The flavivirus genus is of major concern for world morbidity and mortality and includes viruses causing both encephalitic as well as hemorrhagic diseases. The incidence of Tick-borne encephalitis is increasing in many European countries and several reports have emphasized the expansion of the main vector, Ixodes ricinus. The pattern of vector distribution is also changing in Sweden, which makes it important to set up solid and successful strategies for detection and genetic characterization of novel Swedish TBEV strains. In this study we have generated strategies for detection of broad types of tick-borne flaviviruses in pools of I. ricinus sampled in Sweden. The positive collection on the island of Torö was used to generate a sequence of a complete TBEV genome straight from the arthropod reservoir. This cloned virus was used to construct a self-replicating DNA based sub-genomic TBEV replicon capable of expressing reporter genes. The replicon was used to study the effect of TBEV on neurite outgrowth, which revealed that the MTase domain of NS5 block the formation of the Scribble/Rac1/βPIX protein complex, impairing neurite outgrowth in neuronal growth factor induced PC12 cells. We also demonstrate that TBEV replication is affected by two PDZ binding motifs within NS5 and reveal putative PDZ binding proteins. These interactions might affect cellular pathways and might have a role in flavivirus replication. We also characterize the variable 3´ non-coding region (V3’-NCR) by in silico studies on TBEV. Analysis brings new evidence that V3’-NCR region carries an enhancer element important for different replication/translation dynamics during the viral lifecycle in mammalian and tick cells. We also propose a temperature-sensitive trans-acting riboswitch mechanism; altering the secondary RNA structures of a closed form at lower temperatures and a form open for translation at higher temperatures. This mechanism may explain the low TBEV level observed in sampled ticks. / <p>At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.</p>

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Thesis (Ph.D.)--Murdoch University, 2007. / Thesis submitted to the Division of Health Sciences. Includes bibliographical references (leaves 145-189).

AN ABSTRACT OF THE DISSERTATION OF Wendi Krista Middleton, for the Doctor of Philosophy degree in Health Education, presented on April 15, 2015 at Southern Illinois University Carbondale TITLE: TICK-BORNE DISEASES: ASSESSING THE KNOWLEDGE, ATTITUDES, AND BEHAVIORS OF COLLEGE STUDENTS. MAJOR PROFESSOR: Dr. Dhitinut Ratnapradipa Within the last few decades, the prevalence of tick-borne diseases (TBDs) has dramatically increased. Symptoms of TBDs are very similar to other illnesses and are often referred to as flu-like in nature. TBDs could be easily prevented, however, if people used proper prevention methods. If not treated early in the course of illness, tick-borne infections have the potential to cause serious health problems and even death. It is, therefore, extremely important that individuals use proper prevention strategies in order to reduce the risk of contracting TBDs. This research focused on the college population because these individuals represent one of the most active adult outdoor populations. While many students know that ticks carry diseases, it is thought that they have a poor understanding of the extent to which TBDs affect human health. Additionally, many experts believe that knowledge of health-related topics plays a major role in determining how individuals behave in regard to those concerns. Furthermore, a person's behavior strongly influences their risk of contracting a TBD. Information collected allowed for determining whether or not a person's knowledge and perceptions of tick-borne diseases have an influence on their prevention practices. As expected there was a lack of knowledge regarding tick-borne diseases. College students who volunteered to participate in this study indicated that they are unaware of the proper methods to use in order to prevent contracting TBDs. Thus, it was not surprising that they do not utilize correct prevention strategies. Additionally these students stated that more information about TBDs should be added to the curricula in college health courses. This research aimed to improve the psychometric properties of a newly created survey and assess college students' knowledge, attitudes, and associated behaviors regarding TBDs. Discovering the current knowledge of college students regarding TBDs has helped researchers in determining the effect that individual knowledge of TBDs has on a person's attitudes, and behaviors regarding prevention.

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Powassan (POW) virus, the cause of human encephalitis in the northeastern U.S. and Canada, is transmitted by tick bite. Since the geographic and host distribution patterns of Ixodes dammini Spielman, et al, 1979 and POW virus overlap, the potential of this tick species to transmit POW virus was explored. Transmission experiments were conducted with hamsters and rabbits which fed immature and adult ticks, respectively, from a POW-free colony. Oral infection rates in larvae and nymphs fed on POW-infected hamsters were 10% and 40%, respectively; in females fed on POW-infected rabbits, 57%. Transstadial transmission rates for nymphs exposed to POW virus as larvae, adults exposed as larvae, and adults exposed as nymphs, were 9.5%, 10% and 54%, respectively. Evidence of transovarial transmission was acquired when 2 clean hamsters feeding F$ sb2$ larvae and nymphs originally exposed to virus in the F$ sb1$ nymphal stage seroconverted to POW virus with hemagglutination inhibition titers of 80 and 5120, respectively, on week 4 post-tick-drop-off. The transovarial transmission rate was 16.6%. All developmental stages were able to transmit POW virus orally to clean hosts regardless of when the ticks were originally exposed to virus. / These results indicate that I. dammini is a competent vector of POW virus under experimental conditions. Field studies are necessary to determine if the same holds true under natural conditions.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 5 uppsatser.

Thesis (MMedVet (Med) (Small Animals))--University of Pretoria, 2007. / Includes bibliographical references.

Thesis (PhD. (Veterinary Science))--University of Pretoria, 2008. / Includes bibliographical references. Also available in print format.