{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T20:51:49Z","timestamp":1771015909107,"version":"3.50.1"},"reference-count":48,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"4656","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1984,6,29]]},"abstract":"<jats:p>Molecular hybridization, monoclonal antibody, and electron microscopic analyses showed lymphocytic choriomeningitis virus (strains Armstrong and WE) persistently infecting cells of the islets of Langerhans in BALB\/WEHI mice. When monoclonal or monospecific antibody conjugated with two different fluorochrome dyes was used to mark insulin-containing \u03b2 cells or viral antigens, viral nucleoprotein was identified predominately in \u03b2 cells. Electron microscopy confirmed these findings by showing virions budding from the \u03b2 cells. Persistent infection was associated with chemical evidence of diabetes (hyperglycemia, abnormal glucose tolerance, and normal or low-normal concentrations of insulin). Concentrations of cortisol and insulin-like growth factor in blood were normal, as was the level of growth hormone in the pituitary gland. The virus-infected islet cells showed normal anatomy and cytomorphology. Neither cell lysis nor inflammatory infiltrates were routinely seen. Thus a virus may persistently infect islet cells and provide a biochemical and morphological picture comparable to that of early adult-onset diabetes mellitus in humans.<\/jats:p>","DOI":"10.1126\/science.6203172","type":"journal-article","created":{"date-parts":[[2006,10,5]],"date-time":"2006-10-05T19:41:59Z","timestamp":1160077319000},"page":"1440-1443","source":"Crossref","is-referenced-by-count":73,"title":["Virus Persists in \u03b2 Cells of Islets of Langerhans and Is Associated with Chemical Manifestations of Diabetes"],"prefix":"10.1126","volume":"224","author":[{"given":"Michael B. A.","family":"Oldstone","sequence":"first","affiliation":[{"name":"Department of Immunology, Scripps Clinic and Research Foundation, La Jolla, California 92037"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Southern","sequence":"additional","affiliation":[{"name":"Department of Immunology, Scripps Clinic and Research Foundation, La Jolla, California 92037"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moses","family":"Rodriquez","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, University of California, San Diego, La Jolla, California 92093"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Lampert","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, University of California, San Diego, La Jolla, California 92093"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"221","reference":[{"key":"e_1_2_1_1_1","unstructured":"AHMED R CONCEPTS VIRAL PATHO (1984)."},{"key":"e_1_2_1_2_1","unstructured":"AHMED R NONSEGMENTED NEGATIV (1984)."},{"key":"e_1_2_1_3_1","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/BF01228134","volume":"14","year":"1978","unstructured":"ANDERSSON, A, ISOLATED MOUSE PANCREATIC-ISLETS IN CULTURE - EFFECTS OF SERUM AND DIFFERENT CULTURE MEDIA ON INSULIN PRODUCTION OF ISLETS, DIABETOLOGIA 14: 397 (1978).","journal-title":"DIABETOLOGIA"},{"key":"e_1_2_1_4_1","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S0065-2776(08)60197-2","volume":"30","year":"1980","unstructured":"BUCHMEIER, M.J., ADVANCES IN IMMUNOLOGY 30: 275 (1980).","journal-title":"ADVANCES IN IMMUNOLOGY"},{"key":"e_1_2_1_5_1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0042-6822(78)90047-8","volume":"89","year":"1978","unstructured":"BUCHMEIER, M.J., PROTEIN-STRUCTURE OF LYMPHOCYTIC CHORIOMENINGITIS VIRUS - IDENTIFICATION OF VIRUS STRUCTURAL AND CELL ASSOCIATED POLYPEPTIDES, VIROLOGY 89: 133 (1978).","journal-title":"VIROLOGY"},{"key":"e_1_2_1_6_1","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/0042-6822(79)90042-4","volume":"99","year":"1979","unstructured":"BUCHMEIER, M.J., PROTEIN-STRUCTURE OF LYMPHOCYTIC CHORIOMENINGITIS VIRUS - EVIDENCE FOR A CELL-ASSOCIATED PRECURSOR OF THE VIRION GLYCOPEPTIDES, VIROLOGY 99: 111 (1979).","journal-title":"VIROLOGY"},{"key":"e_1_2_1_7_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/0042-6822(81)90137-9","volume":"113","year":"1981","unstructured":"BUCHMEIER, M.J., MONOCLONAL-ANTIBODIES TO LYMPHOCYTIC CHORIOMENINGITIS AND PICHINDE VIRUSES - GENERATION, CHARACTERIZATION, AND CROSS-REACTIVITY WITH OTHER ARENAVIRUSES, VIROLOGY 113: 73 (1981).","journal-title":"VIROLOGY"},{"key":"e_1_2_1_8_1","first-page":"17","year":"1970","unstructured":"CERASI, E, PATHOGENESIS DIABETE: 17 (1970).","journal-title":"PATHOGENESIS DIABETE"},{"key":"e_1_2_1_9_1","first-page":"161","volume":"19","year":"1975","unstructured":"CRAIGHEAD, J.E., ROLE OF VIRUSES IN PATHOGENESIS OF PANCREATIC DISEASE AND DIABETES-MELLITUS, PROGRESS IN MEDICAL VIROLOGY 19: 161 (1975).","journal-title":"PROGRESS IN MEDICAL VIROLOGY"},{"key":"e_1_2_1_10_1","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1210\/endo-110-2-575","volume":"110","year":"1982","unstructured":"DAUGHADAY, W.H., MEASUREMENT OF SOMATOMEDIN-RELATED PEPTIDES IN FETAL, NEONATAL, AND MATERNAL RAT SERUM BY INSULIN-LIKE GROWTH-FACTOR (IGF)-I RADIOIMMUNOASSAY, IGF-II RADIORECEPTOR ASSAY (RRA), AND MULTIPLICATION-STIMULATING ACTIVITY RRA AFTER ACID-ETHANOL EXTRACTION, ENDOCRINOLOGY 110: 575 (1982).","journal-title":"ENDOCRINOLOGY"},{"key":"e_1_2_1_11_1","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1099\/0022-1317-64-8-1689","volume":"64","year":"1983","unstructured":"DUTKO, F.J., GENOMIC AND BIOLOGICAL VARIATION AMONG COMMONLY USED LYMPHOCYTIC CHORIOMENINGITIS VIRUS-STRAINS, JOURNAL OF GENERAL VIROLOGY 64: 1689 (1983).","journal-title":"JOURNAL OF GENERAL VIROLOGY"},{"key":"e_1_2_1_12_1","first-page":"1007","volume":"2","year":"1979","unstructured":"FAJANS, S.S., ENDOCRINOLOGY 2: 1007 (1979).","journal-title":"ENDOCRINOLOGY"},{"key":"e_1_2_1_13_1","first-page":"307","year":"1980","unstructured":"FELIG, P, METABOLIC CONTROL DI: 307 (1980).","journal-title":"METABOLIC CONTROL DI"},{"key":"e_1_2_1_14_1","first-page":"1069","volume":"2","year":"1979","unstructured":"FIELD, J.B., ENDOCRINOLOGY 2: 1069 (1979).","journal-title":"ENDOCRINOLOGY"},{"key":"e_1_2_1_15_1","first-page":"1775","year":"1982","unstructured":"FOSTER, D, HARRISONS PRINCIPLES: 1775 (1982).","journal-title":"HARRISONS PRINCIPLES"},{"key":"e_1_2_1_16_1","first-page":"3961","volume":"72","year":"1975","unstructured":"GRUNSTEIN, M, COLONY HYBRIDIZATION - METHOD FOR ISOLATION OF CLONED DNAS THAT CONTAIN A SPECIFIC GENE, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 72: 3961 (1975).","journal-title":"PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"},{"key":"e_1_2_1_17_1","first-page":"821","year":"1979","unstructured":"HAM, A, HISTOLOGY: 821 (1979).","journal-title":"HISTOLOGY"},{"key":"e_1_2_1_18_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3181\/00379727-162-40609","volume":"162","year":"1979","unstructured":"KAHN, C.R., ROLE OF INSULIN RECEPTORS AND RECEPTOR ANTIBODIES IN STATES OF ALTERED INSULIN ACTION, PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE 162: 13 (1979).","journal-title":"PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE"},{"key":"e_1_2_1_19_1","first-page":"103","volume":"16","year":"1970","unstructured":"KIPNIS, D.M., ADV INTERNAL MED 16: 103 (1970).","journal-title":"ADV INTERNAL MED"},{"key":"e_1_2_1_20_1","doi-asserted-by":"crossref","first-page":"109","DOI":"10.2337\/diab.31.4.S109","volume":"31","year":"1982","unstructured":"LACY, P. E., DIABETES 31: 