Tick-borne transmission of murine gammaherpesvirus 68

Herpesviruses are a large group of DNA viruses infecting mainly vertebrates. Murine gammaherpesvirus 68 (MHV68) is often used as a model in studies of the pathogenesis of clinically important human gammaherpesviruses such as Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus. This rodent virus appears to be geographically widespread; however, its natural transmission cycle is unknown. Following detection of MHV68 in field-collected ticks, including isolation of the virus from tick salivary glands and ovaries, we investigated whether MHV68 is a tick-borne virus. Uninfected Ixodes ricinus ticks were shown to acquire the virus by feeding on experimentally infected laboratory mice. The virus survived tick molting, and the molted ticks transmitted the virus to uninfected laboratory mice on which they subsequently fed. MHV68 was isolated from the tick salivary glands, consistent with transmission via tick saliva. The virus survived in ticks without loss of infectivity for at least 120 days, and subsequently was transmitted vertically from one tick generation to the next, surviving more than 500 days. Furthermore, the F1 generation (derived from F0 infected females) transmitted MHV68 to uninfected mice on which they fed, with MHV68 M3 gene transcripts detected in blood, lung, and spleen tissue of mice on which F1 nymphs and F1 adults engorged. These experimental data fulfill the transmission criteria that define an arthropod-borne virus (arbovirus), the largest biological group of viruses. Currently, African swine fever virus (ASFV) is the only DNA virus recognized as an arbovirus. Like ASFV, MHV68 showed evidence of pathogenesis in ticks. Previous studies have reported MHV68 in free-living ticks and in mammals commonly infested with I. ricinus, and neutralizing antibodies to MHV68 have been detected in large mammals (e.g., deer) including humans. Further studies are needed to determine if these reports are the result of tick-borne transmission of MHV68 in nature, and whether humans are at risk of infection

Anti-chemokine activities of ixodid ticks depend on tick species, developmental stage, and duration of feeding

Ixodid ticks require comparatively large bloodmeals for their development and survival. Blood-feeding elicits signaling events in the host leading to wound healing responses (hemostasis, inflammation, and tissue repair) and immunity. Bioactive molecules present in tick saliva sabotage these host responses at several levels. One of them is neutralization of cellular communication by binding of specific saliva molecules to cytokines that have important roles in innate and adaptive immunity. Chemokines are a subset of cytokines having chemotactic activities. We show anti-chemokine activities in salivary gland extracts (SGE) of adult Rhipicephalus appendiculatus ticks against human chemokines CXCL8, CCL2, CCL3, CCL5, and CCL11. At comparable protein concentrations, male Ixodes ricinus SGE showed activity against all the chemokines; SGE of female I. ricinus had comparatively lower levels of activity against all the chemokines but no detectable activity against CCL5 and CCL11. However, when the equivalent of a single pair of salivary glands was tested, male I. ricinus showed little or no activity against CCL3 and CCL5. No fundamental differences in activity were observed against mouse compared with human chemokines. A comparison with previously published data for Dermacentor reticulatus and Amblyomma variegatum indicates that the level of anti-cytokine activity depends on the species, developmental stage (adult or nymph), and amount of SGE used, as well as on the number of days the tick has been feeding

Ixodid tick salivary gland products target host wound healing growth factors

For successful blood-feeding, ticks must confront the host immune system comprising many cells and signaling molecules, mainly cytokines and growth factors. These factors bind to specific receptors on the cell membranes, thereby initiating a signaling cascade that leads to distinct cellular activities. Ticks are able to manipulate host immune responses via molecules secreted from their salivary glands. Saliva of ixodid ticks contains factors binding important cytokines and their subgroup, chemokines. Here we demonstrate that constituents of tick salivary gland extract (SGE) also appear to bind growth factors: transforming growth factor beta (TGF-β1), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF-2), and hepatocyte growth factor (HGF), depending on tick species. SGE derived from Amblyomma variegatum reacted with TGF-β1, PDGF, FGF-2 and HGF; Dermacentor reticulatus and Rhipicephalus appendiculatus with TGF-β1, FGF-2 and HGF; and Ixodes ricinus and Ixodes scapularis with PDGF. SGE from the species targeting PDGF (A. variegatum and I. ricinus) also inhibited cell proliferation in vitro and induced a change in morphology of different cell lines. These effects correlated with disruption of the actin cytoskeleton. Such effects were not observed with SGE of the two species that did not target PDGF. Targeting of wound healing growth factors appears to be yet another strategy ixodid ticks adopt for suppression of inflammation and successful haematophagy