The fourth gene from the 3 end of the filovirus genome encodes the viral envelope GP (Figure 2) , which is responsible for both receptor binding and fusion of the virus envelope with the host cell membrane (Takada et al., 1997; Wool-Lewis and Bates, 1998) (Figures 3 and 4) . GP is highly glycosylated with large amounts of N-and O-linked glycans, most of which are uniformly located in the middle one-third of the GP, designated the mucin-like region (MLR) Manicassamy et al., 2007) . The amino acid sequences of the MLR are highly variable among filovirus species (Sanchez et al., 1996 (Sanchez et al., , 1998 . GP undergoes proteolytic cleavage by host proteases such as furin (Volchkov et al., 1998) , which produces two subunits, GP1 and GP2, linked by a disulfide bond. The GP1 subunit mediates viral attachment, most likely through the MLR or the putative receptor binding region (RBR; Kuhn et al., 2006; Dube et al., 2009) . The GP2 subunit has the heptad repeat regions required for assembling GP as a trimer. The hydrophobic fusion loop on GP2 is thought to catalyze fusion of the viral envelope and host cell membrane (Weissenhorn et al., 1998; Ito et al., 1999) . Although the trigger to promote the conformational change leading to membrane fusion is not fully understood, it was recently suggested that endosomal proteolysis of EBOV and MARV GPs by cysteine proteases such as cathepsins B and L plays an important role in inducing membrane fusion (Chandran et al., 2005; Schornberg et al., 2006; Matsuno et al., 2010a) . Since GP is the only viral surface GP, it is believed to have an important role in controlling the tropism and pathogenesis of filovirus infection Hoenen et al., 2006; Sanchez et al., 2007) .