{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T04:43:21Z","timestamp":1788410601690,"version":"build-2803163510"},"reference-count":144,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T00:00:00Z","timestamp":1628467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["31003A_179256 \/ 1"],"award-info":[{"award-number":["31003A_179256 \/ 1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Cell-to-cell variability of infection has long been known, yet it has remained one of the least understood phenomena in infection research. It impacts on disease onset and development, yet only recently underlying mechanisms have been studied in clonal cell cultures by single-virion immunofluorescence microscopy and flow cytometry. In this review, we showcase how single-cell RNA sequencing (scRNA-seq), single-molecule RNA-fluorescence in situ hybridization (FISH), and copper(I)-catalyzed azide-alkyne cycloaddition (click) with alkynyl-tagged viral genomes dissect infection variability in human and mouse cells. We show how the combined use of scRNA-FISH and click-chemistry reveals highly variable onsets of adenoviral gene expression, and how single live cell plaques reveal lytic and nonlytic adenovirus transmissions. The review highlights how scRNA-seq profiling and scRNA-FISH of coxsackie, influenza, dengue, zika, and herpes simplex virus infections uncover transcriptional variability, and how the host interferon response tunes influenza and sendai virus infections. We introduce the concept of \u201ccell state\u201d in infection variability, and conclude with advances by single-cell simultaneous measurements of chromatin accessibility and mRNA counts at high-throughput. Such technology will further dissect the sequence of events in virus infection and pathology, and better characterize the genetic and genomic stability of viruses, cell autonomous innate immune responses, and mechanisms of tissue injury.<\/jats:p>","DOI":"10.3390\/v13081568","type":"journal-article","created":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T05:17:06Z","timestamp":1628486226000},"page":"1568","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Virus Infection Variability by Single-Cell Profiling"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3276-3008","authenticated-orcid":false,"given":"Maarit","family":"Suomalainen","sequence":"first","affiliation":[{"name":"Department of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urs F.","family":"Greber","sequence":"additional","affiliation":[{"name":"Department of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1073\/pnas.38.8.747","article-title":"Production of Plaques in Monolayer Tissue Cultures by Single Particles of an Animal Virus","volume":"38","author":"Dulbecco","year":"1952","journal-title":"Proc. Natl. Acad Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1093\/embo-reports\/kvf093","article-title":"Signalling takes control of nucleo-cytoplasmic trafficking. Workshop on signal-regulated nuclear transport","volume":"3","author":"Greber","year":"2020","journal-title":"EMBO Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/nrg2583","article-title":"Evolutionary analysis of the dynamics of viral infectious disease","volume":"10","author":"Pybus","year":"2009","journal-title":"Nat. Rev. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"8938","DOI":"10.1038\/ncomms9938","article-title":"Single-cell analysis and stochastic modelling unveil large cell-to-cell variability in influenza A virus infection","volume":"6","author":"Heldt","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1146\/annurev-virology-092818-015550","article-title":"Adenovirus Entry: From Infection to Immunity","volume":"6","author":"Greber","year":"2019","journal-title":"Annu. Rev. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Gelbart, M., Harari, S., Ben-Ari, Y., Kustin, T., Wolf, D., Mandelboim, M., Mor, O., Pennings, P.S., and Stern, A. (2020). Drivers of within-host genetic diversity in acute infections of viruses. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1009029"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.cell.2016.04.019","article-title":"Mass Cytometry: Single Cells, Many Features","volume":"165","author":"Spitzer","year":"2016","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1016\/j.cell.2019.01.020","article-title":"Extensive Heterogeneity and Intrinsic Variation in Spatial Genome Organization","volume":"176","author":"Finn","year":"2019","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-018-0071-8","article-title":"Single-cell RNA sequencing technologies and bioinformatics pipelines","volume":"50","author":"Hwang","year":"2018","journal-title":"Exp. Mol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1146\/annurev-virology-021820-102458","article-title":"Single-Cell Analysis Reveals Heterogeneity of Virus Infection, Pathogenicity, and Host Responses: HIV as a Pioneering Example","volume":"7","author":"Brandt","year":"2020","journal-title":"Annu. Rev. