Picornavirus proteins share antigenic determinants with heat shock proteins 60/65

Abstract

Immunological cross-reactions between enteroviruses and islet cell autoantigens have been suggested to play a role in the etiopathogenesis of insulin dependent diabetes mellitus (IDDM). In the nonobese diabetic mouse, an autoimmune model of IDDM, one of the reactive beta cell autoantigens is the heat shock protein 60 (HSP60). These studies were prompted by sequence homology discovered between the immunogenic region in HSP60 and two regions in enterovirus capsid proteins, one in the VP1 protein and the other in the VP0, the precursor of VP2 and VP4 proteins. Possible immunological cross-reactions between enterovirus proteins and heat shock proteins were studied by EIA 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 and there is a striking degree of homology between bacterial and human heat shock proteins. Rabbit antibodies to HSP65 of Mycobacterium bovis that reacted with human HSP60 were also found to recognise capsid protein VP1 of coxsackievirus A9, VP1, and/or VP2 of coxsackievirus B4. Both viruses were also recognised by antisera raised against HSP60 of Chlamydia pneumoniae. In addition 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; antisera 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 autoantigen glutamic acid decarboxylase, there are other motifs in picornavirus proteins homologous to islet cell autoantigens, which might induce cross-reacting immune responses during picornavirus infections.

The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes

“…Polyclonal antisera raised against enteroviruses have been shown to cross react with heat shock protein (hsp)-60 [25] and the tyrosine phosphatase, IA-2 [26]. However, it seems unlikely that the Dako vp-1 antiserum recognised either of these proteins in the beta cells in this study.…”

Analysis of pancreas tissue in a child positive for islet cell antibodies

“…Even though its specificity has been demonstrated in these studies, it has also been shown that antibodies against enterovirus VP1 protein may cross-react with heat shock proteins, especially HSP60 [27]. We studied possible crossreaction by staining the tissue sample using HSP60-specific antibody.…”

Molecular Analysis of an Echovirus 3 Strain Isolated from an Individual Concurrently with Appearance of Islet Cell and IA-2 Autoantibodies

“…CBV4 and E9 strains isolated in this way have been studied, and attempts to identify diabetic determinants have been made (21,37,48,52). Other studies have identified sequences in enteroviruses that could be involved in autoimmunity through molecular mimicry (13,14,36,53). Recently, enterovirus RNA has been demonstrated in islet cells of some diabetic patients, and these cells were shown to express several receptors recognized by enteroviruses (55).…”