Poliovirus-mediated entry of pokeweed antiviral protein

Abstract

Infection of HeLa cells with poliovirus results in cell permeabilization to pokeweed antiviral protein. Cell permeabilization was dependent on the integrity of virus capsid proteins and directly proportional to the multiplicity of infection. This study demonstrates that virus adsorption is sufficient for the entry of pokeweed antiviral protein into poliovirus-infected cells.

RNase inhibition of human immunodeficiency virus infection of H9 cells.

“…It has been proposed that PAP enters the cell cytosol during viral penetration, resulting in the death of infected cells and the prevention of viral reproduction (4,8). In mammalian cell culture, PAP inhibits the replication of influenza virus (3) and poliovirus (4). Similar results have been found with plant proteins homologous to PAP, including abrin A chain (8), trichosanthin (9), and bryodin (10), that all appear to function like PAP.…”

“…In plants, PAP is safely sequestered outside of cells in the absence of virus. It has been proposed that PAP enters the cell cytosol during viral penetration, resulting in the death of infected cells and the prevention of viral reproduction (4,8). In mammalian cell culture, PAP inhibits the replication of influenza virus (3) and poliovirus (4).…”

“…Pokeweed antiviral protein (PAP), for example, inhibits viral replication in plants (1,2) and in mammalian cell culture (3,4). The mechanism of viral inhibition stems from the enzymatic deglycosylation of the 28S rRNA by PAP, inhibiting protein synthesis and causing host cell death (5)(6)(7).…”

Picornavirus inhibitors

“…The proteins are efficiently delivered into the cytoplasm shortly after addition of picornavirus to the medium. Indeed, almost 100% of the cells become permeabilized in a few minutes (Otero and Carrasco, 1987b;Lee et al, 1990), suggesting that the viral particle contains a component that not only promotes the entry of the viral nucleocapsid into the cell, but also directs other macromolecules that are not physically bound to the particles towards the cytoplasm (Figs 7 and 8).…”

“…Thus, the simple idea that enveloped animal viruses enter cells only by fusion between two membranes (Marsh and Helenius, 1989) is perhaps untenable, because such a model does not explain how the co-internalization of other macromolecules takes place (Yamaizumi et al, 1979;FitzGerald et al, 1983;Carrasco et al, 1989;Lee et al, 1990). Perhaps the proton-motive force can be used to drive the viral nucleocapsid and other macromolecules through the lipid barrier of the membrane.…”