{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T02:24:42Z","timestamp":1781576682744,"version":"3.54.5"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2017,1,20]],"date-time":"2017-01-20T00:00:00Z","timestamp":1484870400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1U01CA187956"],"award-info":[{"award-number":["1U01CA187956"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1005241","type":"journal-article","created":{"date-parts":[[2017,1,20]],"date-time":"2017-01-20T18:29:01Z","timestamp":1484936941000},"page":"e1005241","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":36,"title":["Complex Dynamics of Virus Spread from Low Infection Multiplicities: Implications for the Spread of Oncolytic Viruses"],"prefix":"10.1371","volume":"13","author":[{"given":"Ignacio A.","family":"Rodriguez-Brenes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Hofacre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Wodarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2017,1,20]]},"reference":[{"key":"ref1","article-title":"Virus dynamics. Mathematical principles of immunology and virology","author":"MA Nowak","year":"2000"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/nri700","article-title":"Modelling viral and immune system dynamics","volume":"2","author":"AS Perelson","year":"2002","journal-title":"Nature Rev Immunol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/1741-7007-11-96","article-title":"Modeling the within-host dynamics of HIV infection","volume":"11","author":"AS Perelson","year":"2013","journal-title":"BMC Biol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"7518","DOI":"10.1128\/JVI.71.10.7518-7525.1997","article-title":"Viral dynamics of primary viremia and antiretroviral therapy in simian immunodeficiency virus infection","volume":"71","author":"MA Nowak","year":"1997","journal-title":"J Virol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1098\/rstb.1999.0422","article-title":"Genetic control and dynamics of the cellular immune response to the human T-cell leukaemia virus, HTLV-1","volume":"354","author":"CRM Bangham","year":"1999","journal-title":"Philosophical Transactions of the Royal Society, Series B"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"3928","DOI":"10.4049\/jimmunol.171.8.3928","article-title":"Different dynamics of CD4+ and CD8+ T cell responses during and after acute lymphocytic choriomeningitis virus infection","volume":"171","author":"RJ De Boer","year":"2003","journal-title":"J Immunol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1098\/rspb.2002.2097","article-title":"Procedures for reliable estimation of viral fitness from time-series data","volume":"269","author":"S Bonhoeffer","year":"2002","journal-title":"Proc Biol Sci"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"3384","DOI":"10.4049\/jimmunol.166.5.3384","article-title":"Depletion of CD4+ T cells precipitates immunopathology in immunodeficient mice infected with a noncytocidal virus","volume":"166","author":"JP Christensen","year":"2001","journal-title":"J Immunol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"9508","DOI":"10.1128\/JVI.71.12.9508-9514.1997","article-title":"The extent of early viral replication is a critical determinant of the natural history of simian immunodeficiency virus infection","volume":"71","author":"JD Lifson","year":"1997","journal-title":"J Virol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"10187","DOI":"10.1128\/JVI.75.21.10187-10199.2001","article-title":"Role of CD8(+) lymphocytes in control of simian immunodeficiency virus infection and resistance to rechallenge after transient early antiretroviral treatment","volume":"75","author":"JD Lifson","year":"2001","journal-title":"J Virol"},{"key":"ref11","first-page":"99","article-title":"Infectious Diseases","author":"AR McLean","year":"2013"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"e1002767","DOI":"10.1371\/journal.pcbi.1002767","article-title":"The role of exposure history on HIV acquisition: insights from repeated low-dose challenge studies","volume":"8","author":"RR Regoes","year":"2012","journal-title":"PLoS Comput Biol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1002\/hep.20882","article-title":"New kinetic models for the hepatitis C virus","volume":"42","author":"AS Perelson","year":"2005","journal-title":"Hepatology"},{"issue":"Suppl 1","key":"ref14","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1055\/s-2004-828673","article-title":"Hepatitis B virus kinetics and mathematical modeling","volume":"24","author":"AS Perelson","year":"2004","journal-title":"Semin Liver Dis"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/373117a0","article-title":"Viral Dynamics in Human-Immunodeficiency-Virus Type-1 Infection","volume":"373","author":"XP Wei","year":"1995","journal-title":"Nature"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/373123a0","article-title":"Rapid Turnover of Plasma Virions and Cd4 Lymphocytes in Hiv-1 Infection","volume":"373","author":"DD Ho","year":"1995","journal-title":"Nature"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1126\/science.271.5255.1582","article-title":"Hiv-1 