{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T11:18:07Z","timestamp":1786792687555,"version":"build-2736575974"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2008,6,1]],"date-time":"2008-06-01T00:00:00Z","timestamp":1212278400000},"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":["Clin Vaccine Immunol"],"published-print":{"date-parts":[[2008,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Comparative genomics has identified several regions of difference (RDs) of\n            <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n            that are deleted or absent in\n            <jats:italic>Mycobacterium bovis<\/jats:italic>\n            BCG vaccines. To determine their relevance for diagnostic and vaccine applications, it is imperative that efficient methods are developed to test the encoded proteins for immunological reactivity. In this study, we have used 220 synthetic peptides covering sequences of 12 open reading frames (ORFs) of RD1 and tested them as a single pool (RD1\n            <jats:sub>pool<\/jats:sub>\n            ) with peripheral blood mononuclear cells obtained from pulmonary tuberculosis (TB) patients and\n            <jats:italic>M. bovis<\/jats:italic>\n            BCG-vaccinated healthy subjects in Th1 cell assays that measure antigen-induced proliferation and IFN-\u03b3 secretion. The results showed that RD1\n            <jats:sub>pool<\/jats:sub>\n            induced strong responses in both TB patients and BCG-vaccinated healthy subjects. The subsequent testing of peptide pools of individual ORFs revealed that all ORFs induced positive responses in a portion of donors, but PPE68, CFP10, and ESAT6 induced strong responses in TB patients and PPE68 induced strong responses in BCG-vaccinated healthy subjects. In addition, HLA-DR and -DQ typing of donors and HLA-DR binding prediction analysis of proteins suggested HLA-promiscuous presentation of PPE68, CFP10, and ESAT6. Further testing of individual peptides showed that a single peptide of PPE68 (121-VLTATNFFGINTIPIALTEMDYFIR-145) was immunodominant. The search for sequence homology revealed that a part of this peptide, 124-ATNFFGINTIPIAL-137, was present in several PPE family proteins of\n            <jats:italic>M. tuberculosis<\/jats:italic>\n            and\n            <jats:italic>M. bovis<\/jats:italic>\n            BCG vaccines. Further experiments limited the promiscuous and immunodominant epitope region to the 10-amino-acid cross-reactive sequence 127-FFGINTIPIA-136.\n          <\/jats:p>","DOI":"10.1128\/cvi.00056-08","type":"journal-article","created":{"date-parts":[[2008,4,10]],"date-time":"2008-04-10T01:41:50Z","timestamp":1207791710000},"page":"916-924","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":52,"title":["Efficient Testing of Large Pools of\n            <i>Mycobacterium tuberculosis<\/i>\n            RD1 Peptides and Identification of Major Antigens and Immunodominant Peptides Recognized by Human Th1 Cells"],"prefix":"10.1128","volume":"15","author":[{"given":"Abu S.","family":"Mustafa","sequence":"first","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raja'a","family":"Al-Attiyah","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumaila N. M.","family":"Hanif","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatema A.","family":"Shaban","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1046\/j.1365-3083.1999.00531.x","volume":"49","year":"1999","unstructured":"Ahmad, S., H. A. Amoudy, J. E. Thole, D. B. Young, and A. S. Mustafa. 1999. Identification of a novel protein antigen encoded by a Mycobacterium tuberculosis-specific RD1 region gene. Scand. J. Immunol.49:515-522.","journal-title":"Scand. J. Immunol."},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1111\/j.1365-2249.2006.03133.x","volume":"145","year":"2006","unstructured":"Al-Attiyah, R., A. El-Shazly, and A. S. Mustafa. 2006. Assessment of in vitro immunity to Mycobacterium tuberculosis in a human peripheral blood infection model using a luciferase reporter construct of M. tuberculosis H37Rv. Clin. Exp. Immunol.145:520-527.","journal-title":"Clin. Exp. Immunol."},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/j.0300-9475.2004.01349.x","volume":"59","year":"2004","unstructured":"Al-Attiyah, R., and A. S. Mustafa. 2004. Computer-assisted prediction of HLA-DR binding and experimental analysis for human promiscuous Th1-cell peptides in the 24 kDa secreted lipoprotein (LppX) of Mycobacterium tuberculosis. Scand. J. Immunol.59:16-24.","journal-title":"Scand. J. Immunol."},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/j.1365-2249.2004.02609.x","volume":"138","year":"2004","unstructured":"Al-Attiyah, R., and A. S. Mustafa, A. T. Abal, A. S. El-Shamy, W. Dalemans, and Y. A. Skeiky. 