Recombination at the emergence of the pathogenic rabbit haemorrhagic disease virus Lagovirus europaeus/GI.2

Abstract Rabbit haemorrhagic disease is a viral disease that emerged in the 1980s and causes high mortality and morbidity in the European rabbit ( Oryctolagus cuniculus ). In 2010, a new genotype of the rabbit haemorrhagic disease virus emerged and replaced the former circulating Lagovirus europaeus /GI.1 strains. Several recombination events have been reported for the new genotype Lagovirus europaeus /GI.2, with pathogenic (variants GI.1a and GI.1b) and benign (genotype GI.4) strains that served as donors for the non-structural part while GI.2 composed the structural part; another recombination event has also been described at the p16/p23 junction involving GI.4 strains. In this study, we analysed new complete coding sequences of four benign GI.3 strains and four GI.2 strains. Phylogenetic and recombination detection analyses revealed that the first GI.2 strains, considered as non-recombinant, resulted from a recombination event between GI.3 and GI.2, with GI.3 as the major donor for the non-structural part and GI.2 for the structural part. Our results indicate that recombination contributed to the emergence, persistence and dissemination of GI.2 as a pathogenic form and that all described GI.2 strains so far are the product of recombination. This highlights the need to study full-genomic sequences of lagoviruses to understand their emergence and evolution.