{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T10:52:46Z","timestamp":1791024766823,"version":"4.1.0"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2000,5,1]],"date-time":"2000-05-01T00:00:00Z","timestamp":957139200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2000,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The demonstrated utility of the nucleoside analog ribavirin in the treatment of certain viral diseases can be ascribed to its multiple distinct properties. These properties may vary in relative importance in differing viral disease conditions and include the direct inhibition of viral replication, the promotion of T-cell-mediated immune responses via an enhanced type 1 cytokine response, and a reduction of circulating alanine aminotransferase (ALT) levels associated with hepatic injury. Ribavirin also has certain known toxicities, including the induction of anemia upon chronic administration. To determine if all these properties are linked, we compared the<jats:sc>d<\/jats:sc>-nucleoside ribavirin to its<jats:sc>l<\/jats:sc>-enantiomer (ICN 17261) with regard to these properties. Strong similarities were seen for these two compounds with respect to induction of type 1 cytokine bias in vitro, enhancement of type 1 cytokine responses in vivo, and the reduction of serum ALT levels in a murine hepatitis model. In contrast, ICN 17261 had no in vitro antiviral activity against a panel of RNA and DNA viruses, while ribavirin exhibited its characteristic activity profile. Importantly, the preliminary in vivo toxicology profile of ICN 17261 is significantly more favorable than that of ribavirin. Administration of 180 mg of ICN 17261 per kg of body weight to rats by oral gavage for 4 weeks generated substantial serum levels of drug but no observable clinical pathology, whereas equivalent doses of ribavirin induced a significant anemia and leukopenia. Thus, structural modification of ribavirin can dissociate its immunomodulatory properties from its antiviral and toxicologic properties, resulting in a compound (ICN 17261) with interesting therapeutic potential.<\/jats:p>","DOI":"10.1128\/aac.44.5.1276-1283.2000","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:06:42Z","timestamp":1027764402000},"page":"1276-1283","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":52,"title":["The Ribavirin Analog ICN 17261 Demonstrates Reduced Toxicity and Antiviral Effects with Retention of both Immunomodulatory Activity and Reduction of Hepatitis-Induced Serum Alanine Aminotransferase Levels"],"prefix":"10.1128","volume":"44","author":[{"given":"Robert C.","family":"Tam","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Immunology1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanda","family":"Ramasamy","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Chemistry2 Laboratories, ICN Research Department, ICN Pharmaceuticals, Inc., Costa Mesa, California 92626"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josie","family":"Bard","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Immunology1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharati","family":"Pai","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Immunology1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charmaine","family":"Lim","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Immunology1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devron R.","family":"Averett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1002\/(SICI)1521-4141(199805)28:05<1534::AID-IMMU1534>3.0.CO;2-R","article-title":"Sequential production of IL-2, IFN-gamma, and IL-10 by individual staphylococcal enterotoxin B-activated T helper lymphocytes.","volume":"28","author":"Assenmacher M.","year":"1998","unstructured":"Assenmacher M. Lohning M. Sheffold A. Manz R. A. Schmitz J. Radbruch A. Sequential production of IL-2, IFN-gamma, and IL-10 by individual staphylococcal enterotoxin B-activated T helper lymphocytes. Eur. J. Immunol. 28 1998 1534 1543","journal-title":"Eur. J. Immunol."