关键词: Animal experiments Lagovirus RHDV2 Recombination Virus selection

Mesh : Animals Rabbits Hares Phylogeny Caliciviridae Infections / veterinary epidemiology Biological Evolution Hemorrhagic Disease Virus, Rabbit / genetics Recombination, Genetic

来  源:   DOI:10.1016/j.virusres.2023.199257   PDF(Pubmed)

Abstract:
The genus Lagovirus, belonging to the family Caliciviridae, emerged around the 1980s. It includes highly pathogenic species, rabbit hemorrhagic disease virus (RHDV/GI.1) and European brown hare syndrome virus (EBHSV/GII.1), which cause fatal hepatitis, and nonpathogenic viruses with enteric tropism, rabbit calicivirus (RCV/GI.3,4) and hare calicivirus (HaCV/GII.2). Lagoviruses have evolved along two independent genetic lineages: GI (RHDV and RCV) in rabbits and GII (EBHSV and HaCV) in hares. To be emphasized is that genomes of lagoviruses, like other caliciviruses, are highly conserved at RdRp-VP60 junctions, favoring intergenotypic recombination events at this point. The recombination between an RCV (genotype GI.3), donor of non-structural (NS) genes, and an unknown virus, donor of structural (S) genes, likely led to the emergence of a new lagovirus in the European rabbit, called RHDV type 2 (GI.2), identified in Europe in 2010. New RHDV2 intergenotypic recombinants isolated in rabbits in Europe and Australia originated from similar events between RHDV2 (GI.2) and RHDV (GI.1) or RCV (GI.3,4). RHDV2 (GI.2) rapidly spread worldwide, replacing RHDV and showing several lagomorph species as secondary hosts. The recombination events in RHDV2 viruses have led to a number of viruses with very different combinations of NS and S genes. Recombinant RHDV2 with NS genes from hare lineage (GII) was recently identified in the European hare. This study investigated the first RHDV2 (GI.2) identified in Italy in European hare (RHDV2_Bg12), demonstrating that it was a new virus that originated from the recombination between RHDV2, as an S-gene donor and a hare lagovirus, not yet identified but presumably nonpathogenic, as an NS gene donor. When rabbits were inoculated with RHDV2_Bg12, neither deaths nor seroconversions were recorded, demonstrating that RHDV2_Bg12 cannot infect the rabbit. Furthermore, despite intensive and continuous field surveillance, RHDV2_Bg12 has never again been identified in either hares or rabbits in Italy or elsewhere. This result showed that the host specificity of lagoviruses can depend not only on S genes, as expected until today, but potentially also on some species-specific NS gene sequences. Therefore, because RHDV2 (GI.2) infects several lagomorphs, which in turn probably harbor several specific nonpathogenic lagoviruses, the possibility of new speciation, especially in those other than rabbits, is real. RHDV2 Bg_12 demonstrated this, although the attempt apparently failed.
摘要:
Lagovirus属,属于杯状病毒科,大约在1980年代出现。它包括高致病性物种,兔出血性疾病病毒(RHDV/GI.1)和欧洲褐兔综合征病毒(EBHSV/GII.1),导致致命的肝炎,和具有肠道嗜性的非致病性病毒,兔杯状病毒(RCV/GI.3,4)和兔杯状病毒(HaCV/GII.2)。拉戈病毒已经沿着两个独立的遗传谱系进化:兔的GI(RHDV和RCV)和兔的GII(EBHSV和HaCV)。需要强调的是,泻湖病毒的基因组,像其他杯状病毒一样,在RdRp-VP60连接处高度保守,在这一点上有利于基因型间重组事件。RCV(基因型GI.3)之间的重组,非结构(NS)基因的供体,还有一种未知的病毒,结构(S)基因的供体,很可能导致欧洲兔子中出现了一种新的拉格病毒,称为RHDV类型2(GI.2),2010年在欧洲确定。在欧洲和澳大利亚的兔子中分离的新的RHDV2基因型间重组体起源于RHDV2(GI.2)和RHDV(GI.1)或RCV(GI.3,4)之间的类似事件。RHDV2(GI.2)在全球范围内迅速传播,取代RHDV,并显示几种lagomorph物种作为次要宿主。RHDV2病毒中的重组事件导致许多具有非常不同的NS和S基因组合的病毒。最近在欧洲野兔中鉴定了具有来自野兔谱系(GII)的NS基因的重组RHDV2。这项研究调查了在欧洲野兔(RHDV2_Bg12)中在意大利确定的第一个RHDV2(GI.2),证明这是一种新病毒,起源于作为S基因供体的RHDV2和野兔lagovirus之间的重组,尚未确定,但可能是非致病性的,作为NS基因供体。当兔子接种RHDV2_Bg12时,既没有死亡也没有血清转化记录,证明RHDV2_Bg12不能感染兔子。此外,尽管密集和连续的现场监测,RHDV2_Bg12从未在意大利或其他地方的野兔或兔子中再次被发现。这一结果表明,lagovirus的宿主特异性不仅可以依赖于S基因,正如预期的那样,直到今天,但也可能在一些物种特异性NS基因序列上。因此,因为RHDV2(GI.2)感染了几种Lagomorphs,反过来可能含有几种特定的非致病性泻药病毒,新物种形成的可能性,尤其是兔子以外的动物,是真实的。RHDV2Bg_12证明了这一点,虽然这次尝试显然失败了。
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