2004. In vitro cellular immune responses to complex and newly defined recombinant antigens of Mycobacterium tuberculosis. Clin. Exp. Immunol.138:139-144.","journal-title":"Clin. Exp. Immunol."},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0928-8244(03)00166-4","volume":"38","year":"2003","unstructured":"Al-Attiyah, R., A. S. Mustafa, A. T. Abal, N. M. Madi, and P. Andersen. 2003. Restoration of mycobacterial antigen-induced proliferation and interferon-gamma responses in peripheral blood mononuclear cells of tuberculosis patients upon effective chemotherapy. FEMS Immunol. Med. Microbiol.38:249-256.","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.4.1953-1960.2003"},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1159\/000090919","volume":"15","year":"2006","unstructured":"Amoudy, H. A., M. B. Al-Turab, and A. S. Mustafa. 2006. Identification of transcriptionally active open reading frames within the RD1 genomic segment of Mycobacterium tuberculosis. Med. Princ. Pract.15:137-144.","journal-title":"Med. Princ. Pract."},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1111\/j.1365-3083.2007.01961.x","volume":"66","year":"2007","unstructured":"Amoudy, H. A., S. Ahmad, J. E. Thole, and A. S. Mustafa. 2007. Demonstration of in vivo expression of a hypothetical open reading frame (ORF-14) encoded by the RD1 region of Mycobacterium tuberculosis. Scand. J. Immunol.66:422-425.","journal-title":"Scand. J. Immunol."},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/S0140-6736(00)02742-2","volume":"356","year":"2000","unstructured":"Andersen, P., M. E. Munk, J. M. Pollock, and T. M. Doherty. 2000. Specific immune-based diagnosis of tuberculosis. Lancet356:1099-1104.","journal-title":"Lancet"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.6.3314-3321.2000"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/S1286-4579(03)00205-3","volume":"5","year":"2003","unstructured":"Daugelat, S., J. Kowall, J. Mattow, D. Bumann, R. Winter, R. Hurwits, and S. H. Kaufmann. 2003. The RD1 proteins of Mycobacterium tuberculosis: expression in Mycobacterium smegmatis and biochemical characterization. Microbes Infect.5:1082-1095.","journal-title":"Microbes Infect."},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.4.2170-2176.2004"},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"6938","DOI":"10.4049\/jimmunol.172.11.6938","volume":"172","year":"2004","unstructured":"Demissie, A., M. Abebe, A. Aseffa, G. Rook, H. Fletcher, A. Zumla, K. Weldingh, I. Brock, P. Andersen, T. M. Doherty, and the VACSEL Study Group. 2004. Healthy individuals that control a latent infection with Mycobacterium tuberculosis express high levels of Th1 cytokines and the IL-4 antagonist IL-4delta2. J. Immunol.172:6938-6943.","journal-title":"J. Immunol."},{"key":"e_1_3_2_15_2","doi-asserted-by":"crossref","first-page":"S135","DOI":"10.1016\/S1526-0542(04)90025-5","volume":"5","year":"2004","unstructured":"Enarson, D. A. 2004. Use of the tuberculin skin test in children. Paediatr. Respir. Rev.5(Suppl. A):S135-S137.","journal-title":"Paediatr. Respir. Rev."},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.tube.2003.08.010","volume":"84","year":"2004","unstructured":"Flynn, J. L. 2004. Immunology of tuberculosis and implications in vaccine development. Tuberculosis (Edinburgh)84:93-101.","journal-title":"Tuberculosis (Edinburgh)"},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1046\/j.1365-2958.1999.01383.x","volume":"32","year":"1999","unstructured":"Gordon, S. V., R. Brosch, A. Billault, T. Garnier, K. Eiglmeier, and S. T. Cole. 1999. Identification of variable regions in the genomes of tubercle bacilli using bacterial artificial chromosome arrays. Mol. Microbiol.32:643-655.","journal-title":"Mol. Microbiol."},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/0022-1759(86)90503-X","volume":"92","year":"1986","unstructured":"Hao, X. S., J. M. Le, J. Vilcek, and T. W. Chang. 1986. Determination of human T cell activity in response to allogeneic cells and mitogens. An immunochemical assay for gamma-interferon is more sensitive and specific than a proliferation assay. Immunol. Methods92:59-63.","journal-title":"Immunol. Methods"},{"key":"e_1_3_2_19_2","first-page":"415","volume":"100","year":"2006","unstructured":"Harries, A. D., and C. Dye. 2006. Tuberculosis. Ann. Trop. Med. Parasitol.100:415-431.","journal-title":"Ann. Trop. Med. Parasitol."},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.vaccine.2006.07.020","volume":"25","year":"2007","unstructured":"Hesseling, A. C., B. J. Marais, R. P. Gie, H. S. Schaaf, P. E. Fine, P. Godfrey-Faussett, and N. Beyers. 