3106269183

3106269183



Vesicular stomatitis virus (VSV) is an extensively studied virus for a large number of applications. Member of the Rhabdoviridae family, VSV is an enveloped virus containing a 11,161 kb single strand RN A genome of negative polarity encoding five proteins: a nucleocapsid (N), a phosphoprotein (P), a matrix (M) protein, an envelope glycoprotein (G) and a polymerase (L) (Lichty et al., 2004; Rosę and Whitt, 2001; Wagner and Hewlett, 2004). VSV is non endemic to North America and infection in humans is generally asymptomatic or may induce mild flu-like symptoms (Letchworth et al., 1999; Rosę and Whitt, 2001).

VSV M protein is the smallest but the most abundant protein with around 1800 molecules per virion (McCreedy and Lyles, 1989). Considered the key protein for assembly and budding, M is mainly found in the cytoplasm (80 %) and sometimes linked to the plasma membranę (10-20%) (Ye et al., 1994). The M protein can also be found in the nucleus (Lyles et al., 1988) where it can inhibit transcription by interacting with the RNA polymerase II TFIID complex (Ahmed and Lyles, 1998; Black et al., 1993; Ferran and Lucas-Lenard, 1997; Flood et al., 2000) and with NUP98 resulting in an inhibition of the nucleocytoplasmic transport of host mRNAs (Glodowski et al., 2002; Petersen et al., 2000). It also inhibits cellular translation (Francoeur et al., 1987) by modifying the initiation complex eIF4F through dephosphorylation of initiation factors eIF4E and 4e-BP1 (Connor and Lyles, 2002; Francoeur et al., 1987). Finally, it was also shown to participate in apoptosis induction (Desforges et al., 2002; Kopecky and Lyles, 2003a; Kopecky and Lyles, 2003b; Kopecky et al., 2001).

Triraeric VSV G is responsible for attachment to the cellular receptor and for fusion to the celi membranę. Binding to the still controversial cellular receptor induces clathrin-mediated endocytosis (Le Blanc et al., 2005; Sun et al., 2005). As the pH drops in early endosomes, G changes conformation to allow fusion between the viral envelope and the endosomal membranę (Roche et al., 2007). The pH at which G is exposed during infection will determine three different structures: the pre-fusion State occuring at pH 7,

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