},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1002\/ijc.2910370318","article-title":"Comparative inhibitory effects of suramin and other selected compounds on the infectivity and replication of human T-cell lymphotropic virus (HTLV-III)\/lymphadenopathy-associated virus (LAV).","volume":"37","author":"Balzarini J.","year":"1986","unstructured":"Balzarini J. Mitsuya H. De Clerq E. Broder S. Comparative inhibitory effects of suramin and other selected compounds on the infectivity and replication of human T-cell lymphotropic virus (HTLV-III)\/lymphadenopathy-associated virus (LAV). Int. J. Cancer. 37 1986 451 457","journal-title":"Int. J. Cancer."},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1177\/095632029700800306","article-title":"Acyclic phosphonomethylether nucleoside inhibitors of respiratory viruses.","volume":"8","author":"Barnard D. L.","year":"1997","unstructured":"Barnard D. L. Bischofberger N. Kim C. U. Huffman J. H. Sidwell R. W. Dougherty J. P. Lew W. Williams M. A. Yang W. Acyclic phosphonomethylether nucleoside inhibitors of respiratory viruses. Antivir. Chem. Chemother. 8 1997 223 233","journal-title":"Antivir. Chem. Chemother."},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0166-3542(96)01019-4","article-title":"Potent inhibition of respiratory syncytial virus by polyoxometalates of several structural classes.","volume":"34","author":"Barnard D. L.","year":"1997","unstructured":"Barnard D. L. Hill C. L. Gage T. Matheson J. E. Huffman J. H. Sidwell R. W. Otto M. J. Schinazi R. F. Potent inhibition of respiratory syncytial virus by polyoxometalates of several structural classes. Antiviral Res. 34 1997 27 37","journal-title":"Antiviral Res."},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1021\/jm00058a001","article-title":"Modulation of leukocyte genetic expression by novel purine nucleoside analogues. A new approach to antitumor and antiviral agents.","volume":"36","author":"Bonnet P. A.","year":"1993","unstructured":"Bonnet P. A. Robins R. K. Modulation of leukocyte genetic expression by novel purine nucleoside analogues. A new approach to antitumor and antiviral agents. J. Med. Chem. 36 1993 635 653","journal-title":"J. Med. Chem."},{"key":"e_1_3_2_7_2","first-page":"215A","article-title":"Differential effect of IFN-alpha 2b and ribavirin on the HCV-RNA level in primary cultures of human hepatocytes derived from chronic HCV carriers and of human hepatocytes infected in vitro.","volume":"26","author":"Clarysse C.","year":"1997","unstructured":"Clarysse C. Nevens F. Pirenne J. Carucci P. Aerts R. Soumillion A. Roberts N. Yap S. H. Differential effect of IFN-alpha 2b and ribavirin on the HCV-RNA level in primary cultures of human hepatocytes derived from chronic HCV carriers and of human hepatocytes infected in vitro. Hepatology 26 1997 215A","journal-title":"Hepatology"},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1136\/gut.44.3.424","article-title":"Hepatitis C virus (HCV) specific immune responses in anti-HCV positive patients without hepatitis C viraemia.","volume":"44","author":"Cramp M. E.","year":"1999","unstructured":"Cramp M. E. Carucci P. Rossol S. Chokshi S. Maertens G. Williams R. Naoumov N. V. Hepatitis C virus (HCV) specific immune responses in anti-HCV positive patients without hepatitis C viraemia. Gut 44 1999 424 429","journal-title":"Gut"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/S0016-5085(00)70217-4","article-title":"Hepatitis C virus-specific T cell reactivity during interferon and ribavirin treatment in chronic hepatitis C.","volume":"118","author":"Cramp M. E.","year":"2000","unstructured":"Cramp M. E. Rossol S. Chokshi S. Carucci P. Williams R. Naoumov N. V. Hepatitis C virus-specific T cell reactivity during interferon and ribavirin treatment in chronic hepatitis C. Gastroenterology 118 2000 346 355","journal-title":"Gastroenterology"},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1056\/NEJM199811193392102","article-title":"Interferon alpha-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C virus. International Hepatitis Interventional Therapy Group.","volume":"339","author":"Davis G. L.","year":"1998","unstructured":"Davis G. L. Esteban-Mur R. Rustgi V. Hoefs J. Gordon S. C. Trepo C. Schiffman M. L. Zeuzem S. Craxi A. Ling M. H. Albrecht J. Interferon alpha-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C virus. International Hepatitis Interventional Therapy Group. N. Engl. J. Med. 339 1998 1493 1499","journal-title":"N. Engl. J. Med."