2007. The risk of disseminated Bacille Calmette-Guerin (BCG) disease in HIV-infected children. Vaccine25:14-18.","journal-title":"Vaccine"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.43.5.2070-2074.2005"},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1086\/318081","volume":"183","year":"2001","unstructured":"Lalvani, A., P. Nagvenkar, Z. Udwadia, A. A. Pathan, K. A. Wilkinson, J. S. Shastri, K. Ewer, A. V. Hill, A. Mehta, and C. Rodrigues. 2001. Enumeration of T cells specific for RD1-encoded antigens suggests a high prevalence of latent Mycobacterium tuberculosis infection in healthy urban Indians. J. Infect. Dis.183:469-477.","journal-title":"J. Infect. Dis."},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.5.2574-2581.2004"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.5.1274-1282.1996"},{"key":"e_1_3_2_25_2","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/S0198-8859(99)00137-8","volume":"61","year":"2000","unstructured":"Mustafa, A. S. 2000. HLA-restricted immune response to mycobacterial antigens: relevance to vaccine design. Hum. Immunol.61:166-171.","journal-title":"Hum. Immunol."},{"key":"e_1_3_2_26_2","doi-asserted-by":"crossref","first-page":"157","DOI":"10.2174\/1389201013378707","volume":"2","year":"2001","unstructured":"Mustafa, A. S. 2001. Biotechnology in the development of new vaccines and diagnostic reagents against tuberculosis. Curr. Pharm. Biotechnol.2:157-173.","journal-title":"Curr. Pharm. Biotechnol."},{"key":"e_1_3_2_27_2","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0161-5890(02)00048-2","volume":"39","year":"2002","unstructured":"Mustafa, A. S. 2002. Development of new vaccines and diagnostic reagents against tuberculosis. Mol. Immunol.39:113-119.","journal-title":"Mol. Immunol."},{"key":"e_1_3_2_28_2","first-page":"47","year":"2005","unstructured":"Mustafa, A. S. 2005. Progress towards the development of new anti-tuberculosis vaccines, p. 47-76. In L. T. Smithe (ed.), Focus on tuberculosis research. Nova Science Publishers, Inc., New York, NY.","journal-title":"Focus on tuberculosis research."},{"key":"e_1_3_2_29_2","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.tube.2005.08.006","volume":"85","year":"2005","unstructured":"Mustafa, A. S. 2005. Recombinant and synthetic peptides to identify Mycobacterium tuberculosis antigens and epitopes of diagnostic and vaccine relevance. Tuberculosis (Edinburgh)85:367-376.","journal-title":"Tuberculosis (Edinburgh)"},{"key":"e_1_3_2_30_2","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1159\/000086182","volume":"14","year":"2005","unstructured":"Mustafa, A. S. 2005. Mycobacterial gene cloning and expression, comparative genomics, bioinformatics and proteomics in relation to the development of new vaccines and diagnostic reagents. Med. Princ. Pract.14(Suppl. 1):27-34.","journal-title":"Med. Princ. Pract."},{"key":"e_1_3_2_31_2","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1159\/000084629","volume":"14","year":"2005","unstructured":"Mustafa, A. S., A. T. Abal, F. Shaban, A. M. El-Shamy, and H. A. Amoudy. 2005. HLA-DR binding prediction and experimental evaluation of T-cell epitopes of mycolyl transferase 85B (Ag85B), a major secreted antigen of Mycobacterium tuberculosis. Med. Princ. Pract.14:140-146.","journal-title":"Med. Princ. Pract."},{"key":"e_1_3_2_32_2","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1046\/j.1365-3083.1998.00419.x","volume":"48","year":"1998","unstructured":"Mustafa, A. S., H. A. Amoudy, H. G. Wiker, A. T. Abal, P. Ravn, F. Oftung, and P. Andersen. 1998. Comparison of antigen-specific T-cell responses of tuberculosis patients using complex or single antigens of Mycobacterium tuberculosis. Scand. J. Immunol.48:535-543.","journal-title":"Scand. J. Immunol."},{"key":"e_1_3_2_33_2","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1046\/j.1365-2249.2002.01937.x","volume":"130","year":"2002","unstructured":"Mustafa, A. S., P. J. Cockle, F. Shaban, R. G. Hewinson, and H. M. Vordermeier. 2002. Immunogenicity of Mycobacterium tuberculosis RD1 region gene products in infected cattle. Clin. Exp. Immunol.130:37-42.","journal-title":"Clin. Exp. Immunol."},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.12.5595-5602.1994"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.53.3.491-497.1986"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.61.12.5294-5301.1993"},{"key":"e_1_3_2_37_2","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/j.1574-695X.1998.tb01208.x","volume":"22","year":"1998","unstructured":"Mustafa, A. S., K. E. Lundin, and F. Oftung. 