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"10123","DOI":"10.1128\/JVI.01102-12","article-title":"Cell-free transmission of human adenovirus by passive mass transfer in cell culture simulated in a computer model","volume":"86","author":"Yakimovich","year":"2012","journal-title":"J. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Yakimovich, A., Andriasyan, V., Witte, R., Wang, I.H., Prasad, V., Suomalainen, M., and Greber, U.F. (2015). Plaque2.0-A High-Throughput Analysis Framework to Score Virus-Cell Transmission and Clonal Cell Expansion. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0138760"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"13086","DOI":"10.1128\/JVI.02156-14","article-title":"Chemical Induction of Unfolded Protein Response Enhances Cancer Cell Killing through Lytic Virus Infection","volume":"88","author":"Prasad","year":"2014","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e00599-18","DOI":"10.1128\/mSphereDirect.00599-18","article-title":"Label-Free Digital Holo-tomographic Microscopy Reveals Virus-Induced Cytopathic Effects in Live Cells","volume":"3","author":"Yakimovich","year":"2018","journal-title":"mSphere"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s11904-018-0376-1","article-title":"Tools for Visualizing HIV in Cure Research","volume":"15","author":"Niessl","year":"2018","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/j.tim.2017.06.002","article-title":"Unravelling HIV-1 Latency, One Cell at a Time","volume":"25","author":"Kok","year":"2017","journal-title":"Trends Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e00047-19","DOI":"10.1128\/JVI.00047-19","article-title":"The Transcriptome of Latent Human Cytomegalovirus","volume":"93","author":"Schwartz","year":"2019","journal-title":"J. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"lqaa059","DOI":"10.1093\/nargab\/lqaa059","article-title":"Normalizing single-cell RNA sequencing data with internal spike-in-like genes","volume":"2","author":"Lin","year":"2020","journal-title":"NAR Genom. Bioinform."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8624963","DOI":"10.1155\/2020\/8624963","article-title":"The Application of Single-Cell RNA Sequencing in Vaccinology","volume":"2020","author":"Noe","year":"2020","journal-title":"J. Immunol. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/s41591-021-01329-2","article-title":"Single-cell multi-omics analysis of the immune response in COVID-19","volume":"27","author":"Stephenson","year":"2021","journal-title":"Nat. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.cell.2020.10.028","article-title":"Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection","volume":"184","author":"Wei","year":"2021","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ravindra, N.G., Alfajaro, M.M., Gasque, V., Huston, N.C., Wan, H., Szigeti-Buck, K., Yasumoto, Y., Greaney, A.M., Habet, V., and Chow, R.D. (2021). Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes. PLoS Biol., 19.","DOI":"10.1371\/journal.pbio.3001143"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"108175","DOI":"10.1016\/j.celrep.2020.108175","article-title":"A Single-Cell RNA Expression Map of Human Coronavirus Entry Factors","volume":"32","author":"Singh","year":"2020","journal-title":"Cell Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"317","DOI":"10.3389\/fgene.2019.00317","article-title":"Single-Cell RNA-Seq Technologies and Related Computational Data Analysis","volume":"10","author":"Chen","year":"2019","journal-title":"Front. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.coviro.2018.03.001","article-title":"The use of single-cell RNA-Seq to understand virus-host interactions","volume":"29","author":"Cristinelli","year":"2018","journal-title":"Curr. Opin. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e01342-18","DOI":"10.1128\/JVI.01342-18","article-title":"Going the Distance: Optimizing RNA-Seq Strategies for Transcriptomic Analysis of Complex Viral Genomes","volume":"93","author":"Depledge","year":"2019","journal-title":"J. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e8746","DOI":"10.15252\/msb.20188746","article-title":"Current best practices in single-cell RNA-seq analysis: A tutorial","volume":"15","author":"Luecken","year":"2019","journal-title":"Mol. Syst Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1038\/nmeth.2657","article-title":"Image-based transcriptomics in thousands of single human cells at single-molecule resolution","volume":"10","author":"Battich","year":"2013","journal-title":"Nat. Methods"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"aaa6090","DOI":"10.1126\/science.aaa6090","article-title":"RNA imaging. Spatially resolved, highly multiplexed RNA profiling in single cells","volume":"348","author":"Chen","year":"2015","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/nmeth.2892","article-title":"Single-cell in situ RNA profiling by sequential hybridization","volume":"11","author":"Lubeck","year":"2014","journal-title":"Nat. Methods"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"jcs.252544","DOI":"10.1242\/jcs.252544","article-title":"Cell-to-cell and genome-to-genome variability of adenovirus transcription tuned by the cell cycle","volume":"134","author":"Suomalainen","year":"2020","journal-title":"J. Cell Sci."