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Development of targeted antivirals has been hampered by the lack of robust HCV cell culture systems that reliably predict human responses. Here, we show the entire HCV life cycle recapitulated in micropatterned cocultures (MPCCs) of primary human hepatocytes and supportive stroma in a multiwell format. MPCCs form polarized cell layers expressing all known HCV entry factors and sustain viral replication for several weeks. When coupled with highly sensitive fluorescence- and luminescence-based reporter systems, MPCCs have potential as a high-throughput platform for simultaneous assessment of in vitro efficacy and toxicity profiles of anti-HCV therapeutics.<\/jats:p>","DOI":"10.1073\/pnas.0915130107","type":"journal-article","created":{"date-parts":[[2010,2,1]],"date-time":"2010-02-01T22:51:30Z","timestamp":1265064690000},"page":"3141-3145","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":203,"title":["Persistent hepatitis C virus infection in microscale primary human hepatocyte cultures"],"prefix":"10.1073","volume":"107","author":[{"given":"Alexander","family":"Ploss","sequence":"first","affiliation":[{"name":"Center for the Study of Hepatitis C and"},{"name":"Laboratory of Virology and Infectious Diseases, The Rockefeller University, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salman R.","family":"Khetani","sequence":"additional","affiliation":[{"name":"Division of Health Sciences and Technology, Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher T.","family":"Jones","sequence":"additional","affiliation":[{"name":"Center for the Study of Hepatitis C and"},{"name":"Laboratory of Virology and Infectious Diseases, The Rockefeller University, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Syder","sequence":"additional","affiliation":[{"name":"Center for the Study of Hepatitis C and"},{"name":"Laboratory of Virology and Infectious Diseases, The Rockefeller University, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kartik","family":"Trehan","sequence":"additional","affiliation":[{"name":"Division of Health Sciences and Technology, Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeriya A.","family":"Gaysinskaya","sequence":"additional","affiliation":[{"name":"Center for the Study of Hepatitis C and"},{"name":"Laboratory of Virology and Infectious Diseases, The Rockefeller University, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"Mu","sequence":"additional","affiliation":[{"name":"Center for the Study of Hepatitis C and"},{"name":"Laboratory of Virology and Infectious Diseases, The Rockefeller University, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Ritola","sequence":"additional","affiliation":[{"name":"Center for the Study of Hepatitis C and"},{"name":"Laboratory of Virology and Infectious Diseases, The Rockefeller University, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles M.","family":"Rice","sequence":"additional","affiliation":[{"name":"Center for the Study of Hepatitis C and"},{"name":"Laboratory of Virology and Infectious Diseases, The Rockefeller University, New York, NY 10065;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangeeta N.","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Division of Health Sciences and Technology, Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Howard Hughes Medical Institute, Cambridge, MA 02139; and"},{"name":"Division of Medicine, Brigham and Women\u2019s Hospital, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,2]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2006.10.005"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/14.5.987"},{"key":"e_1_3_3_3_2","first-page":"683","article-title":"Expression of hTERT mRNA in a mortal liver cell line during S phase without detectable telomerase activity","volume":"15","author":"Nagao K","year":"2005","unstructured":"K Nagao, et al., Expression of hTERT mRNA in a mortal liver cell line during S phase without detectable telomerase activity. 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