},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-123-12-199512150-00001"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/S0168-8278(96)80225-X","article-title":"Ribavirin treatment for patients with chronic hepatitis C: results of a placebo-controlled study.","volume":"25","author":"Dusheiko G.","year":"1996","unstructured":"Dusheiko G. Main J. Thomas H. Reichard O. Lee C. Dhillon A. Rassam S. Fryden A. Reesink H. Bassendine M. Norkrans G. Cuypers T. Lelie N. Telfer P. Watson J. Weegink C. Sillikens P. Weiland O. Ribavirin treatment for patients with chronic hepatitis C: results of a placebo-controlled study. J. Hepatol. 25 1996 591 598","journal-title":"J. Hepatol."},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0168-8278(05)80387-3","article-title":"Therapy of chronic hepatitis B with a 6-month course of ribavirin.","volume":"21","author":"Fried M. W.","year":"1994","unstructured":"Fried M. W. Fong T. L. Swain M. G. Park Y. Beames M. P. Banks S. M. Hoofnagle J. H. Di Bisceglie A. M. Therapy of chronic hepatitis B with a 6-month course of ribavirin. J. Hepatol. 21 1994 145 150","journal-title":"J. Hepatol."},{"key":"e_1_3_2_14_2","first-page":"190A","article-title":"Interferon-a2b\/ribavirin (Rebetron\u2122) treatment for chronic hepatitis C\u2014population pharmacokinetics and pharmacodynamics of ribavirin.","volume":"30","author":"Glue P.","year":"1999","unstructured":"Glue P. Jen F. Gupta S. K. Lau J. Y. N. Interferon-a2b\/ribavirin (Rebetron\u2122) treatment for chronic hepatitis C\u2014population pharmacokinetics and pharmacodynamics of ribavirin. Hepatology 30 1999 190A","journal-title":"Hepatology"},{"key":"e_1_3_2_15_2","first-page":"1552","article-title":"Selective modulation of elements of the immune system by low molecular weight nucleosides.","volume":"274","author":"Goodman M. G.","year":"1995","unstructured":"Goodman M. G. Reitz A. B. Chen R. Bobardt M. D. Goodman J. H. Pope B. L. Selective modulation of elements of the immune system by low molecular weight nucleosides. J. Pharmacol. Exp. Ther. 274 1995 1552 1557","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1056\/NEJM198306163082403","article-title":"Aerosolized ribavirin treatment of infants with respiratory syncytial viral infection.","volume":"308","author":"Hall C. B.","year":"1983","unstructured":"Hall C. B. McBride J. T. Walsh E. E. Bell D. M. Gala C. L. Hildreth S. Ten Eyck L. G. Hall W. J. Aerosolized ribavirin treatment of infants with respiratory syncytial viral infection. N. Engl. J. Med. 308 1983 1443 1447","journal-title":"N. Engl. J. Med."},{"key":"e_1_3_2_17_2","first-page":"354A","article-title":"Direct antiviral activity of ribavirin: hepatitis C virus NS5B polymerase incorporates ribavirin triphosphate into nascent RNA products.","volume":"30","author":"Hong Z.","year":"1999","unstructured":"Hong Z. Ferrari E. Wright-Minotogue J. Skelton A. Glue P. Zhong W. Lau J. Y. N. Direct antiviral activity of ribavirin: hepatitis C virus NS5B polymerase incorporates ribavirin triphosphate into nascent RNA products. Hepatology 30 1999 354A","journal-title":"Hepatology"},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1177\/095632029700800201","article-title":"Influenza virus-inhibitory effects of a series of germanium- and silicon-centered polyoxometalates.","volume":"8","author":"Huffman J. H.","year":"1997","unstructured":"Huffman J. H. Sidwell R. W. Barnard D. L. Morrison A. Otto M. J. Hill C. L. Schinazi R. F. Influenza virus-inhibitory effects of a series of germanium- and silicon-centered polyoxometalates. Antivir. Chem. Chemother. 8 1997 75 83","journal-title":"Antivir. Chem. Chemother."},{"key":"e_1_3_2_19_2","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1099\/0022-1317-79-10-2381","article-title":"The antiviral compound ribavirin modulates the T helper (Th)1\/Th2 subset balance in hepatitis B and C virus-specific immune responses.","volume":"79","author":"Hultgren C.","year":"1998","unstructured":"Hultgren C. Milich D. R. Weiland O. S\u00e4llberg M. The antiviral compound ribavirin modulates the T helper (Th)1\/Th2 subset balance in hepatitis B and C virus-specific immune responses. J. Gen. Virol. 79 1998 2381 2391","journal-title":"J. Gen. Virol."