Immunological cross-reactions between enteroviruses and islet cell autoanti
gens have been suggested to play a role in the etiopathogenesis of insulin
dependent diabetes mellitus (IDDM). In the nonobese diabetic mouse, an auto
immune model of IDDM, one of the reactive beta cell autoantigens is the hea
t shock protein 60 (HSP60). These studies were prompted by sequence homolog
y discovered between the immunogenic region in HSP60 and two regions in ent
erovirus capsid proteins, one in the VP1 protein and the other in the VP0,
the precursor of VP2 and VP4 proteins. Possible immunological cross-reactio
ns between enterovirus proteins and heat shock proteins were studied by E1A
and immunoblotting by using purified virus preparations, viral expression
proteins VP1 and VP0, and recombinant HSP60/65 proteins, and corresponding
polyclonal antisera. The HSP60/65 family of proteins is highly conserved an
d there is a striking degree of homology between bacterial and human heat s
hock proteins. Rabbit antibodies to HSP65 of Mycobacterium bovis that react
ed with human HSP60 were also found to recognise capsid protein VP1 of coxs
ackievirus A9, VP1, and/or VP2 of coxsackievirus B4. Both viruses were also
recognised by antisera raised against HSP60 of Chlamydia pneumoniae. In ad
dition to the capsid proteins derived from native virions, antisera to both
bacterial HSP proteins recognised expression protein VP1 of coxsackievirus
A9. The cross-reactivity was also demonstrated the other way around; antis
era to purified virus particles reacted with the HSP 60/65 proteins to some
extent. These results suggest that apart from the well-documented sequence
homology between the 2C protein of coxsackieviruses and the beta-cell auto
antigen glutamic acid decarboxylase, there are other motifs in picornavirus
proteins homologous to islet cell autoantigens, which might induce cross-r
eacting immune responses during picornavirus infections. J. Med. Virol. 62:
383-391, 2000. (C) 2000 Wiley-Liss, Inc.