(37f) M2-Mediated Influenza Virus Budding and Scission: From Basic Principles to Control

Viral release of influenza is believed to occur independently of the usual cellular machinery of endosomal sorting complexes required for transport (ESCRT); instead, scission of the extruding bud is facilitated by the M2 protein.[1] The shape of the M2 transmembrane domain is distinctly conical and the assumed mechanism by which scission proceeds is that M2 aggregates in the budding neck to cause constriction that eventually pinches off the enveloped virus.

To investigate this hypothesis, we have constructed a minimal physical model consisting of a coarse-grained lipid bilayer membrane[2] whose geometry is shaped to a budding neck by an analogue of the viral particle contents. In this way, we can model the fascinating phenomenon of budding in a generic, physiologically inspired theoretical framework on the relevant in vivo length scale. Our model is used to delineate molecular mechanisms in enveloped virus release and predict M2 aggregate topologies in various representative stages of the budding process, allowing us to propose novel antiviral strategies.

REFERENCES

[1] Rossman et al. Cell 141, pp. 902-913, 2010

[2] Brannigan et al. Phys. Rev. E 72, 011915, 2005