It has been shown that laboratory animals, including mice and guinea pigs, are susceptible to filovirus infection. However, these animals infected with filoviruses obtained from patients normally develop a non-lethal illness, though the viruses have the ability to replicate in the animals. Guinea pigs have been used as an animal model for filovirus infection since serial passage of MARV and EBOV in the animals results in a substantial increase in lethality (Bowen et al., 1980; Hevey et al., 1997; Volchkov et al., 2000; Subbotina et al., 2010) . It was also demonstrated that passages of ZEBOV through young mice resulted in the selection of variants with pathogenicity associated with mutations in viral internal genes (e.g., NP and VP40) (Bray et al., 1998; Ebihara et al., 2006) . This mouse-adapted ZEBOV is highly lethal to mice. Similarly, a mouse model for MARV infection has been established (Warfield et al., 2009) . Interestingly, mutations found in the GP gene of these mouse-or guinea pig-adapted viruses were not the primary factor for efficient replication in mice and guinea pigs, suggesting the importance of some other mechanisms underlying in viral replication and/or immune evasion, as shown in the pathogenesis of influenza virus (Fukuyama and Kawaoka, 2011) .