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Witte, R., Andriasyan, V., Georgi, F., Yakimovich, A., and Greber, U.F. (2018). Concepts in Light Microscopy of Viruses. Viruses, 10.","DOI":"10.3390\/v10040202"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Wang, I.H., Burckhardt, C.J., Yakimovich, A., and Greber, U.F. (2018). Imaging, Tracking and Computational Analyses of Virus Entry and Egress with the Cytoskeleton. Viruses, 10.","DOI":"10.3390\/v10040166"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1111\/tra.12387","article-title":"Principles of Virus Uncoating: Cues and the Snooker Ball","volume":"17","author":"Yamauchi","year":"2016","journal-title":"Traffic"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3802","DOI":"10.1128\/JVI.02568-15","article-title":"Virus and Host Mechanics Support Membrane Penetration and Cell Entry","volume":"90","author":"Greber","year":"2016","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"277","DOI":"10.3390\/cells4030277","article-title":"Misdelivery at the Nuclear Pore Complex-Stopping a Virus Dead in Its Tracks","volume":"4","author":"Flatt","year":"2015","journal-title":"Cells"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/s41586-019-1369-y","article-title":"scSLAM-seq reveals core features of transcription dynamics in single cells","volume":"571","author":"Erhard","year":"2019","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/nmeth.1321","article-title":"Imaging intracellular RNA distribution and dynamics in living cells","volume":"6","author":"Tyagi","year":"2009","journal-title":"Nat. Methods"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.cell.2014.09.039","article-title":"A Protein-Tagging System for Signal Amplification in Gene Expression and Fluorescence Imaging","volume":"159","author":"Tanenbaum","year":"2014","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1038\/s41592-019-0531-7","article-title":"Live imaging of mRNA using RNA-stabilized fluorogenic proteins","volume":"16","author":"Wu","year":"2019","journal-title":"Nat. Methods"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1021\/acs.chemrev.9b00692","article-title":"Single-Virus Tracking: From Imaging Methodologies to Virological Applications","volume":"120","author":"Liu","year":"2020","journal-title":"Chem. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e01002-20","DOI":"10.1128\/AAC.01002-20","article-title":"The FDA-approved drug Nelfinavir inhibits lytic cell-free, but not cell-associated non-lytic transmission of human adenovirus","volume":"64","author":"Georgi","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1002\/j.1460-2075.1996.tb00525.x","article-title":"The role of the adenovirus protease on virus entry into cells","volume":"15","author":"Greber","year":"1996","journal-title":"EMBO J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"12367","DOI":"10.1128\/JVI.01833-13","article-title":"A direct and versatile assay measuring membrane penetration of adenovirus in single cells","volume":"87","author":"Suomalainen","year":"2013","journal-title":"J. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Ostapchuk, P., Suomalainen, M., Zheng, Y., Boucke, K., Greber, U.F., and Hearing, P. (2017). The adenovirus major core protein VII is dispensable for virion assembly but is essential for lytic infection. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006455"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"13699","DOI":"10.1073\/pnas.1920896117","article-title":"Dynamic competition for hexon binding between core protein VII and lytic protein VI promotes adenovirus maturation and entry","volume":"117","author":"Suomalainen","year":"2020","journal-title":"Proc. Natl. Acad Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1186\/1743-422X-6-174","article-title":"Genetic reconstitution of the human adenovirus type 2 temperature-sensitive 1 mutant defective in endosomal escape","volume":"6","author":"Imelli","year":"2009","journal-title":"Virol. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1111\/j.1600-0854.2008.00835.x","article-title":"Infectious adenovirus type 2 transport through early but not late endosomes","volume":"9","author":"Gastaldelli","year":"2008","journal-title":"Traffic"},{"key":"ref_49","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_50","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.jviromet.2009.04.010","article-title":"Accurate single-day titration of adenovirus vectors based on equivalence of protein VII nuclear dots and infectious particles","volume":"159","author":"Walkiewicz","year":"2009","journal-title":"J. Virol. Methods"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5998","DOI":"10.1093\/emboj\/16.19.5998","article-title":"The role of the nuclear pore complex in adenovirus DNA entry","volume":"16","author":"Greber","year":"1997","journal-title":"EMBO J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1128\/JVI.01571-10","article-title":"Stepwise loss of fluorescent core protein V from human adenovirus during entry into cells","volume":"85","author":"Puntener","year":"2011","journal-title":"J. