Effect of genistein on replication of bovine herpesvirus type 1.
OBJECTIVE
To study the antiviral activity of genistein, a soya isoflavone, on in vitro replication of bovine herpesvirus type 1 (BHV-1).


METHODS
Madin-Darby bovine kidney (MDBK) cells.


METHODS
Effects of genistein on the magnitude and kinetics of inhibition of BHV-1 phosphorylation of glycoprotein E (gE) and in vitro replication of BHV-1 in MDBK cells were evaluated. Antiviral activity of genistein was compared with 2 compounds, estradiol-17beta (EST) and tamoxifen (TAM), that have estrogenic and antiestrogenic activity, respectively. High-performance liquid chromatography (HPLC) was used to determine the concentration of genistein in medium from infected and uninfected MDBK cultures.


RESULTS
Genistein reduced BHV-1, but not gE-deleted BHV-1 (BHV-1gEdelta3.1), replication by 90% at 18 hours after inoculation. This inhibition was not sustained through 24 hours after inoculation. The genistein concentration in media from MDBK cells was decreased by 40% during BHV-1 infection, compared with 16% for uninfected cells, at 24 hours after inoculation. Genistein inhibited gE phosphorylation and BHV-1 replication in a dose-dependent manner. Dosing with 25 microM genistein at 0 and 12 hours after inoculation of BHV-1 was optimal for decreasing BHV-1 replication. Estradiol-17beta EST and TAM did not affect BHV-1 replication.


CONCLUSIONS
The decrease in genistein concentration was a viral infection-dependent event. Genistein is an inhibitor of BHV-1 replication because of its ability to inhibit tyrosine kinase activity. A possible application may be for the control of BHV-1 infection in cattle by feeding soya products rich in genistein prior to or during periods of stress.
Akula
Shaw M
SM
Department of Veterinary Science, South Dakota State University, Brookings 57007, USA.
Hurley
David J
DJ
Wixon
Regina L
RL
Wang
Chungyang
C
Chase
Christopher C L
CC
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D015153:Blotting, Western / Q000662:veterinary; D002417:Cattle; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology*; D007242:Herpesvirus 1, Bovine / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology; D014759:Viral Envelope Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D014764:Viral Proteins; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C046998:bovine herpesvirus type-1 glycoproteins; D013629:Tamoxifen; D004958:Estradiol; D019833:Genistein