Growth, spread, and extracellular localization of herpes simplex virus 1 in Vero cells in the presence of an anti-gD plaque inhibiting monoclonal antibody.
Evidence for a direct cell-to-cell virus transfer could be provided by an agent that inhibits plaque formation without interfering with the processes that determine plaque growth in the exit and reinfection pathway of virus transfer. We studied the process of Vero cell infection by herpes simplex virus type 1 laboratory strain F [HSV-1 (F)] in the presence of monoclonal antibody (mAb) F10, an anti gD mAb that inhibits plaque development but does not neutralize virus infectivity in the absence of complement. In virus growth curves, cell associated virus was inhibited at low (0.01) but not at high (10) MOI when all cells are simultaneously infected, showing that the target of the mAb is the process of progressive cells recruitment and not the rate of virus replication. The mAb slightly inhibited virus exit and delayed virus entry. However these two additional inhibitory activities were not responsible for inhibition of virus spread, at least at early time of infection. In fact inhibition of virus spread, as measured by reduction of infectious centers (IC) from infected monolayers, could be appreciated before the appearance of extracellular virus in control cultures. We obtained electron microscope evidence that, both in the absence and in the presence of mAb, extracellular virus was initially concentrated at the interspaces between adjacent cell membranes, with little or no virus present at free cell surfaces. At more advanced stages of infection, only virus at free cell surfaces was found. The results of the study of virus replication in the presence of the mAb confirmed the hypothesis of the existence of a pathway of virus transfer between adjacent cells independent from extracellular virus. However, no electron microscope evidence for a direct cell-to-cell virus passage or for a modification of virus transfer brought about by the plaque inhibiting mAb was obtained. Interestingly, electron microscope studies suggested a targeting of the virions to different extracellular spaces, intercellular spaces and free cell surfaces, in intact and damaged cells respectively.
Mannini-Palenzona
A
A
Costanzo
F
F
Fiorilli
M P
MP
Derenzini
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D002462:Cell Membrane / Q000648:ultrastructure / Q000821:virology; D002522:Chlorocebus aethiops; D018259:Herpesvirus 1, Human / Q000254:growth & development* / Q000276:immunology* / Q000648:ultrastructure; D008854:Microscopy, Electron; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000276:immunology*; D010948:Viral Plaque Assay; D014771:Virion / Q000648:ultrastructure
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1