Time-line of VSV entry and uncoating events.

<p>A model for VSV entry and uncoating based on the spatio-temporal imaging analysis of MLG and RNP from rVSV-MLG. Relevant figures from the analyses are shown in parentheses. Observed times of the events are shown in red-colored font. In the model, virions attach to the cell surface, are endocytosed and trafficked to early endosomes in a Rab5-dependent manner where low pH induces conformational changes G resulting in acidification of the virion interior (A) and subsequent fusion of the viral and endosomal membrane (B). Acidification of the virion interior has an effect on the M protein to destabilize interactions between membrane-associated M (green circles with orange borders) and the condensed RNP, which results in release of the RNP into the cytoplasm after membrane fusion (C). The bulk of M remains associated with endosomes, but begins to diffuse across the endosomal membrane after RNP release (D). A smaller fraction of M is released into the cytosol and reaches the NPCs in a microtubule and actin independent manner (E).