Identifying molecular virulence factors of rabbit haemorrhagic disease virus

Abstract

Rabbit haemorrhagic disease virus (RHDV) is a highly virulent pathogen classified within the genus Lagovirus, family Caliciviridae. Susceptible adult rabbits infected by RHDV die within 72 hours from acute hepatitis; however, it is still unknown which components of the virus account for this extraordinary virulence, mainly due to the lack of an effective cell culture system for this virus. It has been suggested that RHDV is one of the examples of an emerging disease where a previously non-pathogenic virus became a lethal pathogen by mutation and subsequently spread around the world. These sudden changes to extreme pathogenicity point to a “molecular switch”, an event that was triggered when a single or very few mutations caused an immediate and complete change of the virus’ behaviour in the host. Recently, a benign Rabbit calicivirus (strain RCV-A1), a non-pathogenic relative of RHDV, has been discovered in Australia. RCV-A1 does not cause any disease in rabbits. However, genome size and genome organisation of the nonpathogenic and the pathogenic viruses are similar and the amino acid sequences are approximately 85% identical. It means that now two complementary sets of closely related genes are available: one set from the extremely pathogenic RHDV and the other from the completely benign RCV-A1. Analysis of these two genomes and the encoded proteins can give insights into functional differences that may account for the different pathogenicity of the two viruses. This project aims to better understand RHDV replication mechanisms by characterising its non-structural proteins and comparing the genetic material of a pathogenic RHDV strain with that of a non-pathogenic, but closely related benign rabbit calicivirus.

Date of Award	2017
Original language	English
Supervisor	Michael FRESE (Supervisor) & Ian Ramshaw (Supervisor)