Investigation into the vector competence of Ixodes ricinus ticks to Hazara virus and Crimean-Congo Haemorrhagic Fever virus

Abstract

Tick-borne pathogens represent a large threat to the UK and International Public Health authorities. Due to recent changes in legislation, an increase in animal & human movements and changing climate, the UK may now be at an increased risk of importing exotic tick species and their associated pathogens. It is vital to assess the susceptibility of UK tick species to these highly fatal tick-borne viral zoonoses. To date, studies investigating the interaction of many pathogens with their vectors have been hindered due to the lack of a suitable tick transmission model at high containment. This thesis investigates the intrinsic ability of Ixodes ricinus, the most widely distributed tick in Europe and the UK, to acquire, replicate and transmit both Hazara virus (HAZV, a hazard group 2 surrogate for CCHFV) and Crimean–Congo haemorrhagic fever virus (a hazard group 4 pathogen) addressing their potential to act as competent vectors. During the last decade CCHFV has emerged in new areas within Europe and the principle tick vector of CCHFV has been detected within the UK. The development of methods for use with ticks and highly pathogenic viruses within ticks was an essential part of this work. Firstly techniques for the handling, extraction and storage of RNA obtained from I. ricinus ticks were optimised and different endogenous controls were assessed for their ability to amplify mRNA transcripts for use as endogenous controls. The use of the immersion technique for use with I. ricinus nymphs was optimised and working procedures and protocols for handling ticks at containment level 2 and 4 were established. Ixodes ricinus nymphs are susceptible to infection with HAZV with 100% becoming infected 13 days post-immersion. HAZV was able to establish itself within the key target organs of the tick midgut and salivary glands, produce infectious virus particles and transmit virus to 38% of mice. This artificial method of inoculation was optimised for use within the CL4 environment and was used to show that I. ricinus nymphs were not susceptible to CCHFV via immersion. In addition to horizontal transmission, I. ricinus ticks also demonstrated vertical transmission of HAZV through to the adult stage. This is the first time I. ricinus ticks have been assessed for their susceptibility to HAZV and CCHFV and their use in establishing the first high containment In vivo tick feeding model in Europe.