Comparison of nucleotide sequence of p2C region in diabetogenic and non-diabetogenic Coxsacie virus B5 isolates.
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.
Chou
Cheng-Chong
CC
Department of Laboratory Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Lin
Kuei-Hsiang
KH
Ke
Guan-Ming
GM
Tung
Yi-Ching
YC
Chao
Mei-Chyn
MC
Cheng
Jeng-Yin
JY
Chen
Bai-Hsiun
BH
D000293:Adolescent; D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D003920:Diabetes Mellitus / Q000276:immunology / Q000821:virology*; D029822:Enterovirus B, Human / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D004769:Enterovirus Infections / Q000821:virology; D005260:Female; D006680:HLA Antigens / Q000032:analysis / Q000145:classification; D006367:HeLa Cells; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics; D012621:Seasons; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D006680:HLA Antigens; D012367:RNA, Viral