UBC Theses and Dissertations
A theoretical study of the entry of baculovirus into cell nucleus Vaez Ghaemi, Roza
The nucleocapsids of the baculovirus have been observed to undergo intracellular trafficking driven by actin polymerization. Propelled by an actin tail through the cytoplasm, the baculovirus nucleocapsid finds its way to the nucleus of the host cell. Then it docks to the cytoplasmic filaments of the nuclear pore complex (NPC), and manages to enter the nucleus intact. These interesting experimental observations inspired the current research. We first focus on the actin polymerization mechanism and the propulsive force generated at the back of the virus. Then, at the NPC interface, we integrate the mechanism for opening the central channel and passage of the virus. For the first part, using a microscopic approach and implementing an elastic Brownian ratchet model, we suggest a biphasic force-velocity relationship for baculovirus riding on the actin comet tail, which stalls at an external force of around 50 pN. Then, having this force value as the key parameter, we evaluate the idea of mechanical breakthrough into the NPC channel. For this purpose, we model the central channel of the NPC as saturated hydrogel. A mechanical fracture model shows that in order for the actin force to affect a purely mechanical breakthrough, the gel must be exceedingly soft. Although our results do not offer direct support for the hypothesis of a purely mechanical entry, they do not disprove the idea, either. Possibly the homogeneous hydrogel model for the NPC is inadequate, and more complex models (e.g. polymer brushes and forest) need to be examined. It is also possible that the mechanical entry of the virus is aided by biochemical signals that soften or partially remove the NPC barrier.
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