Entry of the two infectious forms of vaccinia virus at the plasma membane is signaling-dependent for the IMV but not the EEV

The simpler of the two infectious forms of vaccinia virus, the intracellula r mature virus (IMV) is known to infect cells less efficiently than the ext racellular enveloped virus (EEV), which is surrounded by an additional, TGN -derived membrane. We show here that when the IMV binds HeLa cells, it acti vates a signaling cascade that is regulated by the GTPase rac1 and rhoA, ez rin, and both tyrosine and protein kinase C phosphorylation. These cascades are linked to the formation of actin and ezrin containing protrusions at t he plasma membrane that seem to be essential for the entry of IMV cores. Th e identical cores of the EEV also appear to enter at the cell surface, but surprisingly, without the need for signaling and actin/membrane rearrangeme nts. Thus, in addition to its known role in wrapping the IMV and the format ion of intracellular actin comets, the membrane of the EEV seems to have ev olved the capacity to enter cells silently, without a need for signaling.