Academic literature on the topic 'Lyssavirus'

Rabies, the archetypal lyssavirus, is one of the most feared viruses known to man and globally, is the cause of more than 55,000 deaths per year. Alongside rabies virus, numerous related lyssaviruses exist that are also capable of causing fatal disease, clinically indistinguishable from rabies. Whilst the human burden of these non-rabies lyssaviruses remains unknown, fatalities have been reported. The lyssavirus glycoprotein is the sole target for virus neutralising antibodies and several amino acid epitopes have been linked to virus neutralisation. Lyssaviruses are genetically and antigenically categorised into phylogroups that indicate the level of protection afforded by current vaccines. It is generally accepted that an antibody response to the currently available rabies vaccines affords protection against all viruses that are categorised into phylogroup I. However, this antibody response does not protect against lyssavirus species within phylogroups II and III. Indeed, experimental data has shown that the antibody repertoire induced by rabies virus vaccines is unable to neutralise viruses in these phylogroups. In this study we have generated lentivirus pseudotypes representing all currently defined lyssaviruses as well as including chimeric lyssavirus glycoproteins that have had their antigenic sites swapped between phylogroup I and II viruses. Using the wildtype lyssavirus pseudotypes we have confirmed a strong level of intra-phylogroup neutralisation in addition to very limited inter-phylogroup neutralisation. The antigenic site swap constructs have shown an alteration in both glycoprotein functionality alongside altered neutralisation profiles using a variety of vaccine induced and divergent lyssavirus specific sera. Promising cross protective candidates have been cloned into a vaccine strain full length backbone and reverse genetics has enabled rescue of these viruses. The growth kinetics of recombinant viruses have been studied in vitro and an investigation into the pathogenicity and degree of vaccine induced protection against these viruses in vivo has been conducted.

Lyssaviruses are bullet shaped negative-sense RNA viruses that are all able to cause the fatal encephalitic disease known as rabies. The genus currently consists of 17 formally recognised viral species with one tentative species awaiting classification. The prototype virus for the Lyssavirus genus is the well-known rabies virus (RABV), while all other species in the genus are classified as rabies-related viruses. In South Africa specifically, RABV, Lagos bat virus (LBV), Duvenhage virus (DUVV), and Mokola virus (MOKV) are known to circulate, with RABV and DUVV associated with human fatalities. Active surveillance on rabies-related lyssaviruses in bats, specifically African insectivorous bat species, is either very sporadic or non-existing, providing an inaccurate overall representation of prevalence, diversity, and geographic distribution. Therefore, we conducted viral nucleic acid surveillance for lyssaviruses in different insectivorous bat species in South Africa. These samples were collected during routine field surveillance and included bats that were found dead, appeared to be displaying abnormal behavior or taken as vouchers specimens as part of bat taxonomic studies. A quantitative real-time reverse transcription polymerase chain reaction assay, capable of detecting the diversity of lyssaviruses were used to test extracted RNA. Three brain samples tested positive and were further characterized by conventional RT-PCR, DNA sequencing and phylogenetic analyses targeting the nucleoprotein gene. One of the positive brains was detected from a Common slit-faced bat (Nycteris thebaica) and the other two positive brains were detected from the Natal long-fingered bat (Miniopterus natalensis). Phylogenetic analysis of the nucleoprotein indicated one detection to be a Duvenhage lyssavirus with the other two detections showing a close relationship with the West Caucasian bat virus species, previously only detected in Eastern Europe. However, a more than 20 % nucleotide divergence indicated it to be a potentially new lyssavirus species, Matlo bat lyssavirus. The virus was successfully isolated using the mouse inoculation test followed by full genome next generation amplicon sequencing. The results of the full genome characterisation further supported the initial findings with concatenated coding regions nucleotide divergence ranging between 16% and 23.7% as well as consistent phylogenetic tree topology groupings identical to initial phylogenetic analyses using multiple evolutionary models. The identification of a putative new lyssavirus highlights the importance of routine lyssavirus surveillance to understand the diversity. Further investigation is required to determine the possible reservoir species since the Natal long-fingered bats are known to co-roost with different bat species in caves. The potential of spillover to humans and other animals is unknown but people often enter these bat roosts for traditional and recreational purposes and bats do come into contact with several animal species including humans during foraging.<br>Dissertation (MSc)--University of Pretoria, 2021.<br>CDC- 5 NU2GGH001874-02-00 NRF-78566<br>Medical Virology<br>MSc<br>Restricted

Le sequencage du genome du virus mokola precise l'organisation genetique du genre lyssavirus qui presente de nombreux points communs avec les autres rhabdovirus de mammiferes. Des amorces oligonucleotidiques choisies dans des zones tres conservees du gene n se revelent efficaces pour le diagnostic par la reaction d'amplification en chaine par polymerase (pcr). Elles ont permis aussi l'etude du gene de la nucleoproteine de l'ensemble des prototypes de lyssavirus. Il en ressort un classement genotypique coherent avec le classement serologique anterieur. Cependant ces travaux renouvellent la taxinomie du genre lyssavirus par la creation de deux nouveaux genotypes 5 et 6 pour les virus des chauves-souris europeennes (ebl1 et 2) et confirment que les souches vaccinales ne tiennent aucun compte de la variabilite intrinseque chez les lyssavirus. Un baculovirus recombinant exprimant la glycoproteine du virus mokola a ete construit. La glycoproteine recombinante, de structure analogue a la proteine virale native, est protectrice chez la souris adulte. Enfin, l'analyse phylogenetique de virus de genotype 1 a ete entreprise sur la base de la sequence nucleotidique du gene n. Elle montre une correlation parfaite avec la provenance geographique des isolats, et permet de proposer que les isolats europeens de rage vulpine derivent de la rage du chien et du loup qui sevissait en europe au debut du siecle. Certains acides amines de la nucleoproteine et de la glycoproteine semblent critiques dans la specificite d'hote