The inability of Marburg virus to cause disease in ferrets is not solely linked to the virus glycoprotein.

Ebola virus (EBOV) causes lethal disease in ferrets, whereas Marburg virus (MARV) does not cause disease or result in detectable viremia. To investigate the mechanistic reasons for this difference, we first evaluated glycoprotein (GP)-mediated viral entry by infecting ferret spleen cells with recombinant vesicular stomatitis viruses pseudotyped with either MARV or EBOV GP. Interestingly, both MARV and EBOV GP-pseudotyped viruses were capable of infecting ferret spleen cells, suggesting that the lack of disease following MARV infection in ferrets is not the result of a block in virus entry. Next, we evaluated replication kinetics of authentic MARV and EBOV in ferret cell lines and demonstrated that, unlike EBOV, MARV was only capable of low levels of replication. To confirm the involvement of MARV GP in virus pathogenesis, we inoculated ferrets with a recombinant EBOV expressing MARV GP in place of EBOV GP. Infection with this virus resulted in uniformly lethal disease within 7-9 days post-infection (dpi), while MARV-inoculated animals survived until study endpoint at 14 dpi with no signs of disease or detectable viremia. Together these data suggest that the inability of MARV to cause lethal infection in ferrets is not entirely mediated by GP but may, instead, be related to a block in multiple aspects of the replication cycle.