Molecular epidemiology and pathogenesis of Lagos bat virus, a rabies-related virus specific to Africa

Lagos bat virus (LBV) belongs to genotype (gt) 2 of the lyssavirus genus in the family Rhabdoviridae, order Mononegavirales. This virus causes fatal rabies encephalitis in vertebrate animals and has only been reported from the African continent except for an imported case from African origin identified in France. The prototype lyssavirus is in fact rabies virus (gt 1) for which a variety of different vaccines are commercially available. These vaccines, however, do not provide protection against the gt 2 viruses. Genotype 2 viruses have not been well studied to date and the true risk for humans and animals is uncertain. The aim of this study was to investigate the epidemiology and pathogenicity of this uniquely African virus. In this project, our surveillance in South Africa reported six new LBV cases after this virus was not reported for the previous 12 years prior to this study. These results indicated that the incidence of this virus is greatly underestimated due to lack or absence of surveillance or ineffective diagnostic abilities of laboratories in Africa. Molecular epidemiological analysis of previously identified and new gt 2 isolates from this study indicated a high intragenotypic nucleotide and amino acid sequence diversity with respect to the Nucleo-, Phospho-, Matrix- and Glycoprotein genes. Based on these analyses, it has been proposed that two virus isolates that were previously reported as gt 2 LBV, may in fact constitute a new lyssavirus genotype. These findings emphasize the need to investigate different criteria for lyssavirus classification. As more lyssaviruses are discovered and with rapid progress in full genome sequencing, diversity becomes accentuated and challenges the criteria upon which lyssavirus taxonomy is based. As a compliment to these genetic findings, our study of viral pathogenicity in a murine model, identified that the pathogenicity of phylogroup II viruses has previously been underestimated. LBV poses a potential risk to humans and animals and future vaccine strategies should ideally include protection against phylogroup II viruses.Thesis (PhD)--University of Pretoria, 2011.Microbiology and Plant Pathologyunrestricte

Comparison of pathogenic domains of rabies and African rabies-related lyssaviruses and pathogenicity observed in mice

Several lyssavirus species occur in Africa (Rabies virus, Lagos bat virus, Mokola virus, Duvenhage virus, Shimoni bat virus and Ikoma lyssavirus), displaying a high sequence diversity between isolates belonging to the same species. There is limited information about comparative pathogenesis of these African lyssaviruses and this precludes authoritative opinion on the potential public and veterinary health impact. In this study, an analysis of representative African lyssaviruses attempted to correlate viral genomic sequence similarities and differences with the corresponding pathogenic profiles observed in mice. The study demonstrated that the virus isolates evaluated could be lethal to mice when introduced intramuscularly and that different isolates of the same lyssavirus species differ in their virulence. Using real-time polymerase chain reaction (PCR), viral RNA was detected in brain tissue, but no viral RNA was detected in the salivary glands or blood of mice that succumbed to infection. Comparison of known pathogenic domains indicated that pathogenicity is likely to be dependent on multiple domains. Cumulatively, our results re-emphasised the realisation that the pathogenicity of a lyssavirus species cannot be deduced based on studies of only a single isolate of the species or a single pathogenic domain.Scan this QR code with your smart phone or mobile device to read online.W.M. (University of Pretoria) was the project leader, L.H.N. (University of Pretoria) the project co-leader and J.K. (University of Pretoria) performed the experiments. All authors contributed to writing the manuscript.We thank the National Research Foundation, the International Society for Infectious Diseases, the International Foundation for Science and the Poliomyelitis Research Foundation for financial support.http://www.ojvr.orgam201

Assessing age related cranial characteristics and morphometrics of the Egyptian rousette (Rousettus aegyptiacus) from central Africa

