Acute onset of type I diabetes mellitus after severe echovirus 9 infection: putative pathogenic pathways.
Enterovirus infections have been implicated in the development of type I diabetes mellitus. They may cause beta cell destruction either by cytolytic infection in the pancreas or indirectly by contributing to autoimmune reactivity. We sought evidence for these 2 mechanisms in a case of acute-onset diabetes mellitus that occurred during severe echovirus 9 infection. The virus was isolated and administered to cultured human beta cells. No viral proliferation was observed, and no beta cell death was induced, while parallel exposure to Coxsackie B virus serotype 3 resulted in viral proliferation and massive beta cell death. Although the viral protein 2C exhibited a sequence similar to that of the beta cell autoantigen glutamic acid decarboxylase (GAD(65)), no cross-reactive T cell responses were detected. The patient did not develop antibodies to GAD(65) either. Absence of evidence for direct cytolytic action or an indirect effect through molecular mimicry with GAD(65) in the present case raises the possibility of another indirect pathway through which enteroviruses can cause diabetes mellitus.
Vreugdenhil
G R
GR
Department of Medical Microbiology, University Hospital, Nijmegen, The Netherlands.
Schloot
N C
NC
Hoorens
A
A
Rongen
C
C
Pipeleers
D G
DG
Melchers
W J
WJ
Roep
B O
BO
Galama
J M
JM
D000208:Acute Disease; D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003429:Cross Reactions; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000276:immunology / Q000821:virology; D004459:Echovirus 9 / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D004457:Echovirus Infections / Q000150:complications* / Q000276:immunology; D029822:Enterovirus B, Human / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D005260:Female; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000276:immunology; D006801:Humans; D007223:Infant; D007515:Islets of Langerhans / Q000276:immunology / Q000821:virology; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology; D014774:Virulence
D001323:Autoantibodies; D001324:Autoantigens; D002352:Carrier Proteins; D017361:Viral Nonstructural Proteins; C076023:2C protein, viral; D005968:Glutamate Decarboxylase