Müller Claudia, Hrynkiewicz Rafał, Bębnowska Dominika, Maldonado Jaime, Baratelli Massimiliano, Köllner Bernd, Niedźwiedzka-Rystwej Paulina
Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institute, 17493 Greifswald-Insel Riems, Germany.
Institute of Biology, University of Szczecin, Felczaka 3c, 71-412 Szczecin, Poland.
Vaccines (Basel). 2021 Mar 13;9(3):255. doi: 10.3390/vaccines9030255.
In the early 1980s, a highly contagious viral hemorrhagic fever in rabbits () emerged, causing a very high rate of mortality in these animals. Since the initial occurrence of the rabbit hemorrhagic disease virus (RHDV), several hundred million rabbits have died after infection. The emergence of genetically-different virus variants (RHDV GI.1 and GI.2) indicated the very high variability of RHDV. Moreover, with these variants, the host range broadened to hare species (). The circulation of RHDV genotypes displays different virulences and a limited induction of cross-protective immunity. Interestingly, juvenile rabbits (<9 weeks of age) with an immature immune system display a general resistance to RHDV GI.1, and a limited resistance to RHDV GI.2 strains, whereas less than 3% of adult rabbits survive an infection by either RHDV GI.1. or GI.2. Several not-yet fully understood phenomena characterize the RHD. A very low infection dose followed by an extremely rapid viral replication could be simplified to the induction of a disseminated intravascular coagulopathy (DIC), a severe loss of lymphocytes-especially T-cells-and death within 36 to 72 h post infection. On the other hand, in animals surviving the infection or after vaccination, very high titers of RHDV-neutralizing antibodies were induced. Several studies have been conducted in order to deepen the knowledge about the virus' genetics, epidemiology, RHDV-induced pathology, and the anti-RHDV immune responses of rabbits in order to understand the phenomenon of the juvenile resistance to this virus. Moreover, several approaches have been used to produce efficient vaccines in order to prevent an infection with RHDV. In this review, we discuss the current knowledge about anti-RHDV resistance and immunity, RHDV vaccination, and the further need to establish rationally-based RHDV vaccines.
20世纪80年代初，一种传染性极强的兔病毒性出血热出现，导致这些动物的死亡率极高。自兔出血症病毒（RHDV）首次出现以来，数亿只兔子感染后死亡。基因不同的病毒变体（RHDV GI.1和GI.2）的出现表明RHDV具有很高的变异性。此外，随着这些变体的出现，宿主范围扩大到野兔物种。RHDV基因型的传播表现出不同的毒力，且诱导交叉保护性免疫的能力有限。有趣的是，免疫系统不成熟的幼兔（<9周龄）对RHDV GI.1具有普遍抗性，对RHDV GI.2毒株具有有限抗性，而成年兔感染RHDV GI.1或GI.2后存活的比例不到3%。有几种尚未完全理解的现象是兔出血症的特征。极低的感染剂量后紧接着病毒极快速的复制，这可简化为诱导弥散性血管内凝血（DIC）、淋巴细胞尤其是T细胞的严重损失以及感染后36至72小时内死亡。另一方面，在感染后存活或接种疫苗的动物中，会诱导产生非常高滴度的RHDV中和抗体。为了加深对该病毒的遗传学、流行病学、RHDV诱导的病理学以及兔抗RHDV免疫反应的了解，以便理解幼兔对该病毒具有抗性的现象，已经开展了多项研究。此外，已经采用了几种方法来生产高效疫苗，以预防RHDV感染。在本综述中，我们讨论了关于抗RHDV抗性和免疫、RHDV疫苗接种的现有知识，以及进一步建立基于合理依据的RHDV疫苗的必要性。
