Genetic and phenotypic diversity of echovirus 30 strains and pathogenesis of type 1 diabetes.
Several enterovirus serotypes should be considered as potentially diabetogenic. The capacity of an enterovirus to kill or impair the functions of human beta-cells can vary among the strains within a given serotype as shown previously for echovirus 9 and 30 (E-30). The evolution of E-30 has also shown patterns correlating with the global increase of type 1 diabetes incidence. In the present study, antigenic properties of a set of E-30 isolates were investigated and the results correlated with the previously documented beta-cell destructive phenotype of the strains, or to genetic clustering of the strains. No simple correlation between the three properties was observed. A full-length infectious clone was constructed and sequenced from one of the isolates found to be most destructive to beta-cells (E-30/14916net87). Phylogenetic analyses demonstrated that this strain was closely related to the E-30 prototype strain at the capsid coding region while outside the capsid region prototype strains of several other human enterovirus B serotypes clustered more closely. This suggests that the relatively greater pathogenicity of the strain might be based on properties of the genome outside of the structural protein coding region. Neutralizing antibody assays on sera from 100 type 1 diabetic patients and 100 controls using three different E-30 strains did not reveal differences between the groups. This finding does not support a previous proposition of aberrant antibody responses to E-30 in diabetic patients. It is concluded that identification of the genetic counterparts of pathogenicity of E-30 strains requires further studies.
Paananen
A
A
Enterovirus Laboratory, National Public Health Institute, Helsinki, Finland.
Savolainen-Kopra
C
C
Kaijalainen
S
S
Vaarala
O
O
Hovi
T
T
Roivainen
M
M
D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D003429:Cross Reactions; D004279:DNA, Viral / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000276:immunology / Q000821:virology*; D004457:Echovirus Infections / Q000150:complications* / Q000276:immunology / Q000821:virology*; D029822:Enterovirus B, Human / Q000145:classification / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity*; D005387:Finland; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010641:Phenotype; D010802:Phylogeny; D012703:Serotyping
D000914:Antibodies, Viral; D000956:Antigens, Viral; D004279:DNA, Viral