109 (1982).","journal-title":"DIABETES"},{"key":"e_1_2_1_21_1","first-page":"167","year":"1976","unstructured":"NERUP, J, ACTA ENDOCRINOLOGICA 205: 167 (1976).","journal-title":"ACTA ENDOCRINOLOGICA"},{"key":"e_1_2_1_22_1","first-page":"62","volume":"241","year":"1979","unstructured":"NOTKINS, A.L., CAUSES OF DIABETES, SCIENTIFIC AMERICAN 241: 62 (1979).","journal-title":"SCIENTIFIC AMERICAN"},{"key":"e_1_2_1_23_1","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1084\/jem.129.3.483","volume":"129","year":"1969","unstructured":"OLDSTONE, MBA, PATHOGENESIS OF CHRONIC DISEASE ASSOCIATED WITH PERSISTENT LYMPHOCYTIC CHORIOMENINGITIS VIRAL INFECTION .I. RELATIONSHIP OF ANTIBODY PRODUCTION TO DISEASE IN NEONATALLY INFECTED MICE, JOURNAL OF EXPERIMENTAL MEDICINE 129: 483 (1969).","journal-title":"JOURNAL OF EXPERIMENTAL MEDICINE"},{"key":"e_1_2_1_24_1","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/300360a0","volume":"300","year":"1982","unstructured":"OLDSTONE, MBA, RESTRICTED EXPRESSION OF VIRAL GLYCOPROTEIN IN CELLS OF PERSISTENTLY INFECTED MICE, NATURE 300: 360 (1982).","journal-title":"NATURE"},{"key":"e_1_2_1_25_1","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1038\/307278a0","volume":"307","year":"1984","unstructured":"OLDSTONE, MBA, VIRAL PERTURBATION OF ENDOCRINE FUNCTION - DISORDERED CELL-FUNCTION LEADS TO DISTURBED HOMEOSTASIS AND DISEASE, NATURE 307: 278 (1984).","journal-title":"NATURE"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7146898"},{"key":"e_1_2_1_27_1","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.2337\/diab.25.12.1154","volume":"25","year":"1976","unstructured":"OLEFSKY, J.M., INSULIN RECEPTOR - ITS ROLE IN INSULIN RESISTANCE OF OBESITY AND DIABETES, DIABETES 25: 1154 (1976).","journal-title":"DIABETES"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.208156"},{"key":"e_1_2_1_29_1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1128\/jvi.20.1.14-21.1976","volume":"20","year":"1976","unstructured":"PETERSON, I, J VIROL 20: 14 (1976).","journal-title":"J VIROL"},{"key":"e_1_2_1_30_1","unstructured":"RAITT M unpublished data."},{"key":"e_1_2_1_31_1","first-page":"151","volume":"14","year":"1980","unstructured":"RAWLS, W.E., COMP VIROL 14: 151 (1980).","journal-title":"COMP VIROL"},{"key":"e_1_2_1_32_1","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1093\/clinids\/5.2.341","volume":"5","year":"1983","unstructured":"RAYFIELD, E.J., VIRUSES MAY BE ETIOLOGIC AGENTS FOR NON-INSULIN-DEPENDENT (TYPE-II) DIABETES, REVIEWS OF INFECTIOUS DISEASES 5: 341 (1983).","journal-title":"REVIEWS OF INFECTIOUS DISEASES"},{"key":"e_1_2_1_33_1","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/0022-2836(77)90052-3","volume":"113","year":"1977","unstructured":"RIGBY, PWJ, LABELING DEOXYRIBONUCLEIC-ACID TO HIGH SPECIFIC ACTIVITY INVITRO BY NICK TRANSLATION WITH DNA-POLYMERASE I, JOURNAL OF MOLECULAR BIOLOGY 113: 237 (1977).","journal-title":"JOURNAL OF MOLECULAR BIOLOGY"},{"key":"e_1_2_1_34_1","first-page":"135","year":"1981","unstructured":"Robbins, S., Basic Pathology: 135 (1981).","journal-title":"Basic Pathology"},{"key":"e_1_2_1_35_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3181\/00379727-162-40608","volume":"162","year":"1979","unstructured":"ROTH, J, RECEPTORS AND RECEPTOR DISORDERS - INTRODUCTION, PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE 162: 3 (1979).","journal-title":"PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE"},{"key":"e_1_2_1_36_1","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1093\/nar\/3.4.863","volume":"3","year":"1976","unstructured":"ROYCHOUDHURY, R, TERMINAL LABELING AND ADDITION OF HOMOPOLYMER TRACTS TO DUPLEX DNA FRAGMENTS BY TERMINAL DEOXYNUCLEOTIDYL TRANSFERASE, NUCLEIC ACIDS RESEARCH 3: 863 (1976).","journal-title":"NUCLEIC ACIDS RESEARCH"},{"key":"e_1_2_1_37_1","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1097\/00007890-197312000-00028","volume":"16","year":"1973","unstructured":"SCHARP, D, TRANSPLANTATION 16: 686 (1973).","journal-title":"TRANSPLANTATION"},{"key":"e_1_2_1_38_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.2337\/diab.29.1.S19","volume":"29","year":"1980","unstructured":"SCHARP, D.W., DIABETES 29 1: 19 (1980).","journal-title":"DIABETES"},{"key":"e_1_2_1_39_1","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1210\/endo-91-3-784","volume":"91","year":"1972","unstructured":"SINHA, Y.N., STUDIES OF GH SECRETION IN MICE BY A HOMOLOGOUS RADIOIMMUNOASSAY FOR MOUSE GH, ENDOCRINOLOGY 91: 784 (1972).","journal-title":"ENDOCRINOLOGY"},{"key":"e_1_2_1_40_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1677\/joe.0.0550031","volume":"55","year":"1972","unstructured":"SINHA, Y.N., EFFECTS OF ADMINISTERING ANTISERA TO MOUSE GROWTH-HORMONE AND PROLACTIN ON GAIN IN LITTER WEIGHT AND ON MAMMARY NUCLEIC-ACID CONTENT OF LACTATING C3H MICE, JOURNAL OF ENDOCRINOLOGY 55: 31 (1972).","journal-title":"JOURNAL OF ENDOCRINOLOGY"},{"key":"e_1_2_1_41_1","unstructured":"Southern P. J. Nonsegmented Negative Strand Viruses (1984)."},{"key":"e_1_2_1_42_1","unstructured":"SOUTHERN P.J. unpublished data."},{"key":"e_1_2_1_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.157.3789.697"},{"key":"e_1_2_1_44_1","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/0005-2787(76)90307-5","volume":"442","year":"1976","unstructured":"TAYLOR, J.M., EFFICIENT TRANSCRIPTION OF RNA INTO DNA BY AVIAN-SARCOMA VIRUS POLYMERASE, BIOCHIMICA ET BIOPHYSICA ACTA 442: 324 (1976).","journal-title":"BIOCHIMICA ET BIOPHYSICA ACTA"},{"key":"e_1_2_1_45_1","first-page":"5201","volume":"77","year":"1980","unstructured":"THOMAS, P.S., HYBRIDIZATION OF DENATURED RNA AND SMALL DNA FRAGMENTS TRANSFERRED TO NITROCELLULOSE, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES 77: 5201 (1980).","journal-title":"PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES"},{"key":"e_1_2_1_46_1","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1084\/jem.145.6.1449","volume":"145","year":"1977","unstructured":"WELSH, R.M., INHIBITION OF IMMUNOLOGICAL INJURY OF CULTURED-CELLS INFECTED WITH LYMPHOCYTIC CHORIOMENINGITIS VIRUS - ROLE OF DEFECTIVE INTERFERING VIRUS IN REGULATING VIRAL ANTIGENIC EXPRESSION, JOURNAL OF EXPERIMENTAL MEDICINE 145: 1449 (1977).","journal-title":"JOURNAL OF EXPERIMENTAL MEDICINE"},{"key":"e_1_2_1_47_1","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/0002-9343(61)90030-4","volume":"31","year":"1961","unstructured":"YALOW, R.S., IMMUNOLOGIC ASPECTS OF INSULIN, AMERICAN JOURNAL OF MEDICINE 31: 882 (1961).","journal-title":"AMERICAN JOURNAL OF MEDICINE"},{"key":"e_1_2_1_48_1","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1056\/NEJM197905243002102","volume":"300","year":"1979","unstructured":"YOON, J.W., VIRUS-INDUCED DIABETES-MELLITUS - ISOLATION OF A VIRUS FROM THE PANCREAS OF A CHILD WITHDIABETIC KETOACIDOSIS, NEW ENGLAND JOURNAL OF MEDICINE 300: 1173 (1979).","journal-title":"NEW ENGLAND JOURNAL OF MEDICINE"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.6203172","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,14]],"date-time":"2024-01-14T15:29:10Z","timestamp":1705246150000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.6203172"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1984,6,29]]},"references-count":48,"journal-issue":{"issue":"4656","published-print":{"date-parts":[[1984,6,29]]}},"alternative-id":["10.1126\/science.6203172"],"URL":"https:\/\/doi.org\/10.1126\/science.6203172","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1984,6,29]]}}}