1998. Isolation of recombinant phage clones expressing mycobacterial T cell antigens by screening a recombinant DNA library with human CD4+ Th1 clones. FEMS Immunol. Med. Microbiol.22:205-216.","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.11.5683-5689.1999"},{"key":"e_1_3_2_39_2","doi-asserted-by":"crossref","first-page":"S201","DOI":"10.1086\/313862","volume":"30","year":"2000","unstructured":"Mustafa, A. S., F. Oftung, H. A. Amoudy, N. M. Madi, A. T. Abal, F. Shaban, I. Rosen Krands, and P. Andersen. 2000. Multiple epitopes from the Mycobacterium tuberculosis ESAT-6 antigen are recognized by antigen-specific human T cell lines. Clin. Infect. Dis.30(Suppl. 3):S201-205.","journal-title":"Clin. Infect. Dis."},{"key":"e_1_3_2_40_2","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.tube.2005.05.001","volume":"86","year":"2006","unstructured":"Mustafa, A. S., and F. A. Shaban. 2006. ProPred analysis and experimental evaluation of promiscuous T-cell epitopes of three major secreted antigens of Mycobacterium tuberculosis. Tuberculosis (Edinburgh)86:115-124.","journal-title":"Tuberculosis (Edinburgh)"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.7.3933-3940.2000"},{"key":"e_1_3_2_42_2","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1046\/j.1365-3083.2003.01204.x","volume":"57","year":"2003","unstructured":"Mustafa, A. S., F. A. Shaban, R. Al-Attiyah, A. T. Abal, A. M. El-Shamy, P. Andersen, and F. Oftung. 2003. Human Th1 cell lines recognize the Mycobacterium tuberculosis ESAT-6 antigen and its peptides in association with frequently expressed HLA class II molecules. Scand. J. Immunol.57:125-134.","journal-title":"Scand. J. Immunol."},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01660-05"},{"key":"e_1_3_2_44_2","first-page":"134","volume":"49","year":"2003","unstructured":"Mustafa Abu, S., and R. Al-Attiyah. 2003. Tuberculosis: looking beyond BCG vaccines. J. Postgrad. Med.49:134-140.","journal-title":"J. Postgrad. Med."},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.12.5411-5418.1994"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.11.6116-6123.2003"},{"key":"e_1_3_2_47_2","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1517\/14656566.8.8.1035","volume":"8","year":"2007","unstructured":"Padayatchi, N., and G. Friedland. 2007. Managing multiple and extensively drug-resistant tuberculosis and HIV. Expert Opin. Pharmacother.8:1035-1037.","journal-title":"Expert Opin. Pharmacother."},{"key":"e_1_3_2_48_2","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1086\/314640","volume":"179","year":"1999","unstructured":"Ravn, P., A. Demissie, T. Eguale, H. Wondwosson, D. Lein, H. A. Amoudy, A. S. Mustafa, A. K. Jensen, A. Holm, I. Rosenkrands, F. Oftung, J. Olobo, F. von Reyn, and P. Andersen. 1999. Human T cell responses to the ESAT-6 antigen from Mycobacterium tuberculosis. J. Infect. Dis.179:637-645.","journal-title":"J. Infect. Dis."},{"key":"e_1_3_2_49_2","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1093\/bioinformatics\/17.12.1236","volume":"17","year":"2001","unstructured":"Singh, H., and G. P. S. Raghava. 2001. ProPred: Prediction of HLA-DR binding sites. Bioinformatics17:1236-1237.","journal-title":"Bioinformatics"},{"key":"e_1_3_2_50_2","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/S0140-6736(06)68507-3","volume":"367","year":"2006","unstructured":"Trunz, B. B., P. Fine, and C. Dye. 2006. Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness. Lancet367:1173-1180.","journal-title":"Lancet"},{"key":"e_1_3_2_51_2","first-page":"443","volume":"22","year":"2006","unstructured":"Zhang, H., C. H. Shi, Y. Xue, Y. L. Bai, L. M. Wang, and Z. K. Xu. 2006. Immune response and protective efficacy induced by fusion protein ESAT6-CFP10 of M. tuberculosis in mice. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi22:443-446.","journal-title":"Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi"}],"container-title":["Clinical and Vaccine Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CVI.00056-08","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CVI.00056-08","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T20:40:23Z","timestamp":1627591223000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/CVI.00056-08"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,6]]},"references-count":50,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2008,6]]}},"alternative-id":["10.1128\/CVI.00056-08"],"URL":"https:\/\/doi.org\/10.1128\/cvi.00056-08","relation":{},"ISSN":["1556-6811","1556-679X"],"issn-type":[{"value":"1556-6811","type":"print"},{"value":"1556-679X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,6]]},"assertion":[{"value":"2008-01-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-03-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}