The Guillain–Barrè peptide signatures: from Zika virus to Campylobacter, and beyond

Abstract:

Scientific attention has focused recently on the link between Guillain–Barrè syndrome (GBS) and Zika virus (ZIKV). Two related questions emerged: 1) what triggered the violent 2014 outbreak of a virus, which, first identified in 1947, had caused only a limited number of documented cases of human infection until 2007 and 2) which molecular mechanism(s) relate ZIKV active infection to GBS, an autoimmune inflammatory polyradiculoneuropathy. Capitalizing on the increased interest on ZIKV and hypothesizing the involvement of autoimmune mechanisms, we searched for minimal epitopic determinants shared between ZIKV and other GBS-related pathogens – namely, Epstein–Barr virus, human cytomegalovirus, influenza virus, Campylobacter jejuni, and Mycoplasma pneumoniae, among others – and human proteins that, when altered, have been associated with myelin disorders and axonopathies. We report a considerable peptide matching that links GBS-related pathogens to human proteins related to myelin disorders and axonopathies. Crucially, the shared pentapeptides repeatedly occur throughout numerous epitopes validated as immunopositive by a conspicuous scientific literature. The data support a scenario where multiple different infections over time and resulting multiple cross-reactions may contribute to the pathogenesis of GBS. In practice, previous infection(s) might create immunologic memory able to trigger uncontrolled hyperimmunogenicity during a successive pathogen exposure. ZIKV pandemic appears to be an exemplar model for a proof-of-concept of such multiple cross-reactivity mechanism.

Keywords::

• peptide sharing
• GBS-related human proteins
• GBS-related pathogens
• multiple cross-reactivity
• hyperimmunogenicity

Acknowledgments

GL gratefully acknowledges support from the Deutscher Akademischer Austauschdienst (DAAD), the Deutsche Forschungsgemeinschaft (DFG), and the Freie Universität Berlin, Germany. DK’s studies and research have been supported by University of Bari, Italy.

Disclosure

The authors report no conflicts of interest in this work.

Supplementary materials

Table S1 List of the 97 human proteins related to myelin, (de)myelination, and/or axonal neuropathies and sharing pentapeptides with ZIKV polyprotein (human proteins are reported by UniProt entry, a brief description of function, and aa length)

Table S2 Pentapeptide platform shared by ZIKV polyprotein and human proteins related to myelin, (de)myelination, and/or axonal neuropathies: 222 ZIKV pentapeptides (in bold) recur throughout 97 proteins (in parentheses as UniProt entry names)