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

Abstract

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.

Tick salivary gland extract-activated transmission of Borrelia afzelii spirochaetes

“…An accelerating effect of tick SGE on the replication of vesicular stomatitis virus in murine L cells (Hajnická et al 1998) was apparently connected with the paralysis of interferon antiviral action (Hajnická et al 2000). Similarly, a mosquito feeding-induced enhancement of Cache Valley virus infection in mice was reported (Edwards et al 1998).…”

“…The inhibitory effect of tick saliva on the production of nitric oxide by macrophages has also been demonstrated (Urioste et al 1994). More recently, inhibition of NK cell activity (Kubeš et al 1994), inhibition of the antiviral action of interferon (Hajnická et al 2000), histamine-binding capacity (Paesen et al 1999) and immunoglobulinbinding capacity (Wang and Nuttall 1995) of tick saliva have been reported.…”

Roles of neutrophil β2 integrins in kinetics of bacteremia, extravasation, and tick acquisition of Anaplasma phagocytophila in mice

“…However, specific evaluation of leukocyte migration to tick-feeding sites has received little attention. Proteins within tick saliva inhibit activation of the alternative complement pathway, 20,21 interferon (IFN-␣, -␤, and -␥) production, 22,23 Th1 cytokine production, [24][25][26] and phagocyte nitric oxide and superoxide production. [27][28][29] A phagocytophila is transmitted and acquired by a tick vector, and tick saliva represents a novel stimulus for evaluation of neutrophil migration and pathogen transmission.…”

Tick Salivary Gland Extract Inhibits Killing ofBorrelia afzeliiSpirochetes by Mouse Macrophages

“…Tick saliva or salivary gland extracts (SGE) inhibited activation of the alternative pathway of complement (15) and prevented phagocytosis and other functions of neutrophils (17). The inhibitory effect of tick SGE on NK cells (8,10) and interferon (6) has been reported. Recently, histamine-binding proteins have been identified in the saliva of ixodid tick species (14).…”