Temporal dynamics and turnover of rabbit hemorrhagic disease virus 2 (RHDV2/GI.2) in wild lagomorphs from northeastern Spain

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Abstract

In Mediterranean ecosystems, emerging lagoviruses, particularly rabbit hemorrhagic disease virus 2 (RHDV2/GI.2), have caused substantial mortality in European rabbits ( Oryctolagus cuniculus ) and, sporadically, hares ( Lepus spp.). Recombination is common among RNA viruses, including lagoviruses, and shapes their evolution, influencing pathogenicity, epidemiology, and host range. However, the viral dynamics of recombinant strains in wild populations remain largely unknown. In this work, we analyse 66 RHDV2/GI.2 coding sequences from European rabbits (n = 44), European brown hares (n = 21) and one Iberian hare collected in Catalonia (NE Spain) between 2014–2024, to characterise temporal patterns and turnover of the different recombinant lineages. All strains shared the GI.2 capsid backbone but with four distinct non-structural genomic profiles: GI.3P–GI.2, GI.1bP–GI.2, GI.4(p16)–GI.1bP–GI.2, and GI.4P–GI.2. The four recombinants were detected in European brown hares, whereas rabbits were infected by only three, with the same recombinant present in areas where both species coexist. The Iberian hare was infected by a GI.4P-GI.2 recombinant, where rabbits showed the same lineage. Generalised additive models revealed significant interactions between recombinant type and year of detection, indicating contrasting turnover and temporal dynamics. Over the decade, GI.3P-GI.2 appeared transiently in 2014, GI.1bP-GI.2 strains dominated until 2019, and GI.4-related recombinants progressively replaced them, with GI.4P-GI.2 prevailing from 2020 onwards. Our findings reveal that recombinant strains have been successively replaced over time in leporid species from northeastern Iberia, likely due to the selective advantages provided by the non-structural genomic region, highlighting recombination as a major driver of viral dynamics.

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