Faculty of Natural and Agricultural Sciences
School of Biological Sciences
Department of Microbiology and Plant Pathology
Evolution of Rhabdoviruses and epidemiology of lyssaviruses
The origin and evolution of viruses are of as much interest in the discipline of virology as is the evolution of life forms to paleontology, and is also important in understanding future evolvement of new virus strains. The genetic evolution of the lyssaviruses within the Rhabdoviridae family has become one of our main interests. Elucidating the epidemiology and evolutionary history of two indigenous viral lineages, viz. Mokola virus and the mongoose rabies virus, are core objectives of this research interest. Within the Mononegavirales, the Rhabdoviridae is a family of which the members cumulatively infect more than 200 species, which include a broad variety of plants, insects, fish, birds and mammals. Among the lyssaviruses (one several genera) it is of particular interest that Mokola virus has been found in insectivorous shrews and the virus is known to be able to replicate in insects and insect cells – it is also the only lyssavirus for which a reservoir species is not known and, bizarrely, it has never been isolated from bats. All the other lyssaviruses can either be transmitted by insectivorous bats or are exclusive to insectivorous bats. This last category also includes the putative Asian genotypes i.e. Aravan, West Caucasian bat virus, Khujand and Irkut viruses. Three other rhabdoviruses were once considered as putative lyssaviruses, and have been encountered in insects only, viz. Rochambeau, Obodhiang and Kotonkan. It is therefore tempting to speculate that bat lyssaviruses emerged from an insect rhabdovirus and that one of these emerged as the now global classical dog rabies virus. Dog rabies emerged only in recent decades over much of the world, including Africa and continues to radiate in new host species.
(1) Recently, an excellent plant virology programme has joined our laboratory. Jointly, ours is one of few virology laboratories in which animal and plant viruses are studied in parallel. On this opportune interface, it is our intention to carry out a more comprehensive molecular evolution study of the rhabdoviruses of animals, insects and plants. A number of new and unindentified nucleo- and cyto-rhabdoviruses from South Africa will be studied, together with insect rhabdoviruses of African origin and animal viruses such as Mokola and rabies viruses. These studies will involve the generation of molecular epidemiological clocks and other bioinformatical information, but also investigate physical and biological properties of viruses such as the relative ability to grow on various types of animal and insect cells.
(2) There has never been any comprehensive epidemiological study of Lagos Bat virus or Mokola virus and these viruses remain among the most obscure in the Lyssavirus genus. However, these lyssaviruses have been encountered everywhere on the continent, where it was competently looked for and we have described various recent isolations of Mokola and LBV from South Africa. Most recently we regularly isolated LBV from bats, but also isolated LBV for the first time from terrestrial wildlife and implicated LBV in rabies vaccine failures of dogs. These findings re-emphasized our lack of understanding of the pathogenicity or epidemiology of lyssaviruses throughout Africa and renewed the interest in the rabies-related viruses in particular. Internationally, these aspects are closely linked to similar questions of other lyssaviruses – including the newly discovered viruses from Asia as well as the better known genotypes like the European and Australian bat lyssaviruses. As one of our contributions towards a better understanding of the genetic diversity, geographic origin and pathogenesis of the phylogroup II viruses we have initiated a molecular epidemiological analyses of all the LBV isolates and all the Mokola virus isolates, both those newly isolated here and those available from local and international archives. It has already become evident that errors have been made in the classification of various isolates and we hope to contribute to a better understanding of the epidemiology of the African lyssaviruses. Apart from the quest for vaccines that will protect against the non-rabies lyssaviruses, the most fundamental questions regarding Lagos Bat virus and Mokola virus and their similarities or differences with rabies virus remains: (1) the identification of the reservoir of Mokola virus and whether or not this virus can infect bats (as all the other lyssaviruses do); (2) whether or not Lagos Bat virus could be regarded as a potential threat to human health (as all the other lyssaviruses are). In searching for answers, we have initiated a comprehensive analyses and comparison of pathogenicity of these viruses in appropriate animal models.
(3) Following our characterization of the southern African mongoose rabies virus, the origin of this apparently unique variant of rabies virus in southern Africa has become even more intriguing and there seems to be at least two possible explanations, which our future research will explore and seek to clarify - briefly: (1) A separate introduction from bats to small herpestid carnivores of southern Africa, sometime after the original establishment of cosmopolitan dog rabies and North American raccoon rabies (phylogenetically, the mongoose variant seems to be closer to the cosmopolitan variant than to the raccoon variant). Presumably, this would mean that a bat variant of rabies virus, with ancestral links to the European progenitor, would have to have been present in southern Africa a few centuries ago. If this is the case, the bat virus itself must have become extinct in southern Africa, since there is no evidence of rabies in bats in southern Africa, or anywhere on the African continent. Assuming that there are no extant true rabies viruses in African or other Old World bats, it has to be considered unlikely that a well established bat rabies virus would have become extinct in a stable reservoir(s) during the recent past. (2) Introduction of terrestrial mongoose rabies into southern Africa at some time before the dissemination of the cosmopolitan variant. However, given the efficiency with which dog rabies has manifested in dogs and a huge variety of wildlife during the past 50 years, the mongoose virus is unlikely to ever have been a dog virus, given the specificity and adaptation of this virus for species of the Herpestidae and its tendency to cause dead-end infections in other hosts, including canids. If this is the case, it would constitute a very different scenario from rabies in mongooses in the Caribbean. These mongooses were imported into the Caribbean from India in the 1870’s and 1880’s and genetic analysis indicate that these mongooses acquired cosmopolitan dog rabies from endemically infected Caribbean dogs, resulting in a first major mongoose rabies outbreak in 1950. Globally, the epizootiology of rabies in mongooses is poorly understood, outside of southern Africa and the secondary foci in the Caribbean.
(4) As an established rabies epidemiology facility in southern Africa, we continue to be involved with research activities related to the radiation of rabies into and through the animals of our region. In our investigations of the canid rabies virus of southern Africa, we have recently focused on the molecular epidemiology of the ongoing dog rabies epidemic in Kwazulu/Natal. For the first time we have obtained a picture of the viruses involved and their movement within and among the municipal areas of this province. Our research indicated that, contrary to traditional belief, there may have been multiple introductions of rabies virus into the province, with implication for the future control of rabies in this province and elsewhere in southern Africa. One of these introductions may have been from a virus cycle associated with jackal and dog cycles. Whereas the importance of dogs as rabies hosts throughout Africa is without question, the role of jackals as important hosts is controversial. With regard to the transmission of rabies, it is only in southern Africa that jackals are considered to be important hosts of the virus. Some studies have indicated that they are able to support rabies cycles independently of dogs, while others contradict this finding. It is clear that the mechanisms involved in sustaining rabies in African canids are not yet understood. As our contribution, we are expanding our molecular epidemiological data from Kwazulu/Natal in 3 directions: (1) by inclusion of virus cycles towards the north, including Mpumalanga and Northern Province (2) by inclusion of viruses from neighbouring countries, Lesotho, Swaziland and Mozambique and (3) by inclusion of virus cycles associated with the Eastern Cape Province (where the first documented outbreak of rabies in South Africa occurred in 1893). (4) In other regions, the bat eared fox emerged as maintenance host for canid rabies. In this case, we were able to demonstrate the autonomy of these cycles and the independent evolution of the viruses involved.