Tromantadine inhibits a late step in herpes simplex virus type 1 replication and syncytium formation.
Addition of tromantadine after virus penetration inhibited HSV-1 induced syncytium formation and virus production in HEp-2 and VERO cells and acted additively with neutralizing antibody in blocking virus spread and cytopathology. Inhibition of syncytium formation in VERO cells infected with 0.01 pfu/cell of HSV-1 GC+ was observed at a concentration greater than 25 micrograms/ml. The extent of inhibition was dependent upon the multiplicity of infection and cell type. Tromantadine inhibited a late event in HSV-1 replication which appeared to be sensitive to cycloheximide. Reversal of the inhibitory effect of tromantadine on syncytium formation required new protein synthesis. HSV-1 gB, gC, and gD were synthesized in the presence of tromantadine and could be detected on the cell surface by immunofluorescence. Tromantadine most likely inhibits a cellular process that is required for syncytium formation, such as glycoprotein processing, which occurs after the synthesis of the fusion protein but before its expression on the cell surface.
Ickes
D E
DE
N.E. Ohio Universities College of Medicine, Rootstown 44272.
Venetta
T M
TM
Phonphok
Y
Y
Rosenthal
K S
KS
D000547:Amantadine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D003513:Cycloheximide / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D015726:Giant Cells / Q000187:drug effects*; D006023:Glycoproteins / Q000096:biosynthesis; D008565:Membrane Proteins / Q000096:biosynthesis; D009500:Neutralization Tests; D011817:Rabbits; D018139:Simplexvirus / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects*
D000914:Antibodies, Viral; D006023:Glycoproteins; D008565:Membrane Proteins; D014759:Viral Envelope Proteins; D003513:Cycloheximide; D000547:Amantadine; C004279:tromantadine