},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.37.3.441"},{"key":"e_1_3_2_21_2","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/j.1365-2893.1997.tb00178.x","article-title":"The role of immune responses in the pathogenesis of hepatitis C.","volume":"4","author":"Koziel M. J.","year":"1997","unstructured":"Koziel M. J. The role of immune responses in the pathogenesis of hepatitis C. J. Vir. Hepatitis 4 (Suppl.2) 1997 31 41","journal-title":"J. Vir. Hepatitis"},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1002\/hep.510280332","article-title":"Cellular immunity to hepatitis C virus core protein and the response to interferon in patients with chronic hepatitis C.","volume":"28","author":"Lasarte J. J.","year":"1998","unstructured":"Lasarte J. J. Garcia-Granero M. Lopez A. Casares N. Garcia N. Civeira M. P. Borras-Cuesta F. Prieto J. Cellular immunity to hepatitis C virus core protein and the response to interferon in patients with chronic hepatitis C. Hepatology 28 1998 815 822","journal-title":"Hepatology"},{"key":"e_1_3_2_23_2","first-page":"790","article-title":"The role of hepatitis C virus specific CD4+ T lymphocytes in acute and chronic hepatitis C.","volume":"24","author":"Lechmann M.","year":"1996","unstructured":"Lechmann M. Ihlenfeldt H. G. Braunschweiger I. Giers G. Jung G. Matz B. Kaiser R. Sauerbruch T. Spengler U. The role of hepatitis C virus specific CD4+ T lymphocytes in acute and chronic hepatitis C. Hepatology 24 1996 790 795","journal-title":"Hepatology"},{"key":"e_1_3_2_24_2","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0168-8278(98)80175-X","article-title":"Effect of ribavirin on virus load and quasispecies distribution in patients infected with hepatitis C virus.","volume":"29","author":"Lee J. H.","year":"1998","unstructured":"Lee J. H. von Wagner M. Roth W. K. Teuber G. Sarrazin C. Zeuzem S. Effect of ribavirin on virus load and quasispecies distribution in patients infected with hepatitis C virus. J. Hepatol. 29 1998 29 35","journal-title":"J. Hepatol."},{"key":"e_1_3_2_25_2","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1002\/hep.1840070418","article-title":"Experimental transmission of duck hepatitis B virus to Pekin ducks and to domestic geese.","volume":"7","author":"Marion P. L.","year":"1987","unstructured":"Marion P. L. Cullen J. M. Azcarraga R. R. Van Davelaar M. J. Robinson W. S. Experimental transmission of duck hepatitis B virus to Pekin ducks and to domestic geese. Hepatology 7 1987 724 731","journal-title":"Hepatology"},{"key":"e_1_3_2_26_2","first-page":"2381","article-title":"Effects of the ribavirin-interferon alpha combination on cultured peripheral blood mononuclear cells from chronic hepatitis C patients.","volume":"79","author":"Martin M. J.","year":"1998","unstructured":"Martin M. J. Navas S. Quiroga J. A. Pardo M. Carreno V. Effects of the ribavirin-interferon alpha combination on cultured peripheral blood mononuclear cells from chronic hepatitis C patients. Cytokine 79 1998 2381 2391","journal-title":"Cytokine"},{"key":"e_1_3_2_27_2","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/S0140-6736(84)92060-9","article-title":"Ribavirin suppresses replication of lymphadenopathy-associated virus in cultures of human adult T lymphocytes.","author":"McCormick J. B.","year":"1984","unstructured":"McCormick J. B. Getchell J. P. Mitchell S. W. Hicks D. R. Ribavirin suppresses replication of lymphadenopathy-associated virus in cultures of human adult T lymphocytes. Lancet ii 1984 1367 1369","journal-title":"Lancet"},{"key":"e_1_3_2_28_2","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1056\/NEJM199811193392101","article-title":"Interferon alpha 2B alone or in combination with ribavirin as initial treatment for chronic hepatitis C.","volume":"339","author":"McHutchinson J. G.","year":"1998","unstructured":"McHutchinson J. G. Gordon S. C. Schiff E. R. Mitchell M. D. Shiffmann M. L. Lee W. M. Rustgi V. K. Goodman Z. D. Ling M. H. Cort S. Albrecht J. K. Interferon alpha 2B alone or in combination with ribavirin as initial treatment for chronic hepatitis C. N. Engl. J. Med. 339 1998 1485 1492","journal-title":"N. Engl. J. Med."},{"key":"e_1_3_2_29_2","doi-asserted-by":"crossref","first-page":"21220","DOI":"10.1016\/S0021-9258(19)36820-6","article-title":"Phosphorylation of carbovir enantiomers by cellular enzymes determines the stereoselectivity of antiviral activity.","volume":"267","author":"Miller W. H.","year":"1992","unstructured":"Miller W. H. Daluge S. M. Garvey E. P. Hopkins S. Reardon J. E. Boyd F. L. Miller R. L. Phosphorylation of carbovir enantiomers by cellular enzymes determines the stereoselectivity of antiviral activity. J. Biol. Chem. 267 1992 21220 21224","journal-title":"J. Biol. Chem."