Simian Virus 40 Late Proteins Possess Lytic Properties That Render Them Capable of Permeabilizing Cellular Membranes

Abstract

Many nonenveloped viruses have evolved an infectious cycle that culminates in the lysis or permeabilization of the host to enable viral release. How these viruses initiate the lytic event is largely unknown. Here, we demonstrated that the simian virus 40 progeny accumulated at the nuclear envelope prior to the permeabilization of the nuclear, endoplasmic reticulum, and plasma membranes at a time which corresponded with the release of the progeny. The permeabilization of these cellular membranes temporally correlated with late protein expression and was not observed upon the inhibition of their synthesis. To address whether one or more of the late proteins possessed an inherent capacity to induce membrane permeabilization, we examined the permeability of Escherichia coli that separately expressed the late proteins. VP2 and VP3, but not VP1, caused the permeabilization of bacterial membranes. Additionally, VP3 expression resulted in bacterial cell lysis. These findings demonstrate that VP3 possesses an inherent lytic property that is independent of eukaryotic signaling or cell death pathways.

Role of Cell-Type-Specific Endoplasmic Reticulum-Associated Degradation in Polyomavirus Trafficking

“…One interesting thing to consider is the hydrophobic nature of the minor capsid proteins. Both VP2 and VP3 of SV40 have been previously shown to have membrane lytic properties and to be able to at least partially insert into ER membranes (37). If the virion can penetrate the ER membrane to enter the cytosol, then it is reasonable to believe that it may also be able to penetrate the inner nuclear membrane to gain direct access to the nucleus.…”

A Chaperone-Activated Nonenveloped Virus Perforates the Physiologically Relevant Endoplasmic Reticulum Membrane

“…The SV40 minor structural proteins VP2 and VP3 are necessary for infection and, when translated in vitro, are capable of binding to and integrating into the ER membrane (7). These proteins also demonstrate lytic properties when expressed in Escherichia coli cells, rendering the bacterial membrane permeable to the protein synthesis inhibitor hygromycin B and, in the case of VP3 only, inducing lysis of the bacterial cells (6). These findings suggest that VP2 and VP3 might play a role in ER penetration during SV40 infection.…”

JC Virus Minor Capsid Proteins Vp2 and Vp3 Are Essential for Virus Propagation

“…This overactivation of poly(ADP-ribose) polymerase is thought to deplete intracellular ATP and cause necrosis, thereby releasing the virus (9, 10). The SV40 minor proteins have also been shown to contain lytic properties in bacteria that could aid in virus release from the cell (6).…”