{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T13:35:24Z","timestamp":1781789724102,"version":"3.54.5"},"reference-count":64,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T00:00:00Z","timestamp":1685491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"NIH","doi-asserted-by":"publisher","award":["AI139088"],"award-info":[{"award-number":["AI139088"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIH","doi-asserted-by":"publisher","award":["AI125324"],"award-info":[{"award-number":["AI125324"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIH","doi-asserted-by":"publisher","award":["P20GM104420"],"award-info":[{"award-number":["P20GM104420"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Respiratory viral infections are a leading global cause of disease with multiple viruses detected in 20\u201330% of cases, and several viruses simultaneously circulating. Some infections with unique viral copathogens result in reduced pathogenicity, while other viral pairings can worsen disease. The mechanisms driving these dichotomous outcomes are likely variable and have only begun to be examined in the laboratory and clinic. To better understand viral\u2013viral coinfections and predict potential mechanisms that result in distinct disease outcomes, we first systematically fit mathematical models to viral load data from ferrets infected with respiratory syncytial virus (RSV), followed by influenza A virus (IAV) after 3 days. The results suggest that IAV reduced the rate of RSV production, while RSV reduced the rate of IAV infected cell clearance. We then explored the realm of possible dynamics for scenarios that had not been examined experimentally, including a different infection order, coinfection timing, interaction mechanisms, and viral pairings. IAV coinfection with rhinovirus (RV) or SARS-CoV-2 (CoV2) was examined by using human viral load data from single infections together with murine weight-loss data from IAV-RV, RV-IAV, and IAV-CoV2 coinfections to guide the interpretation of the model results. Similar to the results with RSV-IAV coinfection, this analysis shows that the increased disease severity observed during murine IAV-RV or IAV-CoV2 coinfection was likely due to the slower clearance of IAV-infected cells by the other viruses. The improved outcome when IAV followed RV, on the other hand, could be replicated when the rate of RV infected cell clearance was reduced by IAV. Simulating viral\u2013viral coinfections in this way provides new insights about how viral\u2013viral interactions can regulate disease severity during coinfection and yields testable hypotheses ripe for experimental evaluation.<\/jats:p>","DOI":"10.3390\/v15061303","type":"journal-article","created":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T01:40:56Z","timestamp":1685583656000},"page":"1303","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["How Interactions during Viral\u2013Viral Coinfection Can Shape Infection Kinetics"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6826-3753","authenticated-orcid":false,"given":"Lubna","family":"Pinky","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph R.","family":"DeAguero","sequence":"additional","affiliation":[{"name":"Bioinformatics and Computational Biology Program, University of Idaho, Moscow, ID 83844, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher H.","family":"Remien","sequence":"additional","affiliation":[{"name":"Department of Mathematics and Statistical Science, University of Idaho, Moscow, ID 83844, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7092-6904","authenticated-orcid":false,"given":"Amber M.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"27142","DOI":"10.1073\/pnas.1911083116","article-title":"Virus\u2013virus interactions impact the population dynamics of influenza and the common cold","volume":"116","author":"Nickbakhsh","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1002\/jmv.25953","article-title":"Coinfection in SARS-CoV-2 infected patients: Where are influenza virus and rhinovirus\/enterovirus?","volume":"92","author":"Nowak","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.anpedi.2020.12.024","article-title":"Coinfections of influenza and other respiratory viruses are associated to children","volume":"96","author":"Sanz","year":"2022","journal-title":"An. Pediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"86","DOI":"10.4168\/aard.2019.7.2.86","article-title":"Comparison of clinical severity between single-and coinfections of respiratory syncytial virus and influenza virus with common respiratory viruses","volume":"7","author":"Park","year":"2019","journal-title":"Allergy Asthma Respir. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1093\/infdis\/jix641","article-title":"Etiology and impact of coinfections in children hospitalized with community-acquired pneumonia","volume":"218","author":"Nolan","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Pacheco, G.A., G\u00e1lvez, N., Soto, J.A., Andrade, C.A., and Kalergis, A.M. (2021). Bacterial and Viral Coinfections with the Human Respiratory Syncytial Virus. Microorganisms, 9.","DOI":"10.3390\/microorganisms9061293"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.cmi.2020.08.012","article-title":"Co-infection with other respiratory pathogens in COVID-19 patients","volume":"27","author":"Calcagno","year":"2021","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11908-020-0711-8","article-title":"Respiratory virus co-infection in acute respiratory infections in children","volume":"22","author":"Meskill","year":"2020","journal-title":"Curr. Infect. Dis. