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In silico B-cell epitope prediction: developing differential diagnosis for haemorraghic diseases caused by orthohantaviruses Orthohantaviruses are the etiological agents of serious rodent-borne neglected human diseases named as hemorrhagic fever with renal syndrome (HFRS) and orthohantavirus cardiopulmonary syndrome (HCPS). These distinct clinical manifestations of disease are related to specific orthohantavirus species and it is believed that HFRS-associated orthohantavirus mainly circulate into Old World (Asia and Europe) whereas HCPS-associated orthohantaviruses are predominant into New World countries (Americas). However, since Seoul orthohantavirus, associated with HFRS, was isolated in America and its natural host (Rattus norvegicus) are widely distributed around the world, it raised the question if the viral underreporting is associated to lower medical awareness of the symptoms or if it is associated to misdiagnosis with other tropical hemorrhagic diseases (leptospirosis, yellow fever). In this context, considering that the HFRS are clinically indistinguishable from order hemorrhagic diseases, and that serological tests are predominantly based on serology tests against nucleoprotein, a highly conserved protein among different orthohantavirus, we hypothesize that current available tests do not detect all HFRS-associated orthohantavirus. In this sense; we aimed to identify B-cell linear epitopes exclusively conserved on HFRS-associated orthohantavirus nucleoprotein, using a combination of in silico and experimental approaches, to identify targets that could be applied in the development of novel immunodiagnostic tools able to identify different HFRS orthohantavirus species.
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