Abstract

Rabies is a fatal zoonotic infection of the central nervous system of mammals and has been known to humans for millennia. The etiological agent, is a neurotropic RNA virus in the order Mononegavirales, family Rhabdoviridae, genus Lyssavirus. There are currently accepted to be two cycles for rabies transmission: the urban cycle and the sylvatic cycle. The fact that both cycles originated from a common RABV or lyssavirus ancestor and the adaptive divergence that occurred since then as this ancestor virus adapted to a wide range of fitness landscapes represented by reservoir species in the orders Carnivora and Chiroptera led to the emergence of the diverse RABV lineages currently found in the sylvatic and urban cycles. Here we study full genome phylogenies and the time to the most recent common ancestor (TMRCA) of the RABVs in the sylvatic and urban cycles. Results show that there were differences between the nucleotide substitution rates per site per year for the same RABV genes maintained independently in the urban and sylvatic cycles. The results identify the most suitable gene for phylogenetic analysis, heterotachy among RABV genes and the TMRCA for the two cycles.

Highlights

  • Rabies is endemic throughout the world apart from the Antarctic, Australia, Japan and New Zealand

  • If only one amplification step is carried out to obtain the whole RABV genome sequence, the resulting sequence is more reliable as the use of different amplicons can, even if these are from the same viral sample, generate amplicons of different viral subpopulations for each of the segments being studied (Drummond et al, 2006b; Lauring et al, 2012)

  • In this study we investigated 25 of the 35 lineages already described for the bat-related RABV in the Americas (Favoretto et al, 2001; Drummond et al, 2006b; Oliveira et al, 2010; Streicker et al, 2010; Almeida et al, 2011; Kuzmin et al, 2012; Lauring et al, 2012), of which three (LC, LB and LS) grouped into a single monophyletic cluster

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Summary

Introduction

Rabies is endemic throughout the world apart from the Antarctic, Australia, Japan and New Zealand. RABV is one of seventeen members of the genus Lyssavirus (King, A.M.K; Adans, M.J; Carstens, E.B; Lefkowitz 2012), fifteen of which have members of Chiroptera as exclusive reservoirs, showing the importance of this order as a reservoir for the genus (Rupprecht et al, 2017; Hu et al, 2018) This lends support to the hypothesis that various existing RABV lineages had an RABV specific to bats as a common ancestor (Badrane and Tordo, 2001; Hayman et al, 2016; Velasco-Villa et al, 2017) and that this ancestral lineage differentiated into the various lineages in the urban and sylvatic cycles (Oliveira et al, 2010; Streicker et al, 2010, 2012a,b; Kuzmin et al, 2012). There are known to be two rabies transmission cycles: the urban cycle, in which the dog is the main reservoir and transmits the virus to other dogs, other domestic animals and man; and the sylvatic cycle, which is maintained by different terrestrial mammals and chiropterans (Acha and Szyfres, 2003)

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