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Stichling, N., Suomalainen, M., Flatt, J.W., Schmid, M., Pacesa, M., Hemmi, S., Jungraithmayr, W., Maler, M.D., Freudenberg, M.A., and Pluckthun, A. (2018). Lung macrophage scavenger receptor SR-A6 (MARCO) is an adenovirus type-specific virus entry receptor. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1006914"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3419","DOI":"10.1002\/1873-3468.13690","article-title":"Imaging the adenovirus infection cycle","volume":"593","author":"Pied","year":"2019","journal-title":"FEBS Lett."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1006\/mthe.2001.0414","article-title":"Variation in adenovirus receptor expression and adenovirus vector-mediated transgene expression at defined stages of the cell cycle","volume":"4","author":"Seidman","year":"2001","journal-title":"Mol. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.chom.2011.07.006","article-title":"Drifting motions of the adenovirus receptor CAR and immobile integrins initiate virus uncoating and membrane lytic protein exposure","volume":"10","author":"Burckhardt","year":"2011","journal-title":"Cell Host Microbe"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Wodrich, H., Henaff, D., Jammart, B., Segura-Morales, C., Seelmeir, S., Coux, O., Ruzsics, Z., Wiethoff, C.M., and Kremer, E.J. (2010). A capsid-encoded PPxY-motif facilitates adenovirus entry. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000808"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.chom.2015.06.006","article-title":"Co-option of Membrane Wounding Enables Virus Penetration into Cells","volume":"18","author":"Luisoni","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2604","DOI":"10.1128\/JVI.79.4.2604-2613.2005","article-title":"Early steps of clathrin-mediated endocytosis involved in phagosomal escape of Fcgamma receptor-targeted adenovirus","volume":"79","author":"Meier","year":"2005","journal-title":"J. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1083\/jcb.200112067","article-title":"Adenovirus triggers macropinocytosis and endosomal leakage together with its clathrin-mediated uptake","volume":"158","author":"Meier","year":"2002","journal-title":"J. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1242\/jcs.203794","article-title":"The nuclear export factor CRM1 controls juxta-nuclear microtubule-dependent virus transport","volume":"130","author":"Wang","year":"2017","journal-title":"J. Cell Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.chom.2011.08.010","article-title":"Kinesin-1-mediated capsid disassembly and disruption of the nuclear pore complex promote virus infection","volume":"10","author":"Strunze","year":"2011","journal-title":"Cell Host Microbe"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3785","DOI":"10.1016\/j.celrep.2019.11.064","article-title":"The E3 Ubiquitin Ligase Mind Bomb 1 Controls Adenovirus Genome Release at the Nuclear Pore Complex","volume":"29","author":"Bauer","year":"2019","journal-title":"Cell Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.3389\/fmicb.2016.01503","article-title":"Components of Adenovirus Genome Packaging","volume":"7","author":"Ahi","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Condezo, G.N., and San Martin, C. (2017). Localization of adenovirus morphogenesis players, together with visualization of assembly intermediates and failed products, favor a model where assembly and packaging occur concurrently at the periphery of the replication center. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006320"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1002\/(SICI)1099-1654(1998100)8:4<213::AID-RMV225>3.0.CO;2-W","article-title":"Virus assembly and disassembly: The adenovirus cysteine protease as a trigger factor","volume":"8","author":"Greber","year":"1998","journal-title":"Rev. Med. Virol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4536","DOI":"10.3390\/v6114536","article-title":"Structure, Function and Dynamics in Adenovirus Maturation","volume":"6","author":"Mangel","year":"2014","journal-title":"Viruses"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"9653","DOI":"10.1128\/JVI.01453-15","article-title":"Structures of Adenovirus Incomplete Particles Clarify Capsid Architecture and Show Maturation Changes of Packaging Protein L1 52\/55k","volume":"89","author":"Condezo","year":"2015","journal-title":"J. Virol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"102543","DOI":"10.1016\/j.isci.2021.102543","article-title":"Microscopy deep learning predicts virus infections and reveals mechanics of lytic-infected cells","volume":"24","author":"Andriasyan","year":"2021","journal-title":"iScience"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"102543","DOI":"10.1128\/JVI.00166-17","article-title":"Simultaneous Single-Cell In Situ Analysis of Human Adenovirus Type 5 DNA and mRNA Expression Patterns in Lytic and Persistent Infection","volume":"91","author":"Krzywkowski","year":"2017","journal-title":"J. Virol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Zheng, Y., Stamminger, T., and Hearing, P. (2016). E2F\/Rb Family Proteins Mediate Interferon Induced Repression of Adenovirus Immediate Early Transcription to Promote Persistent Viral Infection. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005415"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1038\/s41467-020-15844-2","article-title":"The UPR sensor IRE1alpha and the adenovirus E3-19K glycoprotein sustain persistent and lytic infections","volume":"11","author":"Prasad","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1084\/jem.99.2.167","article-title":"Plaque formation and isolation of pure lines with poliomyelitis viruses","volume":"99","author":"Dulbecco","year":"1954","journal-title":"J. Exp. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3571","DOI":"10.1002\/1873-3468.13576","article-title":"Adenovirus persistence, reactivation, and clinical management","volume":"593","author":"Lion","year":"2019","journal-title":"FEBS Lett."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1097\/QCO.0000000000000451","article-title":"Human adenovirus infections: Update and consideration of mechanisms of viral persistence","volume":"31","author":"Radke","year":"2018","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1016\/j.celrep.2017.10.051","article-title":"Single-Cell Virology: On-Chip Investigation of Viral Infection Dynamics","volume":"21","author":"Guo","year":"2017","journal-title":"Cell Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1099\/jgv.0.001557","article-title":"Egress of non-enveloped enteric RNA viruses","volume":"102","author":"Owusu","year":"2021","journal-title":"J. Gen. Virol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1016\/j.cell.2020.10.019","article-title":"Translation and Replication Dynamics of Single RNA Viruses","volume":"183","author":"Boersma","year":"2020","journal-title":"Cell"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/nrmicro3367","article-title":"At the centre: Influenza A virus ribonucleoproteins","volume":"13","author":"Eisfeld","year":"2015","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Simpson, C., and Yamauchi, Y. (2020). Microtubules in Influenza Virus Entry and Egress. Viruses, 12.","DOI":"10.3390\/v12010117"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3155","DOI":"10.1128\/JVI.02284-12","article-title":"Most influenza a virions fail to express at least one essential viral protein","volume":"87","author":"Brooke","year":"2013","journal-title":"J. Virol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3155","DOI":"10.1128\/JVI.00559-19","article-title":"Innate Immune Response to Influenza Virus at Single-Cell Resolution in Human Epithelial Cells Revealed Paracrine Induction of Interferon Lambda 1","volume":"93","author":"Ramos","year":"2019","journal-title":"J. Virol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e00559-19","DOI":"10.1128\/JVI.00500-19","article-title":"Single-Cell Virus Sequencing of Influenza Infections That Trigger Innate Immunity","volume":"93","author":"Russell","year":"2019","journal-title":"J. Virol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e32303","DOI":"10.7554\/eLife.32303","article-title":"Extreme heterogeneity of influenza virus infection in single cells","volume":"7","author":"Russell","year":"2018","journal-title":"eLife"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Sun, J., Vera, J.C., Drnevich, J., Lin, Y.T., Ke, R., and Brooke, C.B. (2020). Single cell heterogeneity in influenza A virus gene expression shapes the innate antiviral response to infection. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008671"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e02880-19","DOI":"10.1128\/mBio.02880-19","article-title":"Cell-to-Cell Variation in Defective Virus Expression and Effects on Host Responses during Influenza Virus Infection","volume":"11","author":"Wang","year":"2020","journal-title":"mBio"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Kupke, S.Y., Ly, L.H., Borno, S.T., Ruff, A., Timmermann, B., Vingron, M., Haas, S., and Reichl, U. (2020). Single-Cell Analysis Uncovers a Vast Diversity in Intracellular Viral Defective Interfering RNA Content Affecting the Large Cell-to-Cell Heterogeneity in Influenza A Virus Replication. Viruses, 12.","DOI":"10.3390\/v12010071"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.tim.2020.02.006","article-title":"Defective Interfering Particles of Negative-Strand RNA Viruses","volume":"28","author":"Ziegler","year":"2020","journal-title":"Trends Microbiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e00354-19","DOI":"10.1128\/JVI.00354-19","article-title":"Sequencing Framework for the Sensitive Detection and Precise Mapping of Defective Interfering Particle-Associated