Rabies, one of the oldest recognized viral zoonotic diseases, is a fatal encephalomyelitis transmitted to man via contact with infected animals. Evan today, rabies still is a disease of public health concern with many potentially preventable deaths occurring mainly in Asia, Africa and Latin America. Rabies and rabies-related viruses are members of the Lyssavirus genus, which comprises the rabies virus (genotype 1), Lagos bat virus (genotype 2), Mokola virus (genotype 3), Duvenhage virus (genotype 4), European bat lyssaviruses 1 and 2 (genotypes 5 and 6) and the Australian bat lyssavirus (genotype 7). Antigenic and genetic studies have shown that rabies virus strains circulating in particular host species tend to undergo genetic adaptation and evolve into distinct biotypes that differ in antigenicity and pathogenicity. Two biotypes of rabies virus are recognized in southern Africa. The first called the canid viruses, infect carnivores of the family Canidae (dogs, jackals and bat-eared foxes) and the second, the viverrid viruses, infect carnivores of the family Herpestidae (the yellow mongoose Cynictis penicil!ata and the slender mongoose Galerella sanguinea). In an endeavour to better understand the molecular epidemiology of lyssaviruses in Zimbabwe and South Africa, we analysed nucleotide sequences of the glycoprotein and the G-L intergenic region (rabies viruses) and the nucleoprotein gene (Mokola viruses). The main aim of the studies described in this thesis was to characterise lyssaviruses (genotypes I and 3) from Zimbabwe and compare them to those present in South Africa. In addition, we wanted to establish the role of the various rabies variants in rabies epizootics in the southern African subcontinent. It could be shown from this study that all the southern African canid viruses were closely related, with no general distinction between viruses from any of the canid species. Despite the general overall similarity between the canid viruses, certain phylogenetic groupings were apparent and by association with host species, geography and year of isolation, certain groups could be identified as particular epidemiological cycles. A high genetic diversity was evident amongst viverrid rabies viruses, the opposite of our observation for canid viruses. The viverrid virus groups corresponded to geographical pockets that were independent of host species. Mokola viruses from Zimbabwe were shown to be different from those from South Africa and phylogenetic relationships of these viruses were related to their geographical location of origin. This study has demonstrated the value of multinational surveillance and investigation in understanding the epidemiology of lyssaviruses in southern Africa and elsewhere in Africa. The results presented here will serve as basis for future studies on lyssaviruses in Africa and will contribute to the improved surveillance and control programs of rabies and Mokola viruses in the region. / Thesis (PhD (Microbiology))--University of Pretoria, 2006. / Microbiology and Plant Pathology / unrestricted