{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T20:10:42Z","timestamp":1769285442680,"version":"3.49.0"},"reference-count":72,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Veterans Affairs Merit Review","award":["1101 BX004516-01A1"],"award-info":[{"award-number":["1101 BX004516-01A1"]}]},{"name":"Tulane University Health Sciences Center"},{"name":"Seed Grant from the Louisiana Cancer Research Center"},{"name":"Akdamar Fellowship Program"},{"name":"Department of Gastroenterology and Hepatology, Tulane University Health Science Center"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The concentration of extracellular vesicles (EVs) in the peripheral blood of COVID-19 patients is increased. Nevertheless, their potential role in the transmission of infection remains unclear. This study was performed to determine whether EVs produced by the sub-genomic replicon system developed in Baby Hamster Kidney (BHK-21) cells could transfer SARS-CoV-2 replicon RNA, leading to the establishment of a viral replication system in human cells. Purified EVs from the SARS-CoV-2 sub-genomic replicon cell line BHK-21 were cultured with a naive human cell line. The success of EV-mediated transfer of SARS-CoV-2 replicon RNA and its productive replication was assessed using G-418 selection, a luciferase assay, immunostaining, and Western blot. We found that the A549 cell line cultured with EVs isolated from SARS-CoV-2 BHK-21 replicon cells developed G-418-resistant cell colonies. SARS-COV-2 RNA replication in A549 cells was confirmed by nano luciferase, Nsp1 protein. SARS-CoV-2 RNA replication causes massive morphological changes. Treatment of cells with the FDA-approved Paxlovid demonstrated a dose-dependent inhibition of viral replication. We isolated two human epithelial cell lines (gastrointestinal and neuroblastoma) and one vascular endothelial cell line that stably support high-level replication of SARS-CoV-2 sub-genomic RNA. Viral elimination did not revert the abnormal cellular shape, vesicle accumulation, syncytia formation, or EV release. Our study\u2019s findings highlight the potential implications of EV-mediated transfer of replicon RNA to permissive cells. The replicon model is a valuable tool for studying virus-induced reversible and irreversible cellular reprogramming, as well as for testing novel therapeutic strategies for SARS-CoV-2.<\/jats:p>","DOI":"10.3390\/v18010145","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T10:41:34Z","timestamp":1769164894000},"page":"145","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Virion-Independent Extracellular Vesicle (EV)-Dependent Transmission of SARS-CoV-2 as a Potential New Mechanism of Viral RNA Spread in Human Cells"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7921-3169","authenticated-orcid":false,"given":"Nergiz","family":"Ekmen","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Tulane University Health Sciences Center, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5693-5951","authenticated-orcid":false,"given":"Ali Riza","family":"Koksal","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Di","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6483-6259","authenticated-orcid":false,"given":"Paul","family":"Thevenot","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Institute of Translational Research, Ochsner Health, New Orleans, LA 70121, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Glover","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Tulane University Health Sciences Center, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Srikanta","family":"Dash","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Tulane University Health Sciences Center, New Orleans, LA 70112, USA"},{"name":"Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA"},{"name":"Southeast Louisiana Veterans Health Care System, 2400 Canal Street, New Orleans, LA 70119, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"A novel coronavirus from patients with pneumonia in China, 2019","volume":"382","author":"Zhu","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"576","DOI":"10.21037\/atm-20-2124","article-title":"Clinical features of severe patients infected with 2019 novel coronavirus: A systematic review and meta-analysis","volume":"8","author":"Huang","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Odilov, A., Volkov, A., Abdullaev, A., Gasanova, T., Lipina, T., and Babichenko, I. (2021). COVID-19: Multiorgan dissemination of SARS-CoV-2 is driven by pulmonary factors. Viruses, 14.","DOI":"10.3390\/v14010039"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/nri855","article-title":"Exosomes: Composition, biogenesis and function","volume":"2","author":"Zitvogel","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Li, B., Li, W., Liu, T., and Zha, L. (2023). Extracellular vesicles regulate the transmission of insulin resistance and redefine noncommunicable diseases. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.1024786"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Aloi, N., Drago, G., Ruggieri, S., Cibella, F., Colombo, P., and Longo, V. (2024). Extracellular vesicles and immunity: At the crossroads of cell communication. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25021205"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1080\/15548627.2021.1987673","article-title":"Extracellular vesicles originating from autophagy mediate an antibody-resistant spread of classical swine fever virus in cell culture","volume":"18","author":"Wang","year":"2022","journal-title":"Autophagy"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Moulin, C., Crupi, M.J., Ilkow, C.S., Bell, J.C., and Boulton, S. (2023). Extracellular vesicles and viruses: Two intertwined entities. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021036"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Martins, S.d.T., and Alves, L.R. (2020). Extracellular vesicles in viral infections: Two sides of the same coin?. Front. Cell. Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.593170"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"100659","DOI":"10.1016\/j.bj.2023.100659","article-title":"The Yin and the Yang of extracellular vesicles during viral infections","volume":"47","author":"Martin","year":"2024","journal-title":"Biomed. J."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Aydin, Y., Koksal, A.R., Reddy, V., Lin, D., Osman, H., Heidari, Z., Rhadhi, S.M., Wimley, W.C., Parsi, M.A., and Dash, S. (2021). Extracellular vesicle release promotes viral replication during persistent HCV infection. Cells, 10.","DOI":"10.3390\/cells10050984"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/nature12029","article-title":"A pathogenic picornavirus acquires an envelope by hijacking cellular membranes","volume":"496","author":"Feng","year":"2013","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"13109","DOI":"10.1073\/pnas.1221899110","article-title":"Exosome-mediated transmission of hepatitis C virus between human hepatoma Huh7. 5 cells","volume":"110","author":"Ramakrishnaiah","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/hep.21959","article-title":"Hepatitis C virus cell-cell transmission in hepatoma cells in the presence of neutralizing antibodies","volume":"47","author":"Timpe","year":"2008","journal-title":"Hepatology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1111\/j.1365-2893.2008.01010.x","article-title":"Active intravenous drug use during chronic hepatitis C therapy does not reduce sustained virological response rates in adherent patients","volume":"15","author":"Bruggmann","year":"2008","journal-title":"J. Viral Hepat."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1084\/jem.20090766","article-title":"Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation","volume":"207","author":"Fofana","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2834","DOI":"10.1002\/eji.200424887","article-title":"Association of hepatitis C virus envelope proteins with exosomes","volume":"34","author":"Masciopinto","year":"2004","journal-title":"Eur. J. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.virol.2011.11.009","article-title":"Regulation of hepatitis C virus secretion by the Hrs-dependent exosomal pathway","volume":"422","author":"Tamai","year":"2012","journal-title":"Virology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.chom.2012.08.010","article-title":"Short-range exosomal transfer of viral RNA from infected cells to plasmacytoid dendritic cells triggers innate immunity","volume":"12","author":"Dreux","year":"2012","journal-title":"Cell Host Microbe"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"335","DOI":"10.5483\/BMBRep.2023-0073","article-title":"The complex role of extracellular vesicles in HIV infection","volume":"56","author":"Lee","year":"2023","journal-title":"BMB Rep."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Jacob, V., Lambour, A., Swinyard, B., Zerbib, Y., Diouf, M., Soudet, S., Brochot, E., Six, I., Maizel, J., and Slama, M. (2023). Annexin-V positive extracellular vesicles level is increased in severe COVID-19 disease. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1186122"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"165878","DOI":"10.1016\/j.bbadis.2020.165878","article-title":"Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach","volume":"1866","author":"Naqvi","year":"2020","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Basis Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41580-021-00432-z","article-title":"Structures and functions of coronavirus replication\u2013transcription complexes and their relevance for SARS-CoV-2 drug design","volume":"23","author":"Malone","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s00018-022-04469-x","article-title":"The double-membrane vesicle (DMV): A virus-induced organelle dedicated to the replication of SARS-CoV-2 and other positive-sense single-stranded RNA viruses","volume":"79","author":"Roingeard","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1016\/j.tim.2020.05.009","article-title":"Double-membrane vesicles as platforms for viral replication","volume":"28","author":"Wolff","year":"2020","journal-title":"Trends Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2206095","DOI":"10.1002\/advs.202206095","article-title":"A Review of Extracellular Vesicles in COVID-19 Diagnosis, Treatment, and Prevention","volume":"10","author":"Su","year":"2023","journal-title":"Adv. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1007\/s00253-023-12468-6","article-title":"Extracellular vesicles in COVID-19 prognosis, treatment, and vaccination: An update","volume":"107","author":"Carrero","year":"2023","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e02216-02221","DOI":"10.1128\/jvi.02216-21","article-title":"Stable cell clones harboring self-replicating SARS-CoV-2 RNAs for drug screen","volume":"96","author":"Liu","year":"2022","journal-title":"J. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.2147\/JHC.S423043","article-title":"A Single-Step Immunocapture Assay to Quantify HCC Exosomes Using the Highly Sensitive Fluorescence Nanoparticle-Tracking Analysis","volume":"10","author":"Koksal","year":"2023","journal-title":"J. Hepatocell. Carcinoma"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1528109","DOI":"10.1080\/20013078.2018.1528109","article-title":"Precipitation with polyethylene glycol followed by washing and pelleting by ultracentrifugation enriches extracellular vesicles from tissue culture supernatants in small and large scales","volume":"7","author":"Ludwig","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5885","DOI":"10.1038\/s41467-020-19619-7","article-title":"SARS-CoV-2 structure and replication characterized by in situ cryo-electron tomography","volume":"11","author":"Klein","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.livres.2023.09.004","article-title":"Prolonged existence of SARS-CoV-2 RNAs in the extracellular vesicles of respiratory specimens from patients with negative reverse transcription-polymerase chain reaction","volume":"7","author":"Subudhi","year":"2023","journal-title":"Liver Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41421-022-00510-2","article-title":"Extracellular vesicles mediate antibody-resistant transmission of SARS-CoV-2","volume":"9","author":"Xia","year":"2023","journal-title":"Cell Discov."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1093\/jmcb\/mjaa042","article-title":"Cytoskeleton\u2014A crucial key in host cell for coronavirus infection","volume":"12","author":"Wen","year":"2020","journal-title":"J. Mol. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Cortes-Galvez, D., Dangerfield, J.A., and Metzner, C. (2023). Extracellular vesicles and their membranes: Exosomes vs. Virus-related particles. Membranes, 13.","DOI":"10.3390\/membranes13040397"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"65","DOI":"10.2144\/000114575","article-title":"Ion-exchange chromatography purification of extracellular vesicles","volume":"63","year":"2017","journal-title":"Biotechniques"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1007\/s10529-023-03430-7","article-title":"Chromatographic purification of small extracellular vesicles using an affinity column for phospholipid membranes","volume":"45","author":"Masaki","year":"2023","journal-title":"Biotechnol. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"115242","DOI":"10.1016\/j.jviromet.2025.115242","article-title":"Effective RNA extraction with readily available reagents: A comparative analysis of alternative protocols","volume":"338","author":"Dias","year":"2025","journal-title":"J. Virol. Methods"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1038\/s12276-022-00898-7","article-title":"Dissecting exosome inhibitors: Therapeutic insights into small-molecule chemicals against cancer","volume":"54","author":"Kim","year":"2022","journal-title":"Exp. Mol. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"17145","DOI":"10.1074\/jbc.R115.640359","article-title":"Intermediate filaments play a pivotal role in regulating cell architecture and function","volume":"290","author":"Lowery","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/s41423-023-01122-w","article-title":"SARS-CoV-2 immunity in animal models","volume":"21","author":"Chen","year":"2024","journal-title":"Cell. Mol. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e106267","DOI":"10.15252\/embj.2020106267","article-title":"Syncytia formation by SARS-CoV-2-infected cells","volume":"39","author":"Buchrieser","year":"2020","journal-title":"EMBO J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"103104","DOI":"10.1016\/j.ebiom.2020.103104","article-title":"Persistence of viral RNA, pneumocyte syncytia and thrombosis are hallmarks of advanced COVID-19 pathology","volume":"61","author":"Bussani","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"eadd7197","DOI":"10.1126\/sciadv.add7197","article-title":"Nirmatrelvir-resistant SARS-CoV-2 variants with high fitness in an infectious cell culture system","volume":"8","author":"Zhou","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"105252","DOI":"10.1016\/j.antiviral.2022.105252","article-title":"Remdesivir, Molnupiravir and Nirmatrelvir remain active against SARS-CoV-2 Omicron and other variants of concern","volume":"198","author":"Vangeel","year":"2022","journal-title":"Antivir. Res."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Akinosoglou, K., Schinas, G., and Gogos, C. (2022). Oral antiviral treatment for COVID-19: A comprehensive review on nirmatrelvir\/ritonavir. Viruses, 14.","DOI":"10.3390\/v14112540"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1086\/375233","article-title":"A review of low-dose ritonavir in protease inhibitor combination therapy","volume":"36","author":"Cooper","year":"2003","journal-title":"Clin. Infect. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1046\/j.1365-2125.1997.00644.x","article-title":"Differential inhibition of cytochrome P450 isoforms by the protease inhibitors, ritonavir, saquinavir and indinavir","volume":"44","author":"Eagling","year":"1997","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"106634","DOI":"10.1016\/j.isci.2023.106634","article-title":"Cell culture systems for isolation of SARS-CoV-2 clinical isolates and generation of recombinant virus","volume":"26","author":"Chen","year":"2023","journal-title":"Iscience"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Bartak, M., B\u0105ska, P., Chodkowski, M., Tymi\u0144ska, B., Ba\u0144bura, M.W., and Cymerys, J. (2024). Neurons cytoskeletal architecture remodeling during the replication cycle of mouse coronavirus MHV-JHM: A morphological in vitro study. BMC Vet. Res., 20.","DOI":"10.1186\/s12917-023-03813-y"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Ferrandez-Pujante, A., Pons-Fuster, E., and