Deletions across Influenza A and B Viruses","volume":"93","author":"Alnaji","year":"2019","journal-title":"J. Virol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"8064","DOI":"10.1128\/JVI.00240-13","article-title":"Sequence analysis of in vivo defective interfering-like RNA of influenza A H1N1 pandemic virus","volume":"87","author":"Saira","year":"2013","journal-title":"J. Virol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1128\/JVI.01164-17","article-title":"Population Diversity and Collective Interactions during Influenza Virus Infection","volume":"91","author":"Brooke","year":"2017","journal-title":"J. Virol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"17399","DOI":"10.1073\/pnas.1907031116","article-title":"An influenza virus-triggered SUMO switch orchestrates co-opted endogenous retroviruses to stimulate host antiviral immunity","volume":"116","author":"Schmidt","year":"2019","journal-title":"Proc. Natl. Acad Sci. USA"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Chou, Y.Y., Heaton, N.S., Gao, Q., Palese, P., Singer, R.H., and Lionnet, T. (2013). Colocalization of different influenza viral RNA segments in the cytoplasm before viral budding as shown by single-molecule sensitivity FISH analysis. PLoS Pathog., 9.","DOI":"10.1371\/annotation\/8f53e7f2-2348-436f-b37e-a883a01e9bbd"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1073\/pnas.1812632116","article-title":"Real-time dissection of dynamic uncoating of individual influenza viruses","volume":"116","author":"Qin","year":"2019","journal-title":"Proc. Natl. Acad Sci. USA"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/s41564-018-0332-2","article-title":"Influenza virus uses transportin 1 for vRNP debundling during cell entry","volume":"4","author":"Miyake","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e01248-16","DOI":"10.1128\/mBio.01248-16","article-title":"Complete and Incomplete Genome Packaging of Influenza A and B Viruses","volume":"7","author":"Nakatsu","year":"2016","journal-title":"mBio"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"16854","DOI":"10.1073\/pnas.1415396111","article-title":"Influenza A virus nucleoprotein selectively decreases neuraminidase gene-segment packaging while enhancing viral fitness and transmissibility","volume":"111","author":"Brooke","year":"2014","journal-title":"Proc. Natl. Acad Sci. USA"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e01778-18","DOI":"10.1128\/JVI.01778-18","article-title":"West Nile Virus-Inclusive Single-Cell RNA Sequencing Reveals Heterogeneity in the Type I Interferon Response within Single Cells","volume":"93","author":"Upadhyay","year":"2019","journal-title":"J. Virol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e32942","DOI":"10.7554\/eLife.32942","article-title":"Single-cell transcriptional dynamics of flavivirus infection","volume":"7","author":"Zanini","year":"2018","journal-title":"eLife"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"E12363","DOI":"10.1073\/pnas.1813819115","article-title":"Virus-inclusive single-cell RNA sequencing reveals the molecular signature of progression to severe dengue","volume":"115","author":"Zanini","year":"2018","journal-title":"Proc. Natl. Acad Sci. USA"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e46339","DOI":"10.7554\/eLife.46339","article-title":"HSV-1 single cell analysis reveals anti-viral and developmental programs activation in distinct sub-populations","volume":"8","author":"Drayman","year":"2019","journal-title":"eLife"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Pond, K.W., Doubrovinski, K., and Thorne, C.A. (2020). Wnt\/beta-catenin Signaling in Tissue Self-Organization. Genes, 11.","DOI":"10.3390\/genes11080939"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"dev165902","DOI":"10.1242\/dev.165902","article-title":"Wnt signalling: Conquering complexity","volume":"145","author":"Wiese","year":"2018","journal-title":"Development"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1146\/annurev.immunol.24.021605.090552","article-title":"Genetic analysis of host resistance: Toll-like receptor signaling and immunity at large","volume":"24","author":"Beutler","year":"2006","journal-title":"Annu. Rev. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/s41577-020-0288-3","article-title":"RIG-I-like receptors: Their regulation and roles in RNA sensing","volume":"20","author":"Rehwinkel","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/s41590-019-0556-1","article-title":"Regulation of cGAS- and RLR-mediated immunity to nucleic acids","volume":"21","author":"Ablasser","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1146\/annurev-virology-092818-015756","article-title":"Interferon-Stimulated Genes: What Do They All Do?","volume":"6","author":"Schoggins","year":"2019","journal-title":"Annu. Rev. Virol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.chom.2017.07.012","article-title":"Ten Strategies of Interferon Evasion by Viruses","volume":"22","year":"2017","journal-title":"Cell Host Microbe"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.virusres.2015.02.003","article-title":"Influenza virus activation of the interferon system","volume":"209","author":"Killip","year":"2015","journal-title":"Virus Res."