Comparative susceptibility of eastern cottontails and New Zealand white rabbits to classical rabbit haemorrhagic disease virus (RHDV) and RHDV2

Abstract

Rabbit haemorrhagic disease virus (RHDV) is associated with high morbidity and mortality in the European rabbit (Oryctolagus cuniculus). In 2010, a genetically distinct RHDV named RHDV2 emerged in Europe and spread to many other regions, including North America in 2016. Prior to this study it was unknown if eastern cottontails (ECT(s); Sylvilagus floridanus), one of the most common wild lagomorphs in the United States, were susceptible to RHDV2. In this study, 10 wild-caught ECTs and 10 New Zealand white rabbits (NZWR(s); O. cuniculus) were each inoculated orally with either RHDV (RHDVa/GI.1a; n = 5 per species) or RHDV2 (a recombinant GI.1bP-GI.2; n = 5 per species) and monitored for the development of disease. Three of the five ECTs that were infected with RHDV2 developed disease consistent with RHD and died at 4 and 6 days post-inoculation (DPI). The RHDV major capsid protein/antigen (VP60) was detected in the livers of three ECTs infected with RHDV2, but none was detected in the ECTs infected with RHDV. Additionally, RHD viral RNA was detected in the liver, spleen, intestine and blood of ECTs infected with RHDV2, but not in the ECTs infected with RHDV. RHD viral RNA was detected in urine, oral swabs and rectal swabs in at least two of five ECTs infected with RHDV2. One ECT inoculated with RHDV2 seroconverted and developed a high antibody titre by the end of the experimental period (21 DPI). ECTs inoculated with the classic RHDV did not seroconvert. In comparison, NZWRs inoculated with RHDV2 exhibited high mortality (five of five) at 2 DPI and four of five NZWRs inoculated with RHDV either died or were euthanized at 2 DPI indicating both of these viruses were highly pathogenic to this species. This experiment indicates that ECTs are susceptible to RHDV2 and can shed viral RNA, thereby suggesting this species could be involved in the epidemiology of this virus.

A novel vaccine candidate against rabbit hemorrhagic disease virus 2 (RHDV2) confers protection in domestic rabbits

“…15 Furthermore, cottontails (Sylvilagus spp), which are susceptible to disease but do not always die after infection, are prolific across the country and can be in close contact with domestic rabbits in certain situations, particularly those that live as pets in backyards. 4 Clearly, the best means of preventing mortality is vaccination, and the lack of a readily available vaccine in the United States is concerning for rabbitries, pet owners, and wildlife managers. Thus, the vaccine described herein is timely and will be useful to prevent further infections of rabbits in the United States.…”

“…3 Disturbingly, RHDV2 has a wider host range than classic RHDV, encompassing varieties of wild rabbits previously thought to be unaffected by RHDV, including European and other hares (Lepus spp) and wild rabbits native to the American continent within the genus Sylvilagus. [2][3][4][5] In 2016, the first cases of RHDV2 were reported in North America. The virus was initially detected in…”

Early circulation of rabbit haemorrhagic disease virus type 2 in domestic and wild lagomorphs in southern California, USA (2020–2021)

“…(2015) detected an EBHSV‐infected eastern cottontail during an EBHS outbreak in Italy, and subsequently reproduced the disease in one out of four eastern cottontails inoculated with EBHSV, but not in those inoculated with classic RHDV. A recent study performed at Plum Island Animal Disease Center (New York, USA) with eastern cottontails demonstrated that this species is susceptible to RHDV2, since three out of five experimentally infected individuals died with typical lesions and both viral RNA and antigen were detectable in several tissues (Mohamed et al., 2018). Our data are still limited, but suggest that desert cottontails develop disease when they are naturally infected with RHDV2; however, a certain degree of resistance in animals of the genus Sylvilagus cannot be totally excluded.…”

Rabbit Haemorrhagic Disease Virus 2 (RHDV2; GI.2) in Ireland Focusing on Wild Irish Hares (Lepus timidus hibernicus): An Overview of the First Outbreaks and Contextual Review

“…At least some of the variation in the reported mortality rates for RHDV2 may be related to host age and infectious dose [ 29 ]. However, recent experimental work suggests that the case fatality rate can reach 100% in rabbits [ 20 , 32 ]. Mohamed et al [ 32 ] undertook a comparative experimental study on the effects of RHDV2 on wild caught eastern cottontail ( Sylvilagus floridanus ) relative to New Zealand white rabbits (NZWR), and demonstrated that cottontails had lower disease-induced mortality in comparison with NZWR.…”

“…Animals typically die within 48–96 hours of being exposed to the pathogen. The viral load is high in infected animals that succumb, based on the low Ct value observed by real-time reverse transcription–polymerase chain reaction (RT-PCR) (e.g., [ 32 ]). Death without clinical signs can occur.…”