{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T06:21:52Z","timestamp":1783578112047,"version":"3.55.0"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Epstein-Barr virus (EBV) infects greater than 90% of humans benignly for life but can be associated with tumors. It is a uniquely human pathogen that is amenable to quantitative analysis; however, there is no applicable animal model. Computer models may provide a virtual environment to perform experiments not possible in human volunteers.<\/jats:p><jats:p>Results: We report the application of a relatively simple stochastic cellular automaton (C-ImmSim) to the modeling of EBV infection. Infected B-cell dynamics in the acute and chronic phases of infection correspond well to clinical data including the establishment of a long term persistent infection (up to 10 years) that is absolutely dependent on access of latently infected B cells to the peripheral pool where they are not subject to immunosurveillance. In the absence of this compartment the infection is cleared.<\/jats:p><jats:p>Availability: The latest version 6 of C-ImmSim is available under the GNU General Public License and is downloadable from www.iac.cnr.it\/~filippo\/cimmsim.html<\/jats:p><jats:p>Contact: david.thorley-lawson@tufts.edu<\/jats:p>","DOI":"10.1093\/bioinformatics\/btm044","type":"journal-article","created":{"date-parts":[[2007,3,7]],"date-time":"2007-03-07T03:01:32Z","timestamp":1173236492000},"page":"1371-1377","source":"Crossref","is-referenced-by-count":78,"title":["Simulating Epstein-Barr virus infection with C-ImmSim"],"prefix":"10.1093","volume":"23","author":[{"given":"Filippo","family":"Castiglione","sequence":"first","affiliation":[{"name":"1 Istituto Applicazioni del Calcolo (IAC) \u201cM. Picone\u201d-CNR, Viale del Policlinico, 137, 00161 \u2013 Rome, Italy, 2Virginia Bioinformatics Institute, Washington St., MC 0477, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 and 3Department of Pathology Jaharis Building, Tufts University School of Medicine, 150 Harrison Ave., Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Duca","sequence":"additional","affiliation":[{"name":"1 Istituto Applicazioni del Calcolo (IAC) \u201cM. Picone\u201d-CNR, Viale del Policlinico, 137, 00161 \u2013 Rome, Italy, 2Virginia Bioinformatics Institute, Washington St., MC 0477, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 and 3Department of Pathology Jaharis Building, Tufts University School of Medicine, 150 Harrison Ave., Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul","family":"Jarrah","sequence":"additional","affiliation":[{"name":"1 Istituto Applicazioni del Calcolo (IAC) \u201cM. Picone\u201d-CNR, Viale del Policlinico, 137, 00161 \u2013 Rome, Italy, 2Virginia Bioinformatics Institute, Washington St., MC 0477, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 and 3Department of Pathology Jaharis Building, Tufts University School of Medicine, 150 Harrison Ave., Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Laubenbacher","sequence":"additional","affiliation":[{"name":"1 Istituto Applicazioni del Calcolo (IAC) \u201cM. Picone\u201d-CNR, Viale del Policlinico, 137, 00161 \u2013 Rome, Italy, 2Virginia Bioinformatics Institute, Washington St., MC 0477, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 and 3Department of Pathology Jaharis Building, Tufts University School of Medicine, 150 Harrison Ave., Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"Hochberg","sequence":"additional","affiliation":[{"name":"1 Istituto Applicazioni del Calcolo (IAC) \u201cM. Picone\u201d-CNR, Viale del Policlinico, 137, 00161 \u2013 Rome, Italy, 2Virginia Bioinformatics Institute, Washington St., MC 0477, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 and 3Department of Pathology Jaharis Building, Tufts University School of Medicine, 150 Harrison Ave., Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Thorley-Lawson","sequence":"additional","affiliation":[{"name":"1 Istituto Applicazioni del Calcolo (IAC) \u201cM. Picone\u201d-CNR, Viale del Policlinico, 137, 00161 \u2013 Rome, Italy, 2Virginia Bioinformatics Institute, Washington St., MC 0477, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 and 3Department of Pathology Jaharis Building, Tufts University School of Medicine, 150 Harrison Ave., Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,3,6]]},"reference":[{"key":"2023041104583641100_","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/S1074-7613(00)80622-6","article-title":"EBV persistence in memory B cells in vivo","volume":"9","author":"Babcock","year":"1998","journal-title":"Immunity"},{"key":"2023041104583641100_","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S1074-7613(00)00049-2","article-title":"The expression pattern of Epstein-Barr virus latent genes in vivo is dependent upon the differentiation stage of the infected B cell","volume":"13","author":"Babcock","year":"2000","journal-title":"Immunity"},{"key":"2023041104583641100_","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S0010-4825(01)00011-7","article-title":"Design and implementation of an immune system simulator","volume":"31","author":"Bernaschi","year":"2001","journal-title":"Comput. Biol. Med."