Dynamics in-Vivo\u2014Virion Clearance Rate, Infected Cell Life- Span, and Viral Generation Time","volume":"271","author":"AS Perelson","year":"1996","journal-title":"Science"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1084\/jem.190.6.841","article-title":"Viral dynamics of acute HIV-1 infection","volume":"190","author":"SJ Little","year":"1999","journal-title":"J Exp Med"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"6096","DOI":"10.1128\/JVI.00127-10","article-title":"Estimation of the initial viral growth rate and basic reproductive number during acute HIV-1 infection","volume":"84","author":"RM Ribeiro","year":"2010","journal-title":"J Virol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.virol.2011.11.014","article-title":"Early infection and spread of a conditionally replicating adenovirus under conditions of plaque formation","volume":"423","author":"A Hofacre","year":"2012","journal-title":"Virology"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"e1002547","DOI":"10.1371\/journal.pcbi.1002547","article-title":"Complex spatial dynamics of oncolytic viruses in vitro: mathematical and experimental approaches","volume":"8","author":"D Wodarz","year":"2012","journal-title":"PLoS Comput Biol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S1535-6108(03)00170-3","article-title":"Getting oncolytic virus therapies off the ground","volume":"4","author":"JC Bell","year":"2003","journal-title":"Cancer Cell"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"S157","DOI":"10.4161\/cbt.216","article-title":"Cancer-specific viruses and the development of ONYX-015","volume":"2","author":"F McCormick","year":"2003","journal-title":"Cancer Biol Ther"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/nrclinonc.2015.106","article-title":"Skin cancer: T-VEC oncolytic viral therapy shows promise in melanoma","volume":"12","author":"D Killock","year":"2015","journal-title":"Nat Rev Clin Oncol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.chom.2012.05.005","article-title":"Adenovirus evasion of interferon-mediated innate immunity by direct antagonism of a cellular histone posttranslational modification","volume":"11","author":"GJ Fonseca","year":"2012","journal-title":"Cell Host Microbe"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"6969","DOI":"10.1093\/emboj\/20.24.6969","article-title":"Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells","volume":"20","author":"M Gottlicher","year":"2001","journal-title":"EMBO J"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"4566","DOI":"10.1128\/JVI.05545-11","article-title":"The histone deacetylase inhibitor valproic acid lessens NK cell action against oncolytic virus-infected glioblastoma cells by inhibition of STAT5\/T-BET signaling and generation of gamma interferon","volume":"86","author":"CA Alvarez-Breckenridge","year":"2012","journal-title":"J Virol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1007\/s00018-007-7079-x","article-title":"The mechanisms of action of valproate in neuropsychiatric disorders: can we see the forest for the trees?","volume":"64","author":"G Rosenberg","year":"2007","journal-title":"Cell Mol Life Sci"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1038\/ni.1645","article-title":"Toll-like receptor-mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI(3)K-mTOR-p70S6K pathway","volume":"9","author":"W Cao","year":"2008","journal-title":"Nat Immunol"},{"key":"ref30","first-page":"329","article-title":"Animal cell technology meets genomics","author":"TB Ferreira","year":"2005"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1002\/jnr.490390417","article-title":"Adenovirus-mediated gene therapy of experimental gliomas","volume":"39","author":"M Perez-Cruet","year":"1994","journal-title":"Journal of neuroscience research"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1023\/A:1021106116887","article-title":"Rapid titration of adenoviral infectivity by flow cytometry in batch culture of infected HEK293 cells","volume":"38","author":"V Gueret","year":"2002","journal-title":"Cytotechnology"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"9470","DOI":"10.1128\/JVI.72.12.9470-9478.1998","article-title":"Replication of ONYX-015, a potential anticancer adenovirus, is independent of p53 status in tumor cells","volume":"72","author":"T Rothmann","year":"1998","journal-title":"Journal of virology"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.biotechadv.2008.10.003","article-title":"From the first to the third generation adenoviral vector: what parameters are governing the production yield?","volume":"27","author":"E Dormond","year":"2009","journal-title":"Biotechnology advances"},{"key":"ref35","article-title":"Current Biology","author":"CA Janeway","year":"1997"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1098\/rsif.2006.0136","article-title":"Modelling dynamics of the type I interferon response to in vitro viral infection","volume":"3","author":"TJ Howat","year":"2006","journal-title":"Journal of The Royal Society