Tick-borne viruses.

Tick-borne viruses (TBVs) belong to the largest biological group known as arboviruses with unique mode of transmission by blood-feeding arthropods (ticks, mosquitoes, sand flies, biting midges, etc.) to a susceptible vertebrate host. Taxonomically, it is a heterogenous group of vertebrate viruses found in several viral families. With only one exception, African swine fever virus, all TBVs have a RNA genome. To date, at least 160 tick-borne viruses are known, some of them pose a significant threat to human and animal health worldwide. Recently, a number of established TBVs has re-emerged and spread to new geographic locations due to the influence of anthropogenic activities and few available vaccines. Moreover, new emerging tick-borne diseases are constantly being reported. Major advances in molecular biotechnologies have led to discoveries of new TBVs and further genetic characterization of unclassified viruses resulting in changes in TBVs classification created by the International Committee for the Taxonomy of Viruses. Although TBVs spend over 95% of their life cycle within tick vectors and the role of ticks as vectors has been known for over 100 years, our knowledge about TBVs and molecular processes involved in the virus-tick interactions is scarce.

Soluble M3 proteins of murine gammaherpesviruses 68 and 72 expressed in Escherichia coli: analysis of chemokine-binding properties.

M3 protein of murine gammaherpesvirus 68 (MHV-68) was identified as a viral chemokine-binding protein 3 (vCKBP-3) capable to bind a broad spectrum of chemokines and their receptors. During both acute and latent infection MHV-68 M3 protein provides a selective advantage for the virus by inhibiting the antiviral and inflammatory response. A unique mutation Asp307Gly was identified in the M3 protein of murine gammaherpesvirus 72 (MHV-72), localized near chemokine-binding domain. Study on chemokine-binding properties of MHV-72 M3 protein purified from medium of infected cells implied reduced binding to some chemokines when compared to MHV-68 M3 protein. It was suggested that the mutation in the M3 protein might be involved in the attenuation of immune response to infection with MHV-72. Recently, Escherichia coli cells were used to prepare native recombinant M3 proteins of murine gammaherpesviruses 68 and 72 (Pancík et al., 2013). In this study, we assessed the chemokine-binding properties of three M3 proteins prepared in E. coli Rosetta-gami 2 (DE3) cells, the full length M3 protein of both MHV-68 and MHV-72 and MHV-68 M3 protein truncated in the signal sequence (the first 24 aa). They all displayed binding activity to human chemokines CCL5 (RANTES), CXCL8 (IL-8), and CCL3 (MIP-1α). The truncated MHV-68 M3 protein had more than twenty times reduced binding activity to CCL5, but only about five and three times reduced binding to CXCL8 and CCL3 when compared to its full length counterpart. Binding of the full length MHV-72 M3 protein to all chemokines was reduced when compared to MHV-68 M3 protein. Its binding to CCL5 and CCL3 was reduced over ten and seven times. However, its binding to CXCL8 was only slightly reduced (64.8 vs 91.8%). These data implied the significance of the signal sequence and also of a single mutation (at aa 307) for efficient M3 protein binding to some chemokines.

Antiplatelet-derived growth factor (PDGF) activity in the saliva of ixodid ticks is linked with their long mouthparts.

The saliva of blood-feeding arthropods modulates their vertebrate hosts' haemostatic, inflammatory and immune responses to facilitate blood feeding. In a previous study, we showed that salivary gland products from ixodid tick species also manipulate the wound-healing response by targeting at least four different mammalian growth factors: transforming growth factor ß1, hepatocyte growth factor, fibroblast growth factor 2 and platelet-derived growth factor (PDGF). In addition, species that showed PDGF-binding activity also inhibited cell proliferation in vitro and induced changes in cell morphology accompanied by disruption of the actin cytoskeleton. Here, we show a correlation between the length of the tick hypostome, the sclerotized feeding tube of the mouthparts inserted into the host's skin and anti-PDGF activity. This apparent link between hypostome length, and hence the potential depth of skin damage, and PDGF-binding activity was not apparent for the other growth factors or for other cytokines important in wound healing (keratinocyte growth factor, interleukin 6 and stromal cell-derived factor 1). However, PDGF-binding activity was no longer correlated with anti-cell activities, indicating that an additional as yet unidentified activity in tick saliva may affect cellular changes in wound repair.

Immunomodulators in tick saliva and their benefits.

Ticks are significant bloodsucking ectoparasites. Apart from causing blood loss and host skin damage, ticks are important vectors of tick-borne pathogens that cause disease in humans and animals as well as significant economic loss. For biological success, ticks evolved these substances with immunomodulatory activities capable of inhibiting host defence reactions (haemostasis, inflammation and immunity reactions), and which have a radical significance for their survival. The resulting feeding site represents a favourable environment and many pathogens began exploiting ticks to facilitate their transmission to the host. The structural-functional relationships of some salivary compounds have been outlined; however research on tick sialomas indicates that further extensive exploration is required on the subject. Also, tick saliva is a complex pharmacological component with great therapeutic potential for the treatment for some diseases.