At least 38 viral species are transmitted by ticks. Virus–tick–vertebrate host relationships are highly specific and less than 10% of all tick species (Argasidae and Ixodidae) are known to play a role as vectors of arboviruses. However, a few tick species transmit several (e.g.Ixodes ricinus,Amblyomma variegatum) or many (I. uriae) tick-borne viruses. Tick-borne viruses are found in six different virus families (Asfarviridae, Reoviridae, Rhabdoviridae, Orthomyxoviridae, Bunyaviridae, Flaviviridae) and at least 9 genera. Some as yet unassigned tick-borne viruses may belong to a seventh family, theArenaviridae. With only one exception (African swine fever virus, family Asfarviridae) all tick-borne viruses (as well as all other arboviruses) are RNA viruses. Tick-borne viruses are found in all the RNA virus families in which insect-borne members are found, with the exception of the family Togaviridae. Some tick-borne viruses pose a significant threat to the health of humans (Tick-borne encephalitis virus,Crimean-Congo haemorrhagic fever virus) or livestock (African swine fever virus,Nairobi sheep disease virus). Key challenges are to determine the molecular adaptations that allow tick-borne viruses to infect and replicate in both tick and vertebrate cells, and to identify the principal ecological determinants of tick-borne virus survival.

The skin site at which ticks attach to their hosts to feed is the critical interface between the tick and its host, and tick-borne pathogens. This site is highly modified by the pharmacologically active molecules secreted in tick saliva. For pathogens, it is an ecologically privileged niche that many exploit. Such exploitation is referred to as saliva-activated transmission (SAT) – the indirect promotion of tick-borne pathogen transmission via the actions of bioactive tick saliva molecules on the vertebrate host. Here we review evidence for SAT and consider what are the most likely candidates for SAT factors among the tick pharmacopoeia of anti-haemostatic, anti-inflammatory and immunomodulatory molecules identified to date. SAT factors appear to differ for different pathogens and tick vector species, and possibly even depend on the vertebrate host species. Most likely we are searching for a suite of molecules that act together to overcome the redundancy in host response mechanisms. Whatever they turn out to be, the quest to identify the tick molecules that mediate SAT is an exciting one, and offers new insights to controlling ticks and tick-borne diseases.