Interface"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1021\/j100540a008","article-title":"Exact Stochastic Simulation of Coupled Chemical-Reactions","volume":"81","author":"DT Gillespie","year":"1977","journal-title":"Journal of Physical Chemistry"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"e1001085","DOI":"10.1371\/journal.pcbi.1001085","article-title":"A dynamical systems model for combinatorial cancer therapy enhances oncolytic adenovirus efficacy by MEK-inhibition","volume":"7","author":"N Bagheri","year":"2011","journal-title":"PLoS Comput Biol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1073\/pnas.66.4.1052","article-title":"Interferon and cell division, I. inhibition of the multiplication of mouse leukemia L 1210 cells in vitro by interferon preparations","volume":"66","author":"I Gresser","year":"1970","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.3181\/00379727-138-36047","article-title":"Interferon and Cell Division VI. Inhibitory Effect of Interferon on the Multiplication of Mouse Embryo and Mouse Kidney Cells in Primary Cultures","volume":"138","author":"P Lindahl-Magnusson","year":"1971","journal-title":"Experimental Biology and Medicine"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/0014-4827(79)90450-6","article-title":"Interferon effects on the growth and division of human fibroblasts","volume":"121","author":"LM Pfeffer","year":"1979","journal-title":"Experimental cell research"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1038\/274798a0","article-title":"Interferon affects both G1 and S&amp;plus; G2 in cells stimulated from quiescence to growth","volume":"274","author":"F Balkwill","year":"1978","journal-title":"Nature"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1063\/1.1378322","article-title":"Approximate accelerated stochastic simulation of chemically reacting systems","volume":"115","author":"DT Gillespie","year":"2001","journal-title":"Journal of Chemical Physics"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.coviro.2015.03.007","article-title":"MicroRNAs and oncolytic viruses","volume":"13","author":"AJ Ruiz","year":"2015","journal-title":"Curr Opin Virol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"e73759","DOI":"10.1371\/journal.pone.0073759","article-title":"Mathematical model for radial expansion and conflation of intratumoral infectious centers predicts curative oncolytic virotherapy parameters","volume":"8","author":"K Bailey","year":"2013","journal-title":"PLoS One"},{"key":"ref46","first-page":"3501","article-title":"Viruses as antitumor weapons: defining conditions for tumor remission","volume":"61","author":"D Wodarz","year":"2001","journal-title":"Cancer Res"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.mbs.2005.11.001","article-title":"Mathematical modeling of cancer radiovirotherapy","volume":"199","author":"D Dingli","year":"2006","journal-title":"Math Biosci"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1038\/cgt.2009.40","article-title":"Dynamics of multiple myeloma tumor therapy with a recombinant measles virus","volume":"16","author":"D Dingli","year":"2009","journal-title":"Cancer Gene Ther"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1745-6150-1-6","article-title":"Mathematical modeling of tumor therapy with oncolytic viruses: regimes with complete tumor elimination within the framework of deterministic models","volume":"1","author":"AS Novozhilov","year":"2006","journal-title":"Biol Direct"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1089\/hum.2009.143","article-title":"Interference of CD40L-mediated tumor immunotherapy by oncolytic vesicular stomatitis virus","volume":"21","author":"F Galivo","year":"2010","journal-title":"Hum Gene Ther"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/cgt.2013.55","article-title":"Overcoming cancer cell resistance to VSV oncolysis with JAK1\/2 inhibitors","volume":"20","author":"D Escobar-Zarate","year":"2013","journal-title":"Cancer Gene Ther"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1128\/JVI.80.1.332-341.2006","article-title":"In vivo and in vitro analysis of factor binding sites in Jaagsiekte sheep retrovirus long terminal repeat enhancer sequences: roles of HNF-3, NF-I, and C\/EBP for activity in lung epithelial cells","volume":"80","author":"K McGee-Estrada","year":"2006","journal-title":"J Virol"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1005548","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2017,5,19]],"date-time":"2017-05-19T00:00:00Z","timestamp":1495152000000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1005241","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T08:15:12Z","timestamp":1601367312000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1005241"}},"subtitle":[],"editor":[{"given":"Roland R","family":"Regoes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,1,20]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,1,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1005241","relation":{"correction":[{"id-type":"doi","id":"10.1371\/journal.pcbi.1005548","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1,20]]}}}