Evidence that neomycin inhibits binding of herpes simplex virus type 1 to the cellular receptor.
The effect of neomycin, a phosphoinositide-binding aminoglycoside, on herpes simplex virus type 1 (HSV-1) infection of BHK cells was studied. We showed earlier that it specifically inhibits HSV-1 production but not HSV-2 production (Langeland et al., Biochem Biophys. Res. Commun. 141:198-203, 1986). We now show that neomycin had no effect on cellular protein synthesis, as judged by the appearance of 35S-labeled polypeptides separated by polyacrylamide gel electrophoresis. Virus-induced polypeptides, however, were strongly inhibited at neomycin concentrations above 2 mM. Comparison among different aminoglycosides showed a variation in inhibition of HSV-1 production that paralleled the cationic charge of the aminoglycosides. HSV-1 receptor binding at 4 degrees C was completely inhibited by neomycin. At 37 degrees C both receptor binding and internalization, as measured by an indirect assay, appeared to be inhibited by more than 90%. The effect of neomycin on the infection was almost immediate upon the addition of the drug and preceded virus internalization. Possible mechanisms of the neomycin effect are discussed.
Langeland
N
N
Department of Biochemistry, University of Bergen, Norway.
Holmsen
H
H
Lillehaug
J R
JR
Haarr
L
L
D000818:Animals; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D005839:Gentamicins / Q000494:pharmacology; D009355:Neomycin / Q000494:pharmacology*; D011991:Receptors, Virus / Q000187:drug effects / Q000502:physiology*; D018139:Simplexvirus / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D013045:Species Specificity; D013307:Streptomycin / Q000494:pharmacology; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000378:metabolism; D014764:Viral Proteins / Q000096:biosynthesis
D005839:Gentamicins; D011991:Receptors, Virus; D014764:Viral Proteins; D013937:Thymidine Kinase; D009355:Neomycin; D013307:Streptomycin