Immunological cross-reactions with paramyxovirus nucleoproteins may explain sporadic apparent ebolavirus seropositivity in European populations

Although confirmed outbreaks of Ebola Virus Disease (EVD) have been confined to central and west Africa, seropositivity to Zaire ebolavirus (EBOV) has been reported in other parts of Africa and even in one study from the early 1990s in Germany. The possible reasons for the discrepancy between serological studies and clinical evidence, remain uncertain. Here, we report anonymous serum donors sampled in Lancaster (UK) with seropositivity by ELISA to EBOV nucleoprotein at a frequency of approximately 2%. In one serum donor, we confirm the result using Western blot. This is only the second report of seropositivity for EBOV outside of Africa. Our samples are negative to EBOV glycoprotein, suggesting that the seropositivity is specific to the nucleoprotein and may be due to cross-reaction with antibodies produced by exposure to another virus. To investigate potential candidates for this cross-reacting virus, we perform bioinformatics analysis that suggests that EBOV nucleoprotein has structural similarity to paramyxovirus nucleoproteins at a candidate immunological epitope. Cross-reaction of antibodies against paramyxovirus nucleoproteins, with EBOV nucleoprotein antigens used in serological testing, may be the cause of the rare instances of ebolavirus seropositivity in Europe, and may also be a confounding factor in African serosurveys.