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1002\/jmv.26817","article-title":"Co-infection of influenza A virus and SARS-CoV-2: A retrospective cohort study","volume":"93","author":"Cheng","year":"2021","journal-title":"J. Med. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1111\/apa.12440","article-title":"Children with multiple viral respiratory infections are older than those with single viruses","volume":"103","author":"Eriksson","year":"2014","journal-title":"Acta Paediatr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2815","DOI":"10.1007\/s00604-017-2300-6","article-title":"Simultaneous detection of multiple viruses in their coinfected cells using multicolour imaging with self-assembled quantum dot probes","volume":"184","author":"Fayyadh","year":"2017","journal-title":"Microchim. Acta"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1128\/JCM.03298-14","article-title":"Clinical relevance of multiple respiratory virus detection in adult patients with acute respiratory illness","volume":"53","author":"Choi","year":"2015","journal-title":"J. Clin. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1056\/NEJMoa1405870","article-title":"Community-acquired pneumonia requiring hospitalization among US children","volume":"372","author":"Jain","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1056\/NEJMoa1500245","article-title":"Community-acquired pneumonia requiring hospitalization among US adults","volume":"373","author":"Jain","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_15","first-page":"363","article-title":"Single and multiple respiratory virus infections and severity of respiratory disease: A systematic review","volume":"15","author":"Goka","year":"2014","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1111\/j.1750-2659.2011.00265.x","article-title":"Multiple vs. single virus respiratory infections: Viral load and clinical disease severity in hospitalized children","volume":"6","author":"Martin","year":"2012","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1097\/01.inf.0000168741.59747.2d","article-title":"Single vs. dual respiratory virus infections in hospitalized infants: Impact on clinical course of disease and interferon-\u03b3 response","volume":"24","author":"Aberle","year":"2005","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_18","unstructured":"Stefanska, I., Romanowska, M., Donevski, S., Gawryluk, D., and Brydak, L.B. (2013). Respiratory Regulation\u2014The Molecular Approach, Springer."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jcv.2016.04.019","article-title":"Respiratory viral coinfection and disease severity in children: A systematic review and meta-analysis","volume":"80","author":"Scotta","year":"2016","journal-title":"J. Clin. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.jcv.2009.03.008","article-title":"Do rhinoviruses reduce the probability of viral co-detection during acute respiratory tract infections?","volume":"45","author":"Greer","year":"2009","journal-title":"J. Clin. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Cebey-L\u00f3pez, M., Herberg, J., Pardo-Seco, J., G\u00f3mez-Carballa, A., Martin\u00f3n-Torres, N., Salas, A., Martin\u00f3n-S\u00e1nchez, J.M., Gormley, S., Sumner, E., and Fink, C. (2015). Viral co-infections in pediatric patients hospitalized with lower tract acute respiratory infections. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0136526"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1002\/jmv.25499","article-title":"Clinical characteristics of the lower respiratory tract infection caused by a single infection or coinfection of the human parainfluenza virus in children","volume":"91","author":"Zhong","year":"2019","journal-title":"J. Med. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1111\/irv.12020","article-title":"Influenza A viruses dual and multiple infections with other respiratory viruses and risk of hospitalization and mortality","volume":"7","author":"Goka","year":"2013","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zhang, G., Hu, Y., Wang, H., Zhang, L., Bao, Y., and Zhou, X. (2012). High incidence of multiple viral infections identified in upper respiratory tract infected children under three years of age in Shanghai, China. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0044568"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1002\/ppul.21552","article-title":"Infection with multiple viruses is not associated with increased disease severity in children with bronchiolitis","volume":"47","author":"Brand","year":"2012","journal-title":"Pediatr. Pulmonol."