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Munoz-Moreno, R., Martinez-Romero, C., and Garcia-Sastre, A. (2020). Induction and Evasion of Type-I Interferon Responses during Influenza A Virus Infection. Cold Spring Harb. Perspect Med., a038414.","DOI":"10.1101\/cshperspect.a038414"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Martin, B.E., Harris, J.D., Sun, J., Koelle, K., and Brooke, C.B. (2020). Cellular co-infection can modulate the efficiency of influenza A virus production and shape the interferon response. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008974"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/imr.12699","article-title":"Antiviral interferon response at single-cell resolution","volume":"285","author":"Talemi","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.virol.2010.08.008","article-title":"Heterocellular induction of interferon by negative-sense RNA viruses","volume":"407","author":"Chen","year":"2010","journal-title":"Virology"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Zhao, M., Zhang, J., Phatnani, H., Scheu, S., and Maniatis, T. (2012). Stochastic expression of the interferon-beta gene. PLoS Biol., 10.","DOI":"10.1371\/journal.pbio.1001249"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1039\/C7IB00146K","article-title":"Single-cell analysis of early antiviral gene expression reveals a determinant of stochastic IFNB1 expression","volume":"9","author":"Doganay","year":"2017","journal-title":"Integr. Biol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"16303","DOI":"10.1073\/pnas.1005077107","article-title":"Preference of RIG-I for short viral RNA molecules in infected cells revealed by next-generation sequencing","volume":"107","author":"Baum","year":"2010","journal-title":"Proc. Natl. Acad Sci. USA"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1128\/JVI.78.4.1706-1717.2004","article-title":"Innate cellular response to virus particle entry requires IRF3 but not virus replication","volume":"78","author":"Collins","year":"2004","journal-title":"J. Virol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"5532","DOI":"10.1128\/JVI.76.11.5532-5539.2002","article-title":"Transcriptional profiling of interferon regulatory factor 3 target genes: Direct involvement in the regulation of interferon-stimulated genes","volume":"76","author":"Grandvaux","year":"2002","journal-title":"J. Virol."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Kelly, J.N., Laloli, L., V\u2019kovski, P., Holwerda, M., Portmann, J., Thiel, V., and Dijkman, R. (2020). Comprehensive single cell analysis of pandemic influenza A virus infection in the human airways uncovers cell-type specific host transcriptional signatures relevant for disease progression and pathogenesis. bioRxiv.","DOI":"10.1101\/2020.04.03.014282"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.cels.2018.05.008","article-title":"Dissection of Influenza Infection In Vivo by Single-Cell RNA Sequencing","volume":"7","author":"Steuerman","year":"2018","journal-title":"Cell Syst."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Zhang, J., Liu, J., Yuan, Y., Huang, F., Ma, R., Luo, B., Xi, Z., Pan, T., Liu, B., and Zhang, Y. (2020). Two waves of pro-inflammatory factors are released during the influenza A virus (IAV)-driven pulmonary immunopathogenesis. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008334"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Cao, Y., Guo, Z., Vangala, P., Donnard, E., Liu, P., McDonel, P., Ordovas-Montanes, J., Shalek, A.K., Finberg, R.W., and Wang, J.P. (2020). Single-cell analysis of upper airway cells reveals host-viral dynamics in influenza infected adults. bioRxiv.","DOI":"10.1101\/2020.04.15.042978"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"4620","DOI":"10.1073\/pnas.0308001101","article-title":"Human and avian influenza viruses target different cell types in cultures of human airway epithelium","volume":"101","author":"Matrosovich","year":"2004","journal-title":"Proc. Natl. Acad Sci. USA"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"8060","DOI":"10.1128\/JVI.00384-06","article-title":"Infection of human airway epithelium by human and avian strains of influenza a virus","volume":"80","author":"Thompson","year":"2006","journal-title":"J. Virol."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Fay, E.J., Aron, S.L., Macchietto, M.G., Markman, M.W., Esser-Nobis, K., Gale, M., Shen, S., and Langlois, R.A. (2020). Cell type- and replication stage-specific influenza virus responses in vivo. