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

Joe Kgaladi,Louis H Nel,Wanda Markotter

doi:10.4102/ojvr.v80i1.511

Abstract

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.

Highlights

Rabies is a fatal disease of mammals, including humans, and is caused by viruses of the genus Lyssavirus in the family Rhabdoviridae, order Mononegavirales
The Lyssavirus genus consists of twelve classified species (ICTV Official Taxonomy: Updates since the 8th Report), of which five (Rabies virus [RABV], Lagos bat virus [LBV], Mokola virus [MOKV] and Duvenhage virus [DUVV]) have been isolated in Africa
Different strains of mice as well as different passages of the virus strains were used in determining the importance of these pathogenic domains. Mutations such as Arg 333 on the G protein were shown to be important in pathogenicity using different passages and different strains of mice (Coulon et al 1998; Dietzschold et al 1983; Seif et al 1985). These results demonstrated the importance of comparing a number of pathogenic domains when studying the pathogenicity of specific lyssavirus isolates

Summary

Introduction

Rabies is a fatal disease of mammals, including humans, and is caused by viruses of the genus Lyssavirus in the family Rhabdoviridae, order Mononegavirales. The Lyssavirus genus consists of twelve classified species (ICTV Official Taxonomy: Updates since the 8th Report), of which five (Rabies virus [RABV], Lagos bat virus [LBV], Mokola virus [MOKV] and Duvenhage virus [DUVV]) have been isolated in Africa. There are five different clusters of mongoose variant viruses in southern Africa (Nel et al 2005). The clusters are defined by the geographic regions in which the viruses were isolated. Isolates from more than one different mongoose species were found within a cluster. Cohen et al (2007) reported six different clusters of canid variant viruses in southern Africa. The clusters were defined by geographic location and included virus isolates from four provinces of South Africa. For MOKV several different phylogenetic groupings were observed based on geographical location (Sabeta et al 2010)

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