},{"key":"e_1_3_2_30_2","first-page":"1608","article-title":"Critical involvement of interferon-gamma in the pathogenesis of T cell activation-associated hepatitis and regulatory mechanisms of interleukin-6 for the manifestations of hepatitis.","volume":"23","author":"Mizuhara H.","year":"1996","unstructured":"Mizuhara H. Uno M. Seki N. Yamashita M. Yamakoka M. Ogawa T. Kaneda K. Fujii T. Senoh H. Fujiwara H. Critical involvement of interferon-gamma in the pathogenesis of T cell activation-associated hepatitis and regulatory mechanisms of interleukin-6 for the manifestations of hepatitis. Hepatology 23 1996 1608 1615","journal-title":"Hepatology"},{"key":"e_1_3_2_31_2","doi-asserted-by":"crossref","first-page":"3487","DOI":"10.4049\/jimmunol.160.7.3487","article-title":"Ribavirin inhibits viral-induced macrophage production of tumor necrosis factor, interleukin-1, procoagulant activity fgl2 prothrombinase and preserves Th1 cytokine production but inhibits Th2 cytokine response.","volume":"160","author":"Ning Q.","year":"1998","unstructured":"Ning Q. Brown D. Parodo J. Cattral M. Fung L. Gorczynski R. Cole E. Fung L. Ding J. W. Liu M. F. Rotstein O. Phillips M. J. Levy G. Ribavirin inhibits viral-induced macrophage production of tumor necrosis factor, interleukin-1, procoagulant activity fgl2 prothrombinase and preserves Th1 cytokine production but inhibits Th2 cytokine response. J. Immunol. 160 1998 3487 3493","journal-title":"J. Immunol."},{"key":"e_1_3_2_32_2","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1097\/00004836-199906000-00006","article-title":"Changes in serum hepatitis C virus RNA in interferon nonresponders retreated with interferon plus ribavirin: a preliminary report.","volume":"28","author":"Nyberg L.","year":"1999","unstructured":"Nyberg L. Albrecht J. Glue P. Gianelli G. Zambras D. Elliot M. Conrad A. McHutchinson J. Changes in serum hepatitis C virus RNA in interferon nonresponders retreated with interferon plus ribavirin: a preliminary report. J. Clin. Gastroenterol. 28 1999 313 316","journal-title":"J. Clin. Gastroenterol."},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)07124-4"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.40.24449"},{"key":"e_1_3_2_35_2","doi-asserted-by":"crossref","unstructured":"Ramasamy K. R. C. Tam J. Bard and D. R. Averett. Monocyclic L-nucleosides with Type 1 cytokine-inducing activity. J. Med. Chem. 43: 1019\u20131028.","DOI":"10.1021\/jm9905514"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.10.7092-7102.1996"},{"key":"e_1_3_2_37_2","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0140-6736(97)06088-1","article-title":"Randomized, double blind, placebo controlled trial of interferon alpha 2B with and without ribavirin for chronic hepatitis C.","volume":"351","author":"Reichard O.","year":"1998","unstructured":"Reichard O. Norkrans G. Fryden A. Braconier J.-H. Sonnerborg A. Weiland O. Randomized, double blind, placebo controlled trial of interferon alpha 2B with and without ribavirin for chronic hepatitis C. Lancet 351 1998 83 87","journal-title":"Lancet"},{"key":"e_1_3_2_38_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0168-8278(96)80320-5","article-title":"Production of interleukin-2 in response to synthetic peptides from hepatitis C virus E1 protein in patients with chronic hepatitis C: relationship with the response to interferon treatment.","volume":"25","author":"Sarobe P.","year":"1996","unstructured":"Sarobe P. Jauregui J. I. Lasarte J. J. Garcia N. Civeira M. P. Borras-Cuesta F. Prieto J. Production of interleukin-2 in response to synthetic peptides from hepatitis C virus E1 protein in patients with chronic hepatitis C: relationship with the response to interferon treatment. J. Hepatol. 25 1996 1 9","journal-title":"J. Hepatol."