Epstein Barr virus nuclear antigen 1 (EBNA-1) peptides recognized by adult multiple sclerosis patient sera induce neurologic symptoms in a murine model

Abstract

Multiple sclerosis (MS) is an autoimmune demyelinating disease with progressive neurodegeneration and complex etiology likely involving genetic and environmental factors. MS has been associated with Epstein Barr virus (EBV) infection, with patients often showing enhanced responses to EBV antigens. To determine whether abnormal EBV nuclear antigen-1 (EBNA-1) humoral immunity can serve as an initiator of autoimmune responses in MS, we investigated the fine specificities of the humoral immune response against EBNA-1 in MS patients using solid phase epitope mapping. Antibodies from MS patients recognized an EBNA-1 epitope spanning amino acids 411-426, previously unknown to be recognized specifically by untreated MS patients. Antibodies against this epitope cross-reacted to myelin basic protein (MBP). Furthermore, animals immunized with this EBNA-1 polypeptide mounted a response against MBP and developed signs of experimental autoimmune encephalitis (EAE). These data support a link between MS and EBV through antibodies that cross-react between EBV proteins and the MBP autoantigen.

Viral infections and multiple sclerosis

“…Very interesting results come from a recent study showing that MS patient sera, differently from healthy controls, recognize unique EB nuclear antigen (EBNA) 411-426 epitopes with antibodies cross-reacting with myelin basic protein (MBP). Moreover SJL/J and Balb/c mice injected with EBNA 411-426 peptide develop signs of EAE [78]. Based on these findings, a new line of investigation can be developed for a further insight into the possible role of EBV through molecular mimicry in MS pathogenesis.…”

The Nerves to Conduct a Multiple Sclerosis Crime Investigation

“…Libbey et al [ 70 ] hypothesize that MS could be triggered via molecular mimicry, whereby specific peptides secreted by pathogens have sequence or structural similarities to self-antigens. Previous studies have suggested the role of molecular mimicry in the pathogenesis of MS through Haemophilus influenzae viral infections [ 71 ], and a potentially similar mechanism has been observed for EBV infection [ 72 ]. The proposed cascade of events leading to CNS autoimmunity following EBV infection involves the proliferation and maturation of T-cells against Epstein–-Barr virus nuclear antigen 1 (EBNA1) [ 73 ].…”

Autoantibodies against central nervous system antigens in a subset of B cell–dominant multiple sclerosis patients

“…Several of these antigens have structural or sequence similarities with epitopes of bacterial and viral antigens. Thus, molecular mimicry is an appealing hypothesis for the origin of autoreactivities, with EBV and human herpes virus 6 proposed as viral candidates that mimic myelin proteins (27,46,47). New bacterial candidates have been identified as molecular mimics relevant to MS from in-depth studies of the microbiome (48).…”