolution Microscopy Study","volume":"123","author":"Zhang","year":"2019","journal-title":"J. Phys. Chem. B"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/s41467-018-08064-2","article-title":"TCR microclusters form spatially segregated domains and sequentially assemble in calcium-dependent kinetic steps","volume":"10","author":"Yi","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1128\/JVI.74.5.2288-2292.2000","article-title":"JC virus enters human glial cells by clathrin-dependent receptor-mediated endocytosis","volume":"74","author":"Pho","year":"2000","journal-title":"J. Virol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"14470","DOI":"10.1073\/pnas.212517999","article-title":"Internalization and recycling of 5-HT2A receptors activated by serotonin and protein kinase C-mediated mechanisms","volume":"99","author":"Bhattacharyya","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1016\/j.yexcr.2010.02.034","article-title":"Regulation of serotonin receptor function in the nervous system by lipid rafts and adaptor proteins","volume":"316","author":"Bjork","year":"2010","journal-title":"Exp. Cell Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/j.neuropharm.2008.06.048","article-title":"Insights into the regulation of 5-HT2A serotonin receptors by scaffolding proteins and kinases","volume":"55","author":"Allen","year":"2008","journal-title":"Neuropharmacology"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.bpj.2010.12.3692","article-title":"Organization of higher-order oligomers of the serotonin1A receptor explored utilizing homo-FRET in live cells","volume":"100","author":"Ganguly","year":"2011","journal-title":"Biophys. J."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s00221-013-3622-1","article-title":"Functional significance of serotonin receptor dimerization","volume":"230","year":"2013","journal-title":"Exp. Brain Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1124\/mol.108.054395","article-title":"Evidence for distinct antagonist-revealed functional states of 5-hydroxytryptamine2A receptor homodimers","volume":"75","author":"Brea","year":"2009","journal-title":"Mol. Pharmacol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1016\/j.bbamcr.2010.08.010","article-title":"Hetero-dimerization of serotonin 5-HT2A and dopamine D2 receptors","volume":"1803","author":"Lukasiewicz","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.neuropharm.2011.05.023","article-title":"Functional crosstalk and heteromerization of serotonin 5-HT2A and dopamine D2 receptors","volume":"61","author":"Albizu","year":"2011","journal-title":"Neuropharmacology"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/12\/2597\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:24:34Z","timestamp":1760145874000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/12\/2597"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,22]]},"references-count":118,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["v14122597"],"URL":"https:\/\/doi.org\/10.3390\/v14122597","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,22]]}}}