Inhibition of the antiviral action of interferon by tick salivary gland extract.

The saliva of haematophagous arthropods (e.g. mosquitoes, sandflies and ticks) contains potent immunomodulatory activities that counter their hosts' haemostatic, inflammatory and immune responses to facilitate blood-feeding. Such effects are exploited by arthropod-transmitted pathogens to promote their transmission. We investigated the ability of tick saliva to enhance arthropod-borne virus (arbovirus) transmission by determining its effect on the antiviral action of murine interferon (IFN alpha/beta). Salivary gland extract (SGE) was prepared from partially fed adult female Dermacentor reticulatus ticks that had been feeding on mice for either 3 or 5 days (SGED3 and SGED5, respectively). We demonstrated that SGE inhibits the antiviral effect of IFN as measured by a biological assay using vesicular stomatitis virus (VSV), and by two-dimensional electrophoretic analysis of the appearance of selected VSV proteins. The most pronounced effect was observed when mouse L cells were treated with SGE prior to IFN treatment. Following pretreatment with SGE, virus multiplication (which was fully blocked by IFN treatment alone) achieved yields similar to those obtained from infected cells not treated with IFN. Contemporaneous treatment, or treatment with SGE after IFN, was less effective. In parallel with these findings, formation of early viral proteins, N (nucleocapsid protein) and P (phosphoprotein), which was blocked by IFN, was detectable following pretreatment with SGE. The ability to inhibit the antiviral action of IFN was higher for SGED3 compared to SGED5. Demonstration that tick SGE can promote virus replication by suppressing the action of IFN helps explain why ticks are such efficient vectors of arboviruses.