The diversity of lagoviruses (Caliciviridae) in Australia has increased considerably in recent years. By the end of 2017, five variants from three viral genotypes were present in populations of Australian rabbits, while prior to 2014 only two variants were known. To understand the evolutionary interactions among these lagovirus variants, we monitored their geographical distribution and relative incidence over time in a continental-scale competition study. Within 3 years of the incursion of rabbit haemorrhagic disease virus 2 (RHDV2, denoted genotype GI.1bP-GI.2 [polymerase genotype]P-[capsid genotype]) into Australia, two novel recombinant lagovirus variants emerged: RHDV2-4e (genotype GI.4eP-GI.2) in New South Wales and RHDV2-4c (genotype GI.4cP-GI.2) in Victoria. Although both novel recombinants contain non-structural genes related to those from benign, rabbit-specific, enterotropic viruses, these variants were recovered from the livers of both rabbits and hares that had died acutely. This suggests that the determinants of host and tissue tropism for lagoviruses are associated with the structural genes, and that tropism is intricately connected with pathogenicity. Phylogenetic analyses demonstrated that the RHDV2-4c recombinant emerged independently on multiple occasions, with five distinct lineages observed. Both the new RHDV2-4e and -4c recombinant variants replaced the previous dominant parental RHDV2 (genotype GI.1bP-GI.2) in their respective geographical areas, despite sharing an identical or near-identical (i.e. single amino acid change) VP60 major capsid protein with the parental virus. This suggests that the observed replacement by these recombinants was not driven by antigenic variation in VP60, implicating the non-structural genes as key drivers of epidemiological fitness. Molecular clock estimates place the RHDV2-4e recombination event in early to mid-2015, while the five RHDV2-4c recombination events occurred from late 2015 through to early 2017. The emergence of at least six viable recombinant variants within a 2-year period highlights the high frequency of these events, detectable only through intensive surveillance, and demonstrates the importance of recombination in lagovirus evolution.

中文翻译：

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非结构基因和结构基因之间频繁的基因型间重组是杯状病毒流行病学适应性的主要驱动力

近年来，澳大利亚拉戈病毒（杯状病毒科）的多样性显着增加。到 2017 年底，来自三种病毒基因型的五个变体出现在澳大利亚兔群中，而在 2014 年之前，只有两个变体已知。为了了解这些 lagovirus 变体之间的进化相互作用，我们在一项大陆规模的竞争研究中监测了它们的地理分布和相对发病率。在兔出血性疾病病毒 2（RHDV2，表示基因型 GI.1bP-GI.2 [聚合酶基因型]P-[衣壳基因型]）入侵澳大利亚的 3 年内，出现了两种新型重组兔病毒变体：RHDV2-4e（基因型GI.4eP-GI.2) 在新南威尔士州和 RHDV2-4c (基因型 GI.4cP-GI.2) 在维多利亚州。尽管这两种新型重组体都包含与良性、兔特异性、嗜肠病毒相关的非结构基因，但这些变体是从急性死亡的兔子和野兔的肝脏中回收的。这表明，lagoviruses 的宿主和组织嗜性的决定因素与结构基因有关，并且嗜性与致病性密切相关。系统发育分析表明 RHDV2-4c 重组体多次独立出现，观察到五个不同的谱系。新的 RHDV2-4e 和 -4c 重组变体在各自的地理区域取代了以前的主要亲本 RHDV2（基因型 GI.1bP-GI.2），尽管共享相同或几乎相同（即单个氨基酸变化）的 VP60 主要衣壳蛋白与亲本病毒。这表明观察到的这些重组体的替代不是由 VP60 中的抗原变异驱动的，这表明非结构基因是流行病学适应性的关键驱动因素。分子钟估计将 RHDV2-4e 重组事件置于 2015 年初至年中，而 5 次 RHDV2-4c 重组事件发生在 2015 年底至 2017 年初。在 2 年内至少出现 6 个可行的重组变体突出显示这些事件的高频率，只有通过密集的监测才能检测到，并证明了重组在 lagovirus 进化中的重要性。