Comparison of Nucleotide Sequence of P2C Region in Diabetogenic and Non‐Diabetogenic Coxsackie Virus B5 Isolates

The Kaohsiung Journal of Medical Sciences - Tập 20 - Trang 525-532 - 2004
Cheng-Chong Chou1, Kuei-Hsiang Lin1, Guan-Ming Ke1, Yi-Ching Tung1, Jeng-Yin Cheng1, Bai-Hsiun Chen1
1Department of Laboratory Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

Tóm tắt

Enteroviruses are environmental triggers in the pathogenesis of type 1 diabetes mellitus (DM). A sequence of six identical amino acids (PEVKEK) is shared by the 2C protein of Coxsackie virus B and the glutamic acid decarboxylase (GAD) molecules. Between 1995 and 2002, we investigated 22 Coxsackie virus B5 (CVB5) isolates from southern Taiwan. Four of these isolates were obtained from four new‐onset type 1 DM patients with diabetic ketoacidosis. We compared a 300 nucleotide sequence in the 2C protein gene (p2C) in 24 CVB5 isolates (4 diabetogenic, 18 non‐diabetogenic and 2 prototype). We found 0.3‐10% nucleotide differences. In the four isolates from type 1 DM patients, there was only 2.4‐3.4% nucleotide difference, and there was only 1.7‐7.1% nucleotide difference between type 1 DM isolates and non‐diabetogenic isolates. Comparison of the nucleotide sequence between prototype virus and 22 CVB5 isolates revealed 18.4‐24.1% difference. Twenty‐one CVB5 isolates from type 1 DM and non‐type 1 DM patients contained the PEVKEK sequence, as shown by the p2C nucleotide sequence. Our data showed that the viral p2C sequence with homology with GAD is highly conserved in CVB5 isolates. There was no difference between diabetogenic and non‐diabetogenic CVB5 isolates. All four type 1 DM patients had at least one of the genetic susceptibility alleles HLA‐DR, DQA1, DQB1. Other genetic and autoimmune factors such as HLA genetic susceptibility and GAD may also play important roles in the pathogenesis in type 1 DM.

Tài liệu tham khảo

10.2337/diab.22.6.429 10.1007/BF00400925 10.1016/S0140-6736(95)91270-3 10.1007/BF00401772 Preventing insulin dependent diabetes mellitus: the environmental challenge, 1987, Diabetes Epidemiology Research International, BMJ, 295, 479 Graves PM, 1997, The role of enteroviral infections in the development of IDDM, Diabetes, 46, 161, 10.2337/diab.46.2.161 10.1056/NEJM197905243002102 10.1016/S0022-3476(82)80228-X 10.1038/274693a0 Yoon JW, 1976, Virus induced diabetes mellitus VI. Genetically determined host difference in the replication of encephalomyocarditis virus in pancreatic beta cells, J Exp Med, 143, 170 Yoon JW, 1976, Genetic difference in the susceptibility of pancreatic B cells to virus‐induced diabetes mellitus, Nature, 265, 178, 10.1038/264178a0 10.1006/viro.1994.1329 10.1038/366069a0 Peterson JS, 1994, Detection of GAD65 antibodies in diabetes and other autoimmune disease using a simple radioligand assay, Diabetes, 43, 459, 10.2337/diab.43.3.459 10.1172/JCI117567 10.1038/nm0296-148 10.1084/jem.180.2.721 10.2337/diabetes.43.10.1260 Rowley MJ, 1992, Antibodies to glutamic acid decarboxylase discriminate major types of diabetes mellitus, Diabetes, 41, 548, 10.2337/diab.41.4.548 10.1007/s001250050864 10.1111/j.1399-0039.1992.tb01940.x 10.1111/j.1399-0039.1993.tb01991.x 10.1016/0003-2697(87)90021-2 10.1128/JVI.70.6.3876-3886.1996 Adams SF, 1926, The seasonal variation in the onset of acute diabetes, Arch Intern Med, 27, 861, 10.1001/archinte.1926.00120240133010 10.1016/0168-1702(95)00055-U Glandisch R, 1976, Myocarditis and insulitis following coxsackie virus infection, Z Kardiol, 65, 837 Ginsberg‐Fellner F, 1986, The Immunology of Diabetes Mellitus, 279 Gamble DR, 1980, Relation of antecedent illness to development of diabetes in children, BMJ, 99, 10.1136/bmj.281.6233.99 10.1016/S0140-6736(79)90853-5 Chikazawa K, 1985, Acute onset of insulin‐dependent diabetes mellitus caused by Epstein‐Barr virus infection, Acta Obstet Gynaecol Jpn, 37, 1493 Jali MV, 1990, Transient diabetes following chickenpox, J Assoc Physicians India, 38, 663 Ju HS, 2001, The role of viruses in type 1 diabetes: two distinct cellular and molecular pathogenic mechanisms of virus‐induced diabetes in animals, Diabetologia, 44, 271, 10.1007/s001250051614 Chung YH, 1997, Role of macrophages and macrophage‐derived cytokines in the pathogenesis of Kilham rat virus‐induced autoimmune diabetes in diabetes‐ resistant BB rats, J Immunol, 159, 466, 10.4049/jimmunol.159.1.466 10.1016/S0168-8227(01)00272-8 10.1046/j.1365-2265.1997.2851090.x 10.3109/08916939409009539 Chen BH, 2000, The influence of age and gender on HLA‐DR in Chinese child‐onset type 1 diabetes mellitus patients, Kaohsiung J Med Sci, 16, 400 10.1016/S0198-8859(99)00106-8
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The Kaohsiung Journal of Medical Sciences

Tập 20

525-532

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