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GENERAL INTRODUCTION
The nature of viruses only began to be understood just over one hundred years ago, despite the fact that their concept as a natural phenomenon separate from all other organisms had been realised much earlier before the turn of the 19th century. There is evidence in ancient Chinese literature and Egyptian art for what may have been smallpox and other viral infections such as poliomyelitis and measles (Levy et al., 1994).
The early successes in the study of microorganisms were not based on any real understanding of the nature of the infectious agents or pathogens but on the diseases that they caused. Antony Van Leeuwenhoek identified bacteria with the aid of a microscope and referred to them as small animals or « animalscules » (Myrvik and Weiser, 1988; Prescot et al., 1996). The significance of the « animalscules » identified by Antony van Leeuwenhoek only became apparent when Robert Koch and Louis Pasteur pronounced their « germ theory ». At the time, Pasteur worked on rabies, but was unable to discriminate between bacteria and other infectious agents of disease, such as bacterial toxins.
At the turn of the 19th century, viruses were recognised as agents responsible for diseases of plants (tobacco mosaic) and animals (foot and mouth) through initial experimentation by Dimitri Iwanowski and Martinus Beijerinick (see historical reviews by Bos, 1999 and Lecoq 2001). Through these studies, viruses were shown to be submicroscopic and obligate intracellular parasites. In fact, it is possible that viruses could have been in co-existence with living organisms since the origin of life (Levy et al., 1994). While many viruses are harmful to their host, others are symbiotic and may give an advantage to the infected host. For example, viruses could provide a gene that mediates a needed metabolic capability or drug resistance. Mammalian evolution would in fact not have been possible without viruses. Placental morphogenesis results from the syncytium-forming properties of syncytin, a gene that was borrowed from an endogenous retrovirus (Mi et al., 2000). Several viruses have however raised great concern in the past century because of serious threats in humans; influenza (1918, 1957, 1968, 1977) (Alexander and Brown, 2000), poliomyelitis (1930s), herpes (l960s), acquired immunodeficiency syndrome (HIV) (l980s) and Ebola and Marburg in the 1990s (Le Guenno, 1997; Brown, 1997; Levy et al., 1994). The diseases caused by these viruses have brought increased attention to the field of virology.
CHAPTER ONE INTRODUCTION AND LITERATURE REVIEW
1.1 General introduction
1.2 Rabies: a short history.
1.3 The Rhabdoviridae family
1.4 Vesiculovirus genus
1.5 Lyssavirus genus
1.6 Rabies virus genome organisation and replication
1.7 RNA quasi-species
2 Rabies pathogenesis
3 Global rabies situation.
3.1 Europe and Asia
3.2 The Americas
3.3. Rabies in Africa.
4 Rabies control
5 Methods used in the study
5.1 Polymerase chain reaction
5.2 Nucleic acid sequencing
5.3 Phylogenetic methods
5.4 Resampling methods: Bootstrapping
6 Aims 0f the study.
CHAPTER TWO MOLECULAR EPIDEMIOLOGY OF CANINE RABIES IN ZIMBABWE AND SOUTH AFRICA.
2.1 Summary
2.2 Introduction.
2.3 Materials and methods
2.4 Results
2.5 Discussion
CHAPTER THREE MOLECULAR EPIDEMIOLOGY OF VIVERRID RABIES IN ZIMBABWE AND SOUTH AFRICA.
3.1 Summary
3.2 Introduction.
3.3 Materials and methods.
3.4 Results
3.5 Phylogenetic analyses.
3.6 Discussion
CHAPTER FOUR GENOTYPIC ANALYSES OF MOKOLA VIRUSES FROM ZIMBABWE AND SOUTH AFRICA.
4.1 Summary
4.2 Introduction
4.3 Materials and methods.
4.4 Results..
4.5 Discussion
CONCLUDING REMARKS
APPENDIX 1Multiple alignment of nucleotide sequences of southern African canid
viruses
Appendix 3: Multiple alignment of viverid rabies viruses from Zimbabwe and South
Africa
Appendixes 4a-4d: Genetic distances of viverrid rabies viruses from Zimbabwe and
South Africa.
Appendix S: Multiple alignment of nucleic acid sequences of Mokola viruses from
Zimbabwe and South Africa.
Appendix 6: Genetic distances of Mokola virus nucleic acid sequences from
Zimbabwe and South Africa
