Penetration of cells by herpes simplex virus does not require a low pH-dependent endocytic pathway.
Agents that perturb endocytosis or that alter the pH of endosomes were shown to have little or no effect on plaque formation by herpes simplex virus (HSV), whereas plaque formation by vesicular stomatitis virus was inhibited as expected. A number of agents were tested for their ability to inhibit early events in HSV infection. Amantadine, chloroquine and trifluoperazine, whose actions are known to alter the endocytic pathway, showed no selective inhibitory effects on early events in HSV infection. Wheat germ agglutinin and heparin, known inhibitors of HSV infection, blocked the adsorption of virus to cells, as expected. Succinylated concanavalin A blocked plaque formation without inhibiting virus adsorption but could enhance the elution of bound virus. To a greater or lesser extent, succinylated concanavalin A, dithiothreitol, colchicine, monensin and cytochalasin B all inhibited or reduced the rate of events subsequent to adsorption and prior to early viral protein synthesis. Evidence is presented to suggest that each of these agents has a different mode of action. On the basis of these results and others, we conclude that endocytosis is probably not required for infection by HSV (at least not the low pH-dependent endocytic pathway) and that events occurring at the cell surface trigger virion-cell fusion leading to infection.
Wittels
M
M
Department of Molecular Genetics and Cell Biology, University of Chicago, Illinois.
Spear
P G
PG
D000327:Adsorption / Q000187:drug effects; D000547:Amantadine / Q000494:pharmacology; D000818:Animals; D002738:Chloroquine / Q000494:pharmacology; D003078:Colchicine / Q000494:pharmacology; D003208:Concanavalin A / Q000031:analogs & derivatives / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008854:Microscopy, Electron; D008985:Monensin / Q000494:pharmacology; D018139:Simplexvirus / Q000187:drug effects / Q000502:physiology*; D014268:Trifluoperazine / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014709:Vero Cells; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects / Q000502:physiology; D010948:Viral Plaque Assay; D014909:Wheat Germ Agglutinins / Q000494:pharmacology
D014909:Wheat Germ Agglutinins; D003208:Concanavalin A; D014268:Trifluoperazine; D003571:Cytochalasin B; C019558:succinylconcanavalin A; D002738:Chloroquine; D006493:Heparin; D008985:Monensin; D000547:Amantadine; D003078:Colchicine; D004229:Dithiothreitol