The Mechanism of the Antiherpetic Activity of Zinc Sulphate

Abstract

The molecular mechanism of the effects of zinc ions against herpes simples virus (HSV) infection was investigated. Zinc sulphate (100 ~tM) in the culture medium of an HSV-infected African green monkey kidney cell line did not block viral DNA synthesis and, at this concentration, only moderate cytotoxic effects were observed in uninfected cells. Nevertheless, virus yields were reduced to less than 1%0 of the control. Thus the long standing hypothesis that zinc might block multiplication of HSV by selective intranuclear inhibition of the viral DNA polymerase apparently has lost its validity. Inhibition of virus growth in the absence of severe cytotoxicity must therefore result from other effects of ZnSO4. Free virus is inactivated by 15 mM-ZnSO4 within a few hours of its addition.The inactivated virus is defective in the glycoproteindependent functions of penetration and, to some extent, adsorption. Electron micrographs show massive deposition of zinc onto virion components. In a virion, transmembrane transport of zinc ions is not expected and the established antiviral effect is therefore explained by an inhibition of virion glycoprotein function after non-specific accumulation of zinc into many virion membrane components.

Global Impact of Influenza Virus on Cellular Pathways Is Mediated by both Replication-Dependent and -Independent Events

“…It will be extremely interesting to examine the outcome of influenza virus infection in cell lines by inducing metallothionein gene expression (by treatment with Zn or IL-6) before or after infection or in metallothionein knockout mice (44). With regard to the former, the clinical administration of Zn at the onset of illness has been shown to reduce the severity and longevity of coldlike symptoms (18,40) and has been shown to reduce herpes simplex virus infectivity in vitro (33). Nearly all of the genes regulated independently of viral replication were downregulated (82 of 97), most of them exclusively at the 4-h time point (74 of 82).…”

Virus Concentration Using Sulfonated Magnetic Beads to Improve Sensitivity in Nucleic Acid Amplification Tests

“…Since several reports suggested that divalent cations interact with viruses, [20][21][22][23][24] we expected the viruses to form complexes with divalent cations. We tried to trap the complexes of virus and divalent cation with negatively charged SO-magnetic beads.…”

“…Divalent cations, such as Cu 2ϩ or Zn 2ϩ ions, have been reported to interact with several species of viruses. [20][21][22][23][24] We, therefore, suspected that after incubation with viruses and divalent cations, the SO-magnetic beads may adsorb the complex of virus and divalent cations. The present study shows that the SO-magnetic beads adsorb many viruses, including not only Sindbis virus or SV-40, but also PPV or poliovirus.…”

“…Electron micrographs showed deposition of zinc onto the virion surface, which blocked presentation to the cell of a virion binding site. 22) Chruscinski et al 20) reported the specific interaction of Cu 2ϩ ions with fragments of envelope protein of hepatitis B virus. These data indicate that some divalent cations interact with virus surface protein or phospholipid.…”

“…Both Zn 2ϩ and Cu 2ϩ ions were reported to inactivate or interfere with many viruses. [22][23][24] Kümel et al 22) showed that Zn 2ϩ -inactivated virus cannot properly penetrate a susceptible cell because the bound Zn 2ϩ ion functionally inactivated the viral surface glycoprotein. Electron micrographs showed deposition of zinc onto the virion surface, which blocked presentation to the cell of a virion binding site.…”