This study assessed and related quantitative age determination methods based on cranial bone fusion and dental development to linear morphometrics in Rousettus aegyptiacus. Five growth development stages were identified based on cranial suture fusion and degree of second molar tooth eruption. Expressing these growth development stages in measurement size showed a linear growth pattern, with little overlap between smaller (stages 1, 2, and 3) and larger (stages 4 and 5) individuals. Total skull length (TSL), mastoid breadth (MB) and forearm length (FAL) had the highest influence on variation along the first and second principal components, accounting for 93% of variation. Advanced size was confirmed to relate to aging owing to development of cranial suture fusions and dental development. The smallest and largest individuals were significantly (P < 0.05) separated by measurements of TSL, MB and FAL. Meanwhile, some intermediate sized individuals overlapped despite being in different stages of cranial suture development. Species specific reliability in morphological approaches to age determination can be achieved by establishing a baseline reference, which may be directly related to the quantitative cementum growth assessment method.The National Research Foundation, Ditsong National Museum of Natural History small mammals collection and the Defence Threat Reduction Agency and the National United Nations Children’ Fund (UNICEF).https://bioone.org/journals/acta-chiropterologicaMedical VirologyZoology and Entomolog

Comparison of pathogenic domains of rabies and African rabies-related lyssaviruses and pathogenicity observed in mice

Several lyssavirus species occur in Africa (Rabies virus, Lagos bat virus, Mokola virus, Duvenhage virus, Shimoni bat virus and Ikoma lyssavirus), displaying a high sequence diversity between isolates belonging to the same species. There is limited information about comparative pathogenesis of these African lyssaviruses and this precludes authoritative opinion on the potential public and veterinary health impact. In this study, an analysis of representative African lyssaviruses attempted to correlate viral genomic sequence similarities and differences with the corresponding pathogenic profiles observed in mice. The study demonstrated that the virus isolates evaluated could be lethal to mice when introduced intramuscularly and that different isolates of the same lyssavirus species differ in their virulence. Using real-time polymerase chain reaction (PCR), viral RNA was detected in brain tissue, but no viral RNA was detected in the salivary glands or blood of mice that succumbed to infection. Comparison of known pathogenic domains indicated that pathogenicity is likely to be dependent on multiple domains. Cumulatively, our results re-emphasised the realisation that the pathogenicity of a lyssavirus species cannot be deduced based on studies of only a single isolate of the species or a single pathogenic domain.Scan this QR code with your smart phone or mobile device to read online.W.M. (University of Pretoria) was the project leader, L.H.N. (University of Pretoria) the project co-leader and J.K. (University of Pretoria) performed the experiments. All authors contributed to writing the manuscript.We thank the National Research Foundation, the International Society for Infectious Diseases, the International Foundation for Science and the Poliomyelitis Research Foundation for financial support.http://www.ojvr.orgam201

Molecular phylogeny of Duvenhage virus

The Duvenhage virus (DUVV) constitutes one of the 11 species in the Lyssavirus genus and causes fatal rabies encephalitis. The virus is associated with insectivorous bat species and three human cases have been reported, all of which were linked to contact with bats. Few of these isolates have been studied and thus little is known about the phylogeny and epidemiology of this lyssavirus. Until 2007, when an isolate was made from the East African country of Kenya, all isolations of this virus had been from southern Africa. This discovery led to many questions regarding the spread and diversity of this lyssavirus. Phylogenetic analysis indicated that the DUVV isolates constitute two different lineages, in which the southern African isolates group together to form one lineage and the more recent isolate from Kenya constitutes a new, second lineage. We found that the new isolate has a genetic variation that has not yet been seen for DUVV. Not only is our lack of knowledge regarding the geographical distribution of this uniquely African virus emphasised, but we have also demonstrated the potential diversity within this genotype.http://www.sajs.co.z

Mokola Virus in Domestic Mammals, South Africa

We recently identified 2 Mokola viruses from domestic mammals (a dog and a cat) in South Africa. These cases occurred 8 years after the last reported case of infection with this virus. Our findings emphasize the endemicity of rabies-related lyssaviruses in South Africa and the need to better understand the epidemiology of Mokola viruses

Leptospira and bats : story of an emerging friendship

A growing number of recent studies have highlighted bats as a reservoir for Leptospira bacteria, pointing out the potential role of bats in the epidemiology of the most widespread zoonotic disease in the world [1]. Because leptospirosis is a largely neglected disease, a number of unanswered questions remain about the ecology and evolution of Leptospira, especially those associated with bats. Here we summarize what has been recently learned about this emerging but enigmatic host–pathogen association. We show how this system can provide exciting new opportunities to obtain insights into the evolutionary ecology of bat-borne pathogens and propose future directions to disentangle the role of bats in human leptospirosis.The National Research Foundation, South Africa (NRF – N00595) to MD.http://www.plospathogens.orgam2016Microbiology and Plant Patholog