L\u00f3pez-Jornet, P. (2022). Efficacy of photobiomodulation in reducing symptomatology and improving the quality of life in patients with xerostomia and hyposalivation: A randomized controlled trial. J. Clin. Med., 11.","DOI":"10.3390\/jcm11123414"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Jochems, P.G., Garssen, J., Van Keulen, A.M., Masereeuw, R., and Jeurink, P.V. (2018). Evaluating human intestinal cell lines for studying dietary protein absorption. Nutrients, 10.","DOI":"10.3390\/nu10030322"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e70613","DOI":"10.1002\/jmv.70613","article-title":"Circulating Microclots Are Structurally Associated With Neutrophil Extracellular Traps and Their Amounts Are Elevated in Long COVID Patients","volume":"97","author":"Thierry","year":"2025","journal-title":"J. Med. Virol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e00764-00724","DOI":"10.1128\/msphere.00764-24","article-title":"Circulating extracellular vesicles from severe COVID-19 patients induce lung inflammation","volume":"9","author":"Qian","year":"2024","journal-title":"mSphere"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Barbosa, M.S., de Lima, F., Peachazepi Moraes, C.R., Borba-Junior, I.T., Huber, S.C., Santos, I., Bombassaro, B., Dertkigil, S.S.J., Ilich, A., and Key, N.S. (2024). Angiopoietin2 is associated with coagulation activation and tissue factor expression in extracellular vesicles in COVID-19. Front. Med., 11.","DOI":"10.3389\/fmed.2024.1367544"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Caldera-Crespo, L.A., Paidas, M.J., Roy, S., Schulman, C.I., Kenyon, N.S., Daunert, S., and Jayakumar, A.R. (2022). Experimental models of COVID-19. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.792584"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.chom.2020.04.004","article-title":"An infectious cDNA clone of SARS-CoV-2","volume":"27","author":"Xie","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e2025866118","DOI":"10.1073\/pnas.2025866118","article-title":"Generation of SARS-CoV-2 reporter replicon for high-throughput antiviral screening and testing","volume":"118","author":"He","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1126\/science.abj8430","article-title":"Replication and single-cycle delivery of SARS-CoV-2 replicons","volume":"374","author":"Luna","year":"2021","journal-title":"Science"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Nguyen, H.T., Falzarano, D., Gerdts, V., and Liu, Q. (2021). Construction of a noninfectious SARS-CoV-2 replicon for antiviral-drug testing and gene function studies. J. Virol., 95.","DOI":"10.1128\/JVI.00687-21"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"24641","DOI":"10.3402\/jev.v3.24641","article-title":"Routes and mechanisms of extracellular vesicle uptake","volume":"3","author":"Mulcahy","year":"2014","journal-title":"J. Extracell. Vesicles"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e70017","DOI":"10.1002\/jex2.70017","article-title":"Mechanisms of extracellular vesicle uptake and implications for the design of cancer therapeutics","volume":"3","author":"Flemming","year":"2024","journal-title":"J. Extracell. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1002\/1873-3468.70055","article-title":"Interaction vesicles as emerging mediators of host-pathogen molecular crosstalk and their implications for infection dynamics","volume":"599","author":"Sabatke","year":"2025","journal-title":"FEBS Lett."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"16099","DOI":"10.1038\/s41598-020-73162-5","article-title":"Ultrastructural analysis of SARS-CoV-2 interactions with the host cell via high resolution scanning electron microscopy","volume":"10","author":"Caldas","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s00705-022-05366-1","article-title":"Virus interactions with the actin cytoskeleton\u2014What we know and do not know about SARS-CoV-2","volume":"167","author":"Kloc","year":"2022","journal-title":"Arch. Virol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Aminpour, M., Hameroff, S., and Tuszynski, J.A. (2022). How COVID-19 hijacks the cytoskeleton: Therapeutic implications. Life, 12.","DOI":"10.3390\/life12060814"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/j.chom.2020.11.003","article-title":"Integrative Imaging Reveals SARS-CoV-2-Induced Reshaping of Subcellular Morphologies","volume":"28","author":"Cortese","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"107384","DOI":"10.1016\/j.isci.2023.107384","article-title":"F-actin nanostructures rearrangements and regulation are essential for SARS-CoV-2 particle production in host pulmonary cells","volume":"26","author":"Swain","year":"2023","journal-title":"iScience"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/s41586-024-07817-y","article-title":"Molecular architecture of coronavirus double-membrane vesicle pore complex","volume":"633","author":"Huang","year":"2024","journal-title":"Nature"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e01385-25","DOI":"10.1128\/jvi.01385-25","article-title":"SARS-CoV-2 polyprotein expression and the induction of double-membrane vesicles","volume":"99","author":"Zhao","year":"2025","journal-title":"J. Virol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"eadq9580","DOI":"10.1126\/sciadv.adq9580","article-title":"A coronaviral pore-replicase complex links RNA synthesis and export from double-membrane vesicles","volume":"10","author":"Chen","year":"2024","journal-title":"Sci. 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