Recombination between non-structural and structural genes as a mechanism of selection in lagoviruses: The evolutionary dead-end of an RHDV2 isolated from European hare

Comment on Shah et al. Genetic Characteristics and Phylogeographic Dynamics of Lagoviruses, 1988–2021. Viruses 2023, 15, 815

“…Nonetheless, hare species seem to remain as dead-end hosts, and rabbits appear to have a higher susceptibility to lethal disease than other leporids, notwithstanding the limited availability of comparative studies [38]. Phylogenetic analysis in countless previous publications from different labs globally clearly confirm the separation between "rabbit lagoviruses" and "hare lagoviruses", e.g., [2,7,13,30,33,39]. Furthermore, this partition is confirmed by genetic distances between sequences from these groups (Figure 1).…”

“…In their work, Shah and colleagues identified six recombination events: one in VP60, one in the non-structural protein RNA-dependent RNA polymerase (RdRp), and four near the boundary between RdRp and the capsid protein [1], the latter four being consistent with the hotspot of recombination previously described [3,7,10,13]. Despite acknowledging the existence of recombination in the dataset and having included additional VP60-and VP10based phylogenies, their main conclusions were still inferred from the full-length phylogeny, which led to erroneous conclusions.…”

“…This reshuffling of viral genomes results in a mix of genes with different evolutionary histories, and the new genomic combinations might confer novel features to the resulting virus, such as higher pathogenic potential, evasion from the host immune system, resistance to antiviral therapies and vaccines, the expansion of host range (species jump), or the modification of cell or host tropism. As in other RNA viruses, recombination has been described for lagoviruses, with a major recombination hotspot located at the boundary between the non-structural and structural gene-encoding regions and other not-so-frequent breakpoints scattered throughout the genome e.g., [ 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. Notably, recombination seems to have contributed to the emergence of GI.2 in 2010 by combining the non-structural proteins of a non-pathogenic GI.3 [ 2 ] with the structural proteins of a novel virus, GI.2 [ 14 ].…”

“…This novel virus was also shown to have recombined with pathogenic GI.1a and GI.1b, as well as non-pathogenic GI.4 [ 10 , 15 ], all contributing to the pool of circulating lagoviruses. Hares have also been a source of new viruses, with both pathogenic and non-pathogenic GII recombining with GI.2 [ 7 , 13 ]. Nonetheless, recombination is not restricted to this genotype, and other key examples of the importance of this mechanism in lagoviruses include the combination of non-pathogenic with classical pathogenic strains, such as the GI.4eP-GI.1a and the GI.3P-GI.1d [ 12 , 16 ] that were able to spread and cause outbreaks in Australia and Europe, respectively.…”

Identification and Characterisation of a Myxoma Virus Detected in the Italian Hare (Lepus corsicanus)

“…Carbon-coated grids were floated on a drop of the viral suspension for 10 min. The second method was performed according to that previously reported [ 15 ]. Samples were frozen and thawed twice and centrifuged at 4000× g for 20 min and 9300× g for 10 min to clarify the supernatant.…”