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

Rabbit hemorrhagic 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 5 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 3 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 2 of 5 ECTs infected with RHDV2. One ECT inoculated with RHDV2 seroconverted and developed a high antibody titer by the end of the experimental period (21 DPI). Eastern cottontails inoculated with the classic RHDV did not seroconvert. In comparison, NZWRs inoculated with RHDV2 exhibited high mortality (5 of 5) at 2 DPI and 4 of 5 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. This article is protected by copyright. All rights reserved.