},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.177.4050.705"},{"key":"e_1_3_2_40_2","doi-asserted-by":"crossref","first-page":"3709","DOI":"10.4049\/jimmunol.163.7.3709","article-title":"Contact hypersensitivity responses following ribavirin treatment in vivo are influenced by Type 1 cytokine polarization, regulation of IL-10 expression and costimulatory signaling.","volume":"163","author":"Tam R. C.","year":"1999","unstructured":"Tam R. C. Lim C. Bard J. Pai B. Contact hypersensitivity responses following ribavirin treatment in vivo are influenced by Type 1 cytokine polarization, regulation of IL-10 expression and costimulatory signaling. J. Immunol. 163 1999 3709 3717","journal-title":"J. Immunol."},{"key":"e_1_3_2_41_2","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/S0168-8278(99)80093-2","article-title":"Ribavirin polarizes human T cell responses towards a Type 1 cytokine profile.","volume":"30","author":"Tam R. C.","year":"1999","unstructured":"Tam R. C. Pai B. Bard J. Lim C. Averett D. R. Phan U. T. Milovanovic T. Ribavirin polarizes human T cell responses towards a Type 1 cytokine profile. J. Hepatol. 30 1999 376 382","journal-title":"J. Hepatol."},{"key":"e_1_3_2_42_2","doi-asserted-by":"crossref","first-page":"200","DOI":"10.4049\/jimmunol.158.1.200","article-title":"Oligonucleotide-mediated inhibition of CD28 expression induces human T cell hyporesponsiveness and manifests impaired contact hypersensitivity in mice.","volume":"158","author":"Tam R. C.","year":"1997","unstructured":"Tam R. C. Phan U. T. Milovanovic T. Pai B. Lim C. Bard J. He L. Oligonucleotide-mediated inhibition of CD28 expression induces human T cell hyporesponsiveness and manifests impaired contact hypersensitivity in mice. J. Immunol. 158 1997 200 208","journal-title":"J. Immunol."},{"key":"e_1_3_2_43_2","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1002\/hep.510250233","article-title":"Detection of type 2-like T helper cells in hepatitis C virus infection: implications for hepatitis C virus chronicity.","volume":"25","author":"Tsai S. L.","year":"1997","unstructured":"Tsai S. L. Liaw Y. F. Chen M. H. Huang C. Y. Kuo G. C. Detection of type 2-like T helper cells in hepatitis C virus infection: implications for hepatitis C virus chronicity. Hepatology 25 1997 449 458","journal-title":"Hepatology"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/81.8.577"},{"key":"e_1_3_2_45_2","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.4049\/jimmunol.159.2.1012","article-title":"CD30 induction and cytokine profiles in hepatitis C virus core-specific peripheral blood T lymphocytes.","volume":"159","author":"Woitas R. P.","year":"1997","unstructured":"Woitas R. P. Lechmann M. Jung G. Kaiser R. Sauerbach T. Spengler U. CD30 induction and cytokine profiles in hepatitis C virus core-specific peripheral blood T lymphocytes. J. Immunol. 159 1997 1012 1018","journal-title":"J. Immunol."},{"key":"e_1_3_2_46_2","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1084\/jem.183.3.1001","article-title":"T cell populations primed to hapten sensitization in contact hypersensitivity are distinguished by polarized patterns of cytokine production: interferon-gamma (Tc1) effector CD8+ T cells and interleukin 4\/interleukin 10-producing (Th2) negative regulatory CD4+ T cells.","volume":"183","author":"Xu H.","year":"1996","unstructured":"Xu H. Dilulio N. A. Fairchild R. L. T cell populations primed to hapten sensitization in contact hypersensitivity are distinguished by polarized patterns of cytokine production: interferon-gamma (Tc1) effector CD8+ T cells and interleukin 4\/interleukin 10-producing (Th2) negative regulatory CD4+ T cells. J. Exp. Med. 183 1996 1001 1012","journal-title":"J. Exp. Med."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.44.5.1276-1283.2000","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.44.5.1276-1283.2000","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,23]],"date-time":"2023-04-23T15:50:19Z","timestamp":1682265019000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.44.5.1276-1283.2000"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,5]]},"references-count":45,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2000,5]]}},"alternative-id":["10.1128\/AAC.44.5.1276-1283.2000"],"URL":"https:\/\/doi.org\/10.1128\/aac.44.5.1276-1283.2000","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,5]]},"assertion":[{"value":"1999-11-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-02-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-05-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}