Citation: Hall, R.N.; Trought, K.; Strive, T.; Duckworth, J.A.; Jenckel, M. First Detection and Circulation of RHDV2 in New Zealand. Viruses 2024, 16, 519. https://doi.org/10.3390/ v16040519 Academic Editors: Pedro José Castro Esteves, Joana Abrantes and Ana M. Lopes Received: 27 February 2024 Revised: 19 March 2024 Accepted: 26 March 2024 Published: 28 March 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). viruses Article First Detection and Circulation of RHDV2 in New Zealand Robyn N. Hall 1,2,3 , Katherine Trought 4 , Tanja Strive 1,2 , Janine A. Duckworth 4 and Maria Jenckel 1, * 1 CSIRO Health & Biosecurity, Acton, ACT 2601, Australia; tanja.strive@csiro.au 2 Centre for Invasive Species Solutions, Bruce, ACT 2617, Australia 3 Ausvet Pty Ltd., Fremantle, WA 6160, Australia; robyn.hall@ausvet.com.au 4 Manaaki Whenua-Landcare Research, Lincoln 7608, New Zealand; troughtk@landcareresearch.co.nz (K.T.); duckworthj@landcareresearch.co.nz (J.A.D.) * Correspondence: maria.jenckel@csiro.au Abstract: Rabbit haemorrhage disease virus 2 (RHDV2) is a highly pathogenic lagovirus that causes lethal disease in rabbits and hares (lagomorphs). Since its first detection in Europe in 2010, RHDV2 has spread worldwide and has been detected in over 35 countries so far. Here, we provide the first detailed report of the detection and subsequent circulation of RHDV2 in New Zealand. RHDV2 was first detected in New Zealand in 2018, with positive samples retrospectively identified in December 2017. Subsequent time-resolved phylogenetic analysis suggested a single introduction into the North Island between March and November 2016. Genetic analysis identified a GI.3P-GI.2 variant supporting a non-Australian origin for the incursion; however, more accurate identification of the source of the incursion remains challenging due to the wide global distribution of the GI.3P-GI.2 variant. Furthermore, our analysis suggests the spread of the virus between the North and South Islands of New Zealand at least twice, dated to mid-2017 and around 2018. Further phylogenetic analysis also revealed a strong phylogeographic pattern. So far, no recombination events with endemic benign New Zealand rabbit caliciviruses have been identified. This study highlights the need for further research and surveillance to monitor the distribution and diversity of lagoviruses in New Zealand and to detect incursions of novel variants. Keywords: European rabbit; Oryctolagus cuniculus; invasive species; RHDV2; viral pathogens 1. Introduction Rabbit haemorrhagic disease virus 2 (RHDV2, or genotype GI.2 [1]) is a lagovirus in the family Caliciviridae that first emerged in France in 2010 [2,3]. Like the closely related RHDV1 (genotype GI.1c), it causes an acute, fulminant hepatitis and severe multisystemic inflammatory response leading to disseminated intravascular coagulation and death within 36–72 h after infection [4]. However, unlike RHDV1, RHDV2 is lethal in young rabbits that are typically only subclinically infected with RHDV1 [2,5]. Moreover, apart from European rabbits (Oryctolagus cuniculus), RHDV2 can infect other lagomorphs, such as hares and jackrabbits (Lepus sp.) and cottontails (Sylvilagus sp.) [1,6–14]. RHDV2 is truly an emerging, panzootic virus. Between 2010 and 2021, RHDV2 incursions were reported by over 35 countries globally (Figure 1). RHDV2 can (at least partially) overcome immunity against prior RHDV1 infection and vaccination [5,15]; it has a broader host range than RHDV1 [1,6–14]; and it appears to enter susceptible rabbit populations earlier than RHDV1 variants [16]. Taken together, these factors begin to explain the rapid spread of RHDV2 and the corresponding epidemiological replacement of the previously dominant RHDV1 variants. Lagoviruses are small non-enveloped viruses of about 25–40 nm in diameter [17–19]. The RHDV genome is about 7.5 kb in size and encodes both structural proteins (VP60 and VP10, which form the virus capsid) and non-structural (NS) proteins (from the 5 ′ -end: p16, p23, helicase, p29, viral protein genome-linked (VPg), protease, and RNA-dependent RNA Viruses 2024, 16, 519. https://doi.org/10.3390/v16040519 https://www.mdpi.com/journal/viruses