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008760"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"9610","DOI":"10.1073\/pnas.1807516115","article-title":"Distinct antiviral signatures revealed by the magnitude and round of influenza virus replication in vivo","volume":"115","author":"Sjaastad","year":"2018","journal-title":"Proc. Natl. Acad Sci. USA"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"3539","DOI":"10.1016\/j.celrep.2019.11.021","article-title":"Visualizing the Selectivity and Dynamics of Interferon Signaling In Vivo","volume":"29","author":"Stifter","year":"2019","journal-title":"Cell Rep."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1038\/s41467-020-15072-8","article-title":"Acid ceramidase of macrophages traps herpes simplex virus in multivesicular bodies and protects from severe disease","volume":"11","author":"Lang","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1183\/09031936.00186214","article-title":"Influenza virus-induced lung injury: Pathogenesis and implications for treatment","volume":"45","author":"Herold","year":"2015","journal-title":"Eur. Respir. J."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1002\/JLB.4RU0820-232R","article-title":"From virus to inflammation, how influenza promotes lung damage","volume":"110","author":"Klomp","year":"2021","journal-title":"J. Leukoc. Biol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.cell.2020.09.056","article-title":"Chromatin Potential Identified by Shared Single-Cell Profiling of RNA and Chromatin","volume":"183","author":"Ma","year":"2020","journal-title":"Cell"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"eaax2656","DOI":"10.1126\/science.aax2656","article-title":"Expansion sequencing: Spatially precise in situ transcriptomics in intact biological systems","volume":"371","author":"Alon","year":"2021","journal-title":"Science"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41592-020-01038-7","article-title":"Spatially resolved transcriptomics adds a new dimension to genomics","volume":"18","author":"Larsson","year":"2021","journal-title":"Nat. Methods"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41592-020-01037-8","article-title":"Spatially resolved single-cell genomics and transcriptomics by imaging","volume":"18","author":"Zhuang","year":"2021","journal-title":"Nat. Methods"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"e105912","DOI":"10.15252\/embj.2020105912","article-title":"An organoid-derived bronchioalveolar model for SARS-CoV-2 infection of human alveolar type II-like cells","volume":"40","author":"Lamers","year":"2021","journal-title":"EMBO J."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"e103476","DOI":"10.15252\/embj.2019103476","article-title":"Multilineage murine stem cells generate complex organoids to model distal lung development and disease","volume":"39","author":"Heiner","year":"2020","journal-title":"EMBO J."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"e1900271","DOI":"10.1002\/pmic.201900271","article-title":"Single-Cell Multi-Omics and Its Prospective Application in Cancer Biology","volume":"20","author":"Peng","year":"2020","journal-title":"Proteomics"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.3389\/fmicb.2020.01152","article-title":"Single Cell Metabolomics: A Future Tool to Unmask Cellular Heterogeneity and Virus-Host Interaction in Context of Emerging Viral Diseases","volume":"11","author":"Kumar","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/s41580-020-0231-2","article-title":"Proteomic and interactomic insights into the molecular basis of cell functional diversity","volume":"21","author":"Bludau","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1146\/annurev-virology-010320-070410","article-title":"Post-Translation Regulation of Influenza Virus Replication","volume":"7","author":"Dawson","year":"2020","journal-title":"Annu. Rev. Virol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"e1619","DOI":"10.1002\/wrna.1619","article-title":"Emerging translation strategies during virus-host interaction","volume":"12","author":"Hoang","year":"2021","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/nature22794","article-title":"Rare cell variability and drug-induced reprogramming as a mode of cancer drug resistance","volume":"546","author":"Shaffer","year":"2017","journal-title":"Nature"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.cell.2020.07.003","article-title":"Memory Sequencing Reveals Heritable Single-Cell Gene Expression Programs Associated with Distinct Cellular Behaviors","volume":"182","author":"Shaffer","year":"2020","journal-title":"Cell"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"102291","DOI":"10.1016\/j.isci.2021.102291","article-title":"A transient heritable memory regulates HIV reactivation from latency","volume":"24","author":"Lu","year":"2021","journal-title":"iScience"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/8\/1568\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:42:41Z","timestamp":1760164961000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/8\/1568"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,9]]},"references-count":144,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["v13081568"],"URL":"https:\/\/doi.org\/10.3390\/v13081568","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,9]]}}}