},{"key":"2023041104583641100_","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/0167-5699(92)90135-T","article-title":"A computer model of cellular interactions in the immune system","volume":"13","author":"Celada","year":"1992","journal-title":"Immunol. Today"},{"key":"2023041104583641100_","doi-asserted-by":"crossref","first-page":"3309","DOI":"10.4049\/jimmunol.168.7.3309","article-title":"Clonal selection, clonal senescence, and clonal succession: the evolution of the T cell response to infection with a persistent virus","volume":"168","author":"Davenport","year":"2002","journal-title":"J. Immunol."},{"key":"2023041104583641100_","volume-title":"Kuby Immunology.","author":"Goldsby","year":"2000"},{"key":"2023041104583641100_","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.2105\/AJPH.54.10.1699","article-title":"The incubation period of Infectious Mononucleosis","volume":"54","author":"Hoagland","year":"1964","journal-title":"Am. J. Public Health"},{"key":"2023041104583641100_","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1073\/pnas.2237267100","article-title":"Demonstration of the Burkitt's lymphoma Epstein-Barr virus phenotype in dividing latently infected memory cells in vivo","volume":"101","author":"Hochberg","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023041104583641100_","doi-asserted-by":"crossref","first-page":"5194","DOI":"10.1128\/JVI.78.10.5194-5204.2004","article-title":"Acute infection with Epstein-Barr virus targets and overwhelms the peripheral memory B-cell compartment with resting, latently infected cells","volume":"78","author":"Hochberg","year":"2004","journal-title":"J. Virol."},{"key":"2023041104583641100_","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1128\/JVI.79.2.1296-1307.2005","article-title":"Terminal differentiation into plasma cells initiates the replicative cycle of Epstein-Barr virus in vivo","volume":"79","author":"Laichalk","year":"2005","journal-title":"J. Virol."},{"key":"2023041104583641100_","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1006\/smim.1998.0143","article-title":"An innate sense of danger","volume":"10","author":"Matzinger","year":"1998","journal-title":"Semin. Immunol."},{"key":"2023041104583641100_","doi-asserted-by":"crossref","first-page":"4882","DOI":"10.1128\/jvi.71.7.4882-4891.1997","article-title":"Identification of the site of Epstein-Barr virus persistence in vivo as a resting B cell","volume":"71","author":"Miyashita","year":"1997","journal-title":"J. Virol."},{"key":"2023041104583641100_","first-page":"2575","article-title":"Epstein-Barr virus","volume-title":"Virology.","author":"Rickinson","year":"2001"},{"key":"2023041104583641100_","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S0022-5193(05)80737-4","article-title":"A model for simulating cognate recognition and response in the immune system","volume":"158","author":"Seiden","year":"1992","journal-title":"J. Theor. Biol."},{"key":"2023041104583641100_","first-page":"970","article-title":"Epstein-Barr virus","volume-title":"Sampter's Immunologic Diseases.","author":"Thorley-Lawson","year":"2001"},{"key":"2023041104583641100_","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/35095584","article-title":"Epstein-Barr virus: exploiting the immune system","volume":"1","author":"Thorley-Lawson","year":"2001","journal-title":"Nat. Rev. Immunol."},{"key":"2023041104583641100_","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1016\/S0024-3205(99)00214-3","article-title":"A model for persistent infection with Epstein-Barr virus: the stealth virus of human B cells","volume":"65","author":"Thorley-Lawson","year":"1999","journal-title":"Life Sci."},{"key":"2023041104583641100_","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1056\/NEJMra032015","article-title":"Persistence of the Epstein-Barr virus and the origins of associated lymphomas","volume":"350","author":"Thorley-Lawson","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"2023041104583641100_","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1002\/jmv.10522","article-title":"Mathematical model to simulate the cellular dynamics of infection with human herpesvirus-6 in EBV-negative infectious mononucleosis","volume":"71","author":"Wang","year":"2003","journal-title":"J. Med. Virol."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/23\/11\/1371\/49812811\/bioinformatics_23_11_1371.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/23\/11\/1371\/49812811\/bioinformatics_23_11_1371.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T21:54:13Z","timestamp":1683755653000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/23\/11\/1371\/199949"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,3,6]]},"references-count":19,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2007,6,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btm044","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2007,6]]},"published":{"date-parts":[[2007,3,6]]}}}