Thesis (PhD)-- Stellenbosch University, 2013. / ENGLISH ABSTRACT: The emergence and re-emergence of viral human pathogens from wildlife sources in the recent past has led to increased studies and surveillance of wildlife for potentially zoonotic agents in order to gain a better understanding of the pathogens, their sources as well as events that may lead to viral emergence. Of the >1407 known human pathogens, 13% are classified as emerging or re-emerging, and 58% as zoonotic; 37% of the (re-)emerging and 19% of the zoonotic pathogens are RNA viruses, accounting for the majority of recently emerged infectious diseases with a zoonotic origin, such as HIV, Ebola, Hendra, Nipah, Influenza and SARS. This study focusses on potentially zoonotic viruses hosted by rodents (Muridae family), shrews (order previously known as Insectivora/Soricomorpha, now reclassified as Eulipotyphla) and bats (order Chiroptera). Rodents and bats represent the largest (~40%) and second largest (~25%) mammalian orders and both occur on every continent except Antarctica. Together, the three mammalian orders investigated represent the most relevant potential sources of new zoonoses. In this study I investigated the occurrence of astroviruses, arenaviruses, coronaviruses and hantaviruses in South African small mammal species belonging to the orders mentioned above. These viruses have either been implicated in recent emerging zoonotic events or are considered to have the potential to cause cross-species transmissions resulting in a zoonotic event. In the first part of the study specimens collected from various bat, rodent and shrew species were screened for viral sequences by broadly reactive PCRs; positive samples were characterised by sequencing and sequence analysis. A separate part of the study focussed on hantavirus disease in humans: a seroprevalance survey was conducted to determine the presence of hantavirus antibodies in the local population. Additionally, acutely ill patients with potential hantavirus disease were tested in an attempt to identify possible acute infections and define clinical hantavirus disease in South Africa. Screening of rodent and shrew specimens resulted in the identification of eight novel arenavirus sequences. Seven of the sequences are related to Merino Walk virus, a recently identified South African arenavirus, and the eighth sequence represents a novel lineage of Old World arenaviruses. Screening of bat specimens resulted in the identification of highly diverse novel astrovirus and coronavirus sequences in various South African bat species, including the identification of a viral sequence closely related to the recently emerged Middle East Respiratory Syndrome coronavirus. While the study did not identify hantavirus infections in any of the acutely ill patients, it found seroprevalences similar to those observed in Europe and West Africa. The results obtained highlight the importance of small mammals in the emergence of potential zoonoses and further reinforce the importance of viral surveillance of relevant wildlife species. Further in-depth studies of naturally infected reservoir host populations are required in order to gain a better understanding of virus-host dynamics and the events that lead to virus emergence. / German Research Foundation (DFG) (project number: KR1293/9-1/13-1) / The Polio Research Foundation and the NHLS Research / Harry Crossley Foundation, the Polio Research Foundation and Stellenbosch University for granting scholarships and bursaries for PhD.

Indiana University-Purdue University Indianapolis (IUPUI) / Assessments of delay discounting in rodent lines bidirectionally selected for home cage intake and preference of alcohol have had mixed findings. The current study sought to examine if delay discounting related differentially to alcohol seeking versus and alcohol drinking, two processes underlying alcohol intake and preference. Three strains of rats were utilized to answer this question Long Evans (LE), high alcohol drinking rats (HAD2), and alcohol preferring P rats. All strains were compared in an adjusting amount delay discounting task. Operant self-administration of alcohol was then assessed in the sipper tube model, and finally home cage drinking was assessed in a 24 hour 2 bottle choice paradigm. In the delay discounting it was found that the P rats were steeper discounters than both the LE and HAD2. In the sipper tube model, P rats displayed higher levels of seeking than both the HAD2s and the LE, but both the P rats and the HAD2s had higher intakes than the LE. During 24 hour home cage access, the P rats and the HAD2s had higher intake and preference for alcohol than the LE, but were not different from each other. These results show that increased discounting of delayed rewards tracks with appetitive processes versus consummatory factors and home cage intake of alcohol. This builds on prior findings using selected line pairs by providing an explanation for discordant results, and supports the hypotheses that increased delay discounting is an intermediate phenotype that predisposes individuals to alcohol use disorders.