},{"key":"ref_26","first-page":"91","article-title":"In vitro growth profiles of respiratory syncytial virus in the presence of influenza virus","volume":"44","author":"Shinjoh","year":"2000","journal-title":"Acta Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1093\/infdis\/jiy184","article-title":"Investigating viral interference between influenza A virus and human respiratory syncytial virus in a ferret model of infection","volume":"218","author":"Chan","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_28","first-page":"1","article-title":"Interferon-dependent and respiratory virus-specific interference in dual infections of airway epithelia","volume":"10","author":"Geiser","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Drori, Y., Jacob-Hirsch, J., Pando, R., Glatman-Freedman, A., Friedman, N., Mendelson, E., and Mandelboim, M. (2020). Influenza A virus inhibits RSV infection via a two-wave expression of IFIT proteins. Viruses, 12.","DOI":"10.3390\/v12101171"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"720","DOI":"10.4049\/jimmunol.2000751","article-title":"Respiratory Syncytial Virus Provides Protection against a Subsequent Influenza A Virus Infection","volume":"208","author":"Hartwig","year":"2022","journal-title":"J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1038\/s41564-022-01242-5","article-title":"Coinfection by influenza A virus and respiratory syncytial virus produces hybrid virus particles","volume":"7","author":"Haney","year":"2022","journal-title":"Nat. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s00430-015-0441-y","article-title":"Enhanced growth of influenza A virus by coinfection with human parainfluenza virus type 2","volume":"205","author":"Goto","year":"2016","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e00881-18","DOI":"10.1128\/JVI.00881-18","article-title":"Attenuation of influenza A virus disease severity by viral coinfection in a mouse model","volume":"92","author":"Gonzalez","year":"2018","journal-title":"J. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e254","DOI":"10.1016\/S2666-5247(20)30114-2","article-title":"Interference between rhinovirus and influenza A virus: A clinical data analysis and experimental infection study","volume":"1","author":"Wu","year":"2020","journal-title":"Lancet Microbe"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e00479-21","DOI":"10.1128\/mSphere.00479-21","article-title":"Rhinovirus reduces the severity of subsequent respiratory viral infections by interferon-dependent and-independent mechanisms","volume":"6","author":"Gonzalez","year":"2021","journal-title":"Msphere"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Geiser, J., Boivin, G., Huang, S., Constant, S., Kaiser, L., Tapparel, C., and Essaidi-Laziosi, M. (2021). RSV and HMPV Infections in 3D Tissue Cultures: Mechanisms Involved in Virus-Host and Virus-Virus Interactions. Viruses, 13.","DOI":"10.3390\/v13010139"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Clark, J.J., Penrice-Randal, R., Sharma, P., Kipar, A., Dong, X., Davidson, A.D., Williamson, M.K., Matthews, D.A., Turtle, L., and Prince, T. (2020). Sequential infection with influenza A virus followed by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to more severe disease and encephalitis in a mouse model of COVID-19. bioRxiv, in press.","DOI":"10.1101\/2020.10.13.334532"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e0179121","DOI":"10.1128\/jvi.01791-21","article-title":"SARS-CoV-2 and Influenza A virus Co-infections in Ferrets","volume":"96","author":"Huang","year":"2022","journal-title":"J. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e978","DOI":"10.1093\/cid\/ciaa1747","article-title":"Coinfection by Severe Acute Respiratory Syndrome Coronavirus 2 and Influenza A (H1N1) pdm09 Virus Enhances the Severity of Pneumonia in Golden Syrian Hamsters","volume":"72","author":"Zhang","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_40","first-page":"1","article-title":"Sequential infection with H1N1 and SARS-CoV-2 aggravated COVID-19 pathogenesis in a mammalian model, and co-vaccination as an effective method of prevention of COVID-19 and influenza","volume":"6","author":"Bao","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/s41422-021-00473-1","article-title":"Coinfection with influenza A virus enhances SARS-CoV-2 infectivity","volume":"31","author":"Bai","year":"2021","journal-title":"Cell Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5819","DOI":"10.1038\/s41467-021-26113-1","article-title":"Increased lethality in influenza and SARS-CoV-2 coinfection is prevented by influenza immunity but not SARS-CoV-2 immunity","volume":"12","author":"Achdout","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Fage, C., H\u00e9naut, M., Carbonneau, J., Piret, J., and Boivin, G. (2022). Influenza A (H1N1) pdm09 Virus but Not Respiratory Syncytial Virus Interferes with SARS-CoV-2 Replication during Sequential Infections in Human Nasal Epithelial Cells. Viruses, 14.","DOI":"10.3390\/v14020395"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1093\/infdis\/jiab147","article-title":"Human rhinovirus infection blocks severe acute respiratory syndrome coronavirus 2 replication within the respiratory epithelium: Implications for COVID-19 epidemiology","volume":"224","author":"Dee","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/imr.12692","article-title":"Host-pathogen kinetics during influenza infection and coinfection: Insights from predictive modeling","volume":"285","author":"Smith","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Pinky, L., and Dobrovolny, H.M. (2016). Coinfections of the respiratory tract: Viral competition for resources. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0155589"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e68864","DOI":"10.7554\/eLife.68864","article-title":"Dynamically linking influenza virus infection with lung injury to predict disease severity","volume":"10","author":"Myers","year":"2021","journal-title":"eLife"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"xtac022","DOI":"10.1093\/femsmc\/xtac022","article-title":"Increased virus dissemination leads to enhanced lung injury but not inflammation during influenza-associated secondary bacterial infection","volume":"3","author":"Smith","year":"2022","journal-title":"FEMS Microbes"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1128\/iai.29.2.348-355.1980","article-title":"Evaluation of influenza A\/Hong Kong\/123\/77 (H1N1) ts-1A2 and cold-adapted recombinant viruses in seronegative adult volunteers","volume":"29","author":"Murphy","year":"1980","journal-title":"Infect. Immun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.jcv.2004.02.011","article-title":"Viral titers in nasal lining fluid compared to viral titers in nasal washes during experimental rhinovirus infection","volume":"30","author":"Hendley","year":"2004","journal-title":"J. Clin. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/s41586-020-2196-x","article-title":"Virological assessment of hospitalized patients with COVID-2019","volume":"581","author":"Corman","year":"2020","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1002\/wsbm.129","article-title":"Influenza A virus infection kinetics: Quantitative data and models","volume":"3","author":"Smith","year":"2011","journal-title":"Wiley Interdiscip. Rev. Syst. Biol. Med."},{"key":"ref_53","first-page":"1","article-title":"Sialic acid receptors of viruses","volume":"367","author":"Matrosovich","year":"2015","journal-title":"Top. Curr. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1038\/s41385-020-00340-z","article-title":"Animal and translational models of SARS-CoV-2 infection and COVID-19","volume":"13","author":"Johansen","year":"2020","journal-title":"Mucosal Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s10719-006-5442-z","article-title":"Human trachea primary epithelial cells express both sialyl (\u03b12-3) Gal receptor for human parainfluenza virus type 1 and avian influenza viruses, and sialyl (\u03b12-6) Gal receptor for human influenza viruses","volume":"23","author":"Kogure","year":"2006","journal-title":"Glycoconj. J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"452","DOI":"10.3389\/fimmu.2019.00452","article-title":"Contribution of cytokines to tissue damage during human respiratory syncytial virus infection","volume":"10","author":"Bohmwald","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/440435a","article-title":"Influenza virus receptors in the human airway","volume":"440","author":"Shinya","year":"2006","journal-title":"Nature"},{"key":"ref_58","unstructured":"Antony, F. (2023, May 28). Monolix Version 2019R1. Available online: http:\/\/lixoft.com\/products\/monolix\/."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.3389\/fmicb.2018.01554","article-title":"Influenza virus infection model with density dependence supports biphasic viral decay","volume":"9","author":"Smith","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Pinky, L., Burke, C.W., Russell, C.J., and Smith, A.M. (2021). Quantifying dose-, strain-, and tissue-specific kinetics of parainfluenza virus infection. PLoS Comput. Biol., 17.","DOI":"10.1371\/journal.pcbi.1009299"},{"key":"ref_61","unstructured":"Akaike, H. (1998). Selected Papers of Hirotugu Akaike, Springer."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"10786","DOI":"10.1128\/JVI.01432-15","article-title":"Increased immune response variability during simultaneous viral coinfection leads to unpredictability in CD8 T cell immunity and pathogenesis","volume":"89","author":"Kenney","year":"2015","journal-title":"J. Virol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1007\/s00285-009-0281-8","article-title":"An accurate two-phase approximate solution to an acute viral infection model","volume":"60","author":"Smith","year":"2010","journal-title":"J. Math. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.coisb.2018.10.005","article-title":"Validated models of immune response to virus infection","volume":"12","author":"Smith","year":"2018","journal-title":"Curr. Opin. Syst. Biol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/6\/1303\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:46:26Z","timestamp":1760125586000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/6\/1303"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,31]]},"references-count":64,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["v15061303"],"URL":"https:\/\/doi.org\/10.3390\/v15061303","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,31]]}}}