Genetic variability and phylogenetic analysis of Lagovirus europaeus strains GI.1 (RHDV) and GI.2 (RHDV2) based on the RNA-dependent RNA polymerase (RdRp) coding gene

Abstract

Lagovirus europaeus GI.1 (RHDV-rabbit haemorrhagic disease virus) and GI.2 (RHDV2-rabbit haemorrhagic disease virus 2), family Caliciviridae, genus Lagovirus, are etiological factors of the rabbit haemorrhagic disease (RHD). This small RNA virus is a great model for tracking the variability and evolution of RNA viruses, because it uses an RNA-dependent RNA polymerase (RdRp) to replicate its own genetic material. This polymerase determines the fidelity and the rates of replication and mutation of the virus, conditioning its adaptation to the environment and even to a new host, and thus influencing evolution of the virus. The aim of this study was to determine the genetic variability and phylogenetic relationships of 105 Lagovirus europaeus strains with different genotypes based on the RdRp gene. The strains came from around the world in the years of 1987–2017. The aforementioned group of 105 strains included 14 strains whose RdRp sequences were obtained and analysed in this study, and the rest were retrieved from GenBank: 74 strains classified as genotype GI.1 (RHDV), 14 as GI.2 (RHDV2), 2 strains of Lagovirus europaeus not assigned to any genotype, and a MRCV strain, the sequences of which were collected from GenBank. Among the 14 strains whose RdRp sequences were obtained in this study, the highest variability was presented in the Austrian 237 strain from 2004. The genetic distance between the Austrian 237 strain and the remaining thirteen analysed strains ranged from 0.117 to 0.123 (from 11.7% to 12.3% nucleotide substitutions). The lowest variability, however, was recorded for Hungarian, Czech and Austrian strains. On the phylogenetic tree, the 14 analysed strains were allocated into GI.1c (G2), GI.1d (G3-G5) and GI.1a (RHDVa). Analysis of the genetic variability of the 105 strains of Lagovirus europaeus indicated a growing genetic distance between the strains, both in time and location. Phylogenetic analysis showed a division of the strains into seven groups, dictated by the chronology, geographical location and evolutionary events in the history of the virus, such as mutations and recombinations.

Changes in MicroRNA Expression during Rabbit Hemorrhagic Disease Virus (RHDV) Infection

“…It was first reported in China in 1984 in rabbits imported from Germany and spread over the entire country in less than a year, causing large-scale rabbit deaths [2]. The main driving force behind the genetic variability of this virus is RNA-dependent RNA polymerase (RdRp) [3]. This enzyme determines the virus's fidelity, as well as the speed of its replication and mutation, and conditions its adaptation to the environment and new hosts.…”

“…An analysis of the genetic variability of Lagovirus europaeus GI.1 (RHDV) and GI.2 (RHDV2) on the basis of the RdRp coding gene indicated growing genetic variability between the strains, both in time and location. Moreover, phylogenetic analysis showed a division of the 105 strains Lagovirus europaeus into seven groups, determined by their chronology, geographical location, and evolutionary events, such as mutation and recombinations [3]. Currently, this disease affects rabbit populations worldwide, and although more than 30 years have passed since the first outbreak of rabbit hemorrhagic disease, the mechanisms underlying the pathogenesis of the disease are not yet fully understood.…”

Potential therapeutic targets and promising drugs for combating SARS‐CoV‐2

“…During the replication process of RNA viruses, RdRP determines the fidelity and the rates of replication and mutation of the virus to condition its adaptation to the environment and even to a new host, thus influencing the evolution of the virus (Hukowska‐Szematowicz, 2020). Targeting RdRP has become recognized as one of the most important means for the treatment of SARS‐CoV.…”

Nano-Biomimetic Drug Delivery Vehicles: Potential Approaches for COVID-19 Treatment

“…Papain-like cysteine protease (PLpro) and 3C-like serine protease (3CLpro or Mpro) viral enzymes are implicated in the delivery of non-structural proteins, including RNA-dependent RNA polymerase (RdRp) and helicase, which are involved in the process of transcription and replication of the virus [75,76]. Potential therapeutic compounds which inhibit 3CLpro and PLpro may be explored for the treatment of COVID-19 infections.…”