Effect of genistein on replication of bovine herpesvirus type 1

Shaw M. Akula Department of Veterinary Science, South Dakota State University, Brookings, SD 57007.
Present address is Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KS 66160.

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 MVSc, PhD
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David J. Hurley Departments of Veterinary Science, Biology and Microbiology, South Dakota State University, Brookings, SD 57007.
Present address is Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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Regina L. Wixon Department of Nutrition and Food Science South Dakota State University, Brookings, SD 57007.

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Chungyang Wang Department of Nutrition and Food Science South Dakota State University, Brookings, SD 57007.

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Christopher C. L. Chase Department of Veterinary Science, South Dakota State University, Brookings, SD 57007.

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Abstract

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

Sample Population—Madin-Darby bovine kidney (MDBK) cells.

Procedure—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-17β (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-1gEΔ3.1), 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 µMgenistein at 0 and 12 hours after inoculation of BHV-1 was optimal for decreasing BHV-1 replication. Estradiol-17β EST and TAM did not affect BHV-1 replication.

Conclusions and Clinical Relevance—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. (Am J Vet Res 2002;63:1124–1128)

Abstract

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

Sample Population—Madin-Darby bovine kidney (MDBK) cells.

Procedure—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-17β (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-1gEΔ3.1), 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 µMgenistein at 0 and 12 hours after inoculation of BHV-1 was optimal for decreasing BHV-1 replication. Estradiol-17β EST and TAM did not affect BHV-1 replication.

Conclusions and Clinical Relevance—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. (Am J Vet Res 2002;63:1124–1128)

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