Sequence comparison of the rodent-adapted viruses to the human MARV isolates revealed several mutations. Sixty-one nucleotide changes in the mouse-adapted RAVV Ravn variant were detected in the ORFs of NP, VP35, VP40, and VP30 (14 amino acid changes in total) or untranslated regions (VP35, VP40, GP, VP30) [130] . In a second study analyzing genome changes during mouse adaptation, 75 nucleotide changes during adaptation of RAVV Ravn and 33 changes for MARV Ci67 were described, with most amino acid changes occurring in VP40 [131] . During guinea pig adaptation, only 11 nucleotide changes were observed, resulting in four amino acid changes. One of these changes was located in VP40 and the other mutations were detected in the viral polymerase L [222] . The only amino acid exchange detected in both the mouse-and the guinea pig-adapted MARV is amino acid 184 in VP40 (Asp to Asn). This was also the first mutation detected during mouse adaptation for both RAVV Ravn and MARV Ci67, as analyzed by sequencing of serial passages [131] . This is of particular interest because VP40 has been shown to function as an inhibitor of IFN signaling (see above, 7.3. Viral Proteins, VP40) [125, 126] . Both IFN receptor-and STAT1-deficient mice develop disease using non-adapted MARV, highlighting the importance of the IFN pathway for the control of MVD [226] [227] [228] .