The Glycoprotein Mucin-Like Domain (MLD) in the Zaire ebolavirus (EBOV) may be responsible for the manifestations of Post-Ebola Virus Disease Syndrome (PEVDS)

The incidence of various ocular, CNS, and musculoskeletal complaints in the convalescent period following recovery from Ebola Virus Disease (PEVDS) has become an intense area of interest in the aftermath of the recent West Africa outbreak 2014-2015. A review of past outbreaks involving EBOV, SUDV, TAFV, and BDBV revealed similar, but poorly documented symptoms in the convalescent period. Additionally, viable virus has been identified in the recovery phase in sperm and ocular fluid up to 9 months after recovery with no evidence of viremia. A prior study by Yang in 2000 demonstrated the mucin-like domain was responsible for the vascular permeability and inflammation seen in EVD with Zaire ebolavirus infections but not in Reston ebolavirus infections. To study the mucin-like domain further, a comparative multi-sequence amino acid analysis of the poorly conserved MLD was performed and all 16 B-cell epitopes previously identified comparing all virulent species of Ebolavirus against RESTV was used to identify regions that could explain the differential virulence and vascular access to regions of immune privileged regions. Within the E1 epitope (301-316) of the MLD, the charged motif R (X1) EELSF demonstrated significant homology (86%) within the virulent species but poorly conserved in RESTV (25%). In E5-E8, charged tandem grouping of charged residues in the motif Glu-336, Asp-337, and His-338 of EBOV were conserved as to charge in the virulent group but these charged residues were replaced by the uncharged Pro-336, Thr-337, and Arg-338 in the RESTV sequence. The C-terminus GLINT motif in epitope E16 of the MLD at the GP2 junction was moderately conserved between all species including RESTV and therefore not felt to contribute to the overall differential virulence. Within the MHC class I predictions, there did not appear to be a statistically significant difference between the virulent species and RESTV. However, the MHC Class II predicted epitopes did identify a statistically significant difference between the virulent species and RESTV. Three epitopes of acceptable binding affinities in the virulent group were significantly different from RESTV (p>.05) This study suggests that the residues located within the B-cell E1 epitope (301-316) and three MHC Class II epitopes may be responsible for vascular access to these immune privileged site and persistent symptoms observed in the convalescent PEVDS. Further studies are required into the potential role of VP40 in viral persistence and reemergence within these immune privileged areas; therefore potentially provide a therapeutic strategy in PEVDS and viral persistence associated with reemergence.