Viral haemorrhagic disease: RHDV type 2 ten years later
Authors: Capucci Lorenzo , Cavadini Patrizia , Lavazza Antonio 
Published: March 2022

Until the early 1980s, it was totally unknown that lagomorphs were the hosts of several caliciviruses, which were included in the genus Lagovirus by the International Committee on Taxonomy of Viruses (ICTV) in 2000. In those years, two new diseases appeared, with very similar clinical and pathological profiles and associated high mortality rates: rabbit haemorrhagic disease (RHD) in rabbits and European Brown Hare Syndrome (EBHS) in European brown hares. It took a few years to ascertain that both diseases, actually acute and fatal forms of hepatitis, were caused by two genetically related caliciviruses, but they were finally classified by ICTV into two distinct viral species on the basis of their molecular characterisation and epidemiological data: RHDV in rabbit and EBHSV in brown hare. RHD has had a devastating effect on rabbit farms, causing great economic damage, especially in China, where RHD was first noticed around 1982, and in Europe. RHD has also severely affected wild rabbit populations, whose drastic decline has caused serious ecological imbalances in territories such as Spain, where rabbits are a central link in the wildlife food chain. Since the early 1990s, with the increased availability on the market of RHDV vaccines effective in protecting rabbits from RHD, the impact of the disease on rabbit farms has been significantly reduced. In the following years, also considering that RHDV is an endemic virus that cannot be eradicated, farmers learned how to manage the continuous use of RHDV vaccine in relation to the epidemiological situation, the type of breeding farm and the costs of vaccination prophylaxis. Although precarious, management of the RHD risk for rabbit farmers reached an acceptable equilibrium, which was, however, completely upset starting from 2010 by the emergence of another lagovirus also causing RHD. The genome of the newly emerged virus shows limited differences from that of RHDV, but the phenotypic traits of the two viruses are distinctive in at least three main respects: 1) The antigenic profile of the virus (the “face” of the virus recognised by the antibodies) is largely different from that of RHDV. 2) Newborn rabbits only a couple of weeks old die of RHD when infected with the new virus, while RHDV infections run asymptomatic until 7-8 wk of age. 3) The new virus, which started in Europe, has spread over the years to several continents, affecting wild and/or domestic rabbit populations. During this worldwide distribution, the new virus infected several lagomorph species and was shown to cause RHD in most of them. Considering these marked differences and the fact that the new virus is not a variant of RHDV, we proposed the name RHDV type 2 (RHDV2). All these main distinctive traits that differentiate RHDV from RHDV2 have the following consequences in practice: 1) The antigenic difference between RHDV and RHDV2 (their ‘faces’) is so great that we need “new” specific vaccines to control RHDV2 (i.e. RHDV2 is a new serotype). 2) In the event of an RHDV2 infection in suckling rabbits, the presence of maternal antibodies to RHDV2 in the blood is the only way to prevent RHD. In contrast, newborns are naturally resistant to RHD if infected with RHDV and therefore, in terms of protection, the presence of maternal antibodies is useless. 3) When RHD outbreaks occur in territories where rabbits live in sympatry with populations of other lagomorphs, viral contamination in the environment reaches sufficiently high levels to facilitate the transmission of RHDV2 to other lagomorphs, including those with a lower susceptibility to infection than the rabbit. Taken together, these phenotypic traits characteristic of RHDV2 are the reason for its rapid spread across the territory and the concomitant disappearance of RHDV. Probably the most striking example of the epidemiological consequences related to the peculiar features of RHDV2 is its rapid spread in the USA and Mexico, where it is now practically endemic. There, despite repeated isolated outbreaks of RHD caused by RHDV from 2000 onwards in small rabbit farms, RHDV has never been able to become endemic.