Lagos bat virus, an under-reported rabies-related lyssavirus

Lagos bat virus (LBV), one of the 17 accepted viral species of the Lyssavirus genus, was the first rabies-related virus described in 1956. This virus is endemic to the African continent and is rarely encountered. There are currently four lineages, although the observed genetic diversity exceeds existing lyssavirus species demarcation criteria. Several exposures to rabid bats infected with LBV have been reported; however, no known human cases have been reported to date. This review provides the history of LBV and summarizes previous knowledge as well as new detections. Genetic diversity, pathogenesis and prevention are re-evaluated and discussed.This research is supported in part by the South African Research Chair Initiative (held by Wanda Markotter) of the Department of Science and Innovation and administered by the National Research Foundation of South Africa (UID: 98339). The National Research Foundation funded the equipment based at the DNA Sanger sequencing facility in the Faculty of Natural and Agricultural Sciences, University of Pretoria (UID: 78566).https://www.mdpi.com/journal/virusesdm2022Medical Virolog

Reverse transcription recombinase polymerase amplification assay for rapid detection of canine associated rabies virus in Africa

Rabies is a neglected disease mostly affecting the developing world. Accurate and reliable diagnostic and surveillance data forms the foundation for the formulation and monitoring of control strategies. Although various sensitive and specific tests are available for detection of rabies virus, implementation of these tests in low-resource settings are challenging and remains limited. In this study, we describe the developed of a reverse transcription recombinase polymerase amplification assay for the detection of rabies virus. The analytical sensitivity of this assay was determined to be 562 RNA copies and was performed in 20 minutes. The diagnostic sensitivity of the RT-RPA was 100% for detection of rabies virus in field samples. In conclusion, the RT-RPA assay allowed for very quick and sensitive detection of rabies virus and could be adapted for use in low-source settings.Supporting information: S1 Table. Details of rabies virus sequences used for primer and probe design for the RT-RPA assay.S2 Table. Evaluation of the mismatches between the RT-RPA primer and probe set binding regions to rabies-related lyssaviruses.The South African Research Chair initiative of the Department of Science and Technology and National Research Foundation of South Africa and the Poliomyelitis Research Foundation.http://www.plosone.orgpm2020BiochemistryGeneticsMedical VirologyMicrobiology and Plant Patholog

The excreted microbiota of bats : evidence of niche specialisation based on multiple body habitats

Animal-associated microbiotas form complex communities, which play crucial functions for their host, including susceptibility to infections. Despite increasing attention to bats as reservoirs of zoonotic pathogens, their microbiota is poorly documented, especially for samples potentially implicated in pathogen transmission such as urine and saliva. Here, using low-biomass individual samples, we examined the composition and structure of bacterial communities excreted by insectivorous bats, focusing on three body habitats (saliva, urine and faeces). We show that niche specialisation occurs as bacterial community composition was distinct across body habitats with the majority of phylotypes being body habitat specific. Our results suggest that urine harbours more diverse bacterial communities than saliva and faeces and reveal potentially zoonotic bacteria such as Leptospira, Rickettsia, Bartonella and Coxiella in all body habitats. Our study emphasised that, in addition to the traditional use of gut-associated samples such as faeces, both urine and saliva are also of interest because of their diverse microbiota and the potential transmission of pathogenic bacteria. Our results represent a critical baseline for future studies investigating the interactions between microbiota and infection dynamics in bats.This work was supported by the National Research Foundation (NRF) of South Africa [Grant UID 78566 (NRF RISP grant for the ABI3500), UID 91496 and UID 92524], and by the Grant or Cooperative Agreement Number, [1U2GGH001874-01], funded by the Centers for Disease Control and Prevention. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Centers for Disease Control and Preventionor the Department of Health and Human Services. MD’s postdoctoral fellowship is funded by a Capacity Building Grant from the National Research Foundation, South Africa [Grant UID 92524].http://femsec.oxfordjournals.org2018-01-31hb2017Centre for Wildlife ManagementMedical Virolog