Molecular epidemiology of African mongoose rabies and Mokola virus

Abstract

The African continent sustains a variety of lyssaviruses and this study focused on two of these lyssaviruses that are unique to the continent namely rabies virus mongoose biotype and Mokola virus (MOKV). Rabies virus (RABV) belongs to genotype (gt) 1 of the Lyssavirus genus in the family Rhabdoviridae, order Mononegavirales, while Mokola virus belongs to gt3 of this genus. Both these viruses cause fatal rabies encephalitis in vertebrate animals. Genotype 1 (rabies virus) isolates from southern African countries display great genetic diversity and are grouped into two main biotypes i.e. canid and mongoose biotypes. Due to the difference in the epidemiology and pathogenesis of these biotypes, it has been hypothesized that the two biotypes were introduced into Africa at different times. The objective was to study the molecular phylogeny of representative rabies virus isolates of the mongoose biotype, isolated in South Africa and Zimbabwe over a period of 27 years, towards a better understanding of the origin of this group. In this study the complete nucleoprotein (1353 nucleotides) and glycoprotein (1575 nucleotides) genes were sequenced. The evolutionary dynamics of this virus variant was investigated using Bayesian methodology, allowing for rate variation among the different viral lineages. The phylogenetic analysis of this dataset confirms previous findings of extended evolutionary adaptation of isolates in specific geographic areas. Furthermore when these isolates are analyzed together with rabies virus isolates from across the world, they still form an independent cluster separate from any other African rabies virus isolates, thereby hinting towards a separate introduction to the continent before that of canid rabies. Molecular clock analysis estimates the age of the mongoose biotype to be approximately 200 years old, which is in concurrence with literature describing rabies in mongooses since the early 1800’s. In addition, a phylogenetic analysis of Mokola virus isolates (gt3) from South Africa, Zimbabwe, Cameroon and Central African Republic is described. All the South African isolates before 2008, as well as most of the Zimbabwean isolates (except isolate 21846) were included in this analysis. The complete nucleoprotein gene (1353nt) was amplified and sequenced. Phylogenetic analysis showed virus grouping to correspond to their geographic location. Further analysis showed Mokola virus isolates to display genetic diversity similar to that found in representative gt1 isolates. Copyright