Estimating evolutionary changes between highly passaged and original parental lumpy skin disease virus strains

Abstract

Research into the phylogenetic relationships of lumpy skin disease virus (LSDV) strains was long overlooked, partially due to its original restricted distribution to sub‐Saharan Africa. However, recent incursions into northern latitudes, and a rapid spread causing major economic losses worldwide, have intensified additional research on the disease and the causative virus. This study delineates the phylogeny of LSDV in the context of full genome sequences of strains recovered in the field, as well as strains highly passaged in cell culture. We sequenced the oldest known field strain to date (isolate LSDV/Haden/RSA/1954 [South Africa] recovered from an outbreak in 1954), a recent field isolate (LSDV/280‐KZN/RSA/2018 [South Africa] sequenced directly from blood during an outbreak in 2018) and strain LSDV/Russia/Dagestan‐75 (a high‐passaged cell culture strain derived from the field strain, LSDV/Russia/Dagestan/2015 [Russia]). Sequence analysis placed the field strain LSDV/Haden/RSA/1954 in the same cluster (cluster 1.1) with attenuated Neethling‐type commercial vaccine viruses, with eight SNP differences, discrediting the previously held hypothesis that cluster 1.1 vaccine strains were derived from cluster 1.2 field viruses via the process of attenuation between them. In contrast, the recent LSDV/280‐KZN/RSA/2018 isolate grouped with other recent field isolates in cluster 1.2, providing evidence that cluster 1.1 strains were displaced by cluster 1.2 strains in South Africa. Based on the field isolates between 1954 and 2018, the substitution rate of 7.4 × 10–6 substitutions/site/year was established, with mutations occurring in either synonymous sites or intergenic regions. This is the first evolutionary metric recorded for LSDV. Comparing the genome sequences of high‐passage strains of LSDV showed that propagation in vitro without animal host selective pressure generates mainly non‐synonymous SNPs in virus‐replication genes. These results improve our understanding of LSDV evolution and demonstrate that the population dynamics of circulating isolates is not constant, with LSDV associated with different genetic clusters dominating the landscape during specific periods in time.

Overwintering of recombinant lumpy skin disease virus in northern latitudes, Russia

“…The majority of the SNPs were located within the IGRs, while the majority of SNPs in ORFs were synonymous. This corresponds to previous descriptions of genetic drift in LSDVs (van Schalkwyk et al., 2022). Since all the nonsynonymous SNPs were confined to three ORFs, it indicates the selective pressure exerted on these ORFs and their possible importance in virus fitness, host selection or virus transmission.…”

“…A recent increase in publically available complete genome sequences of LSDV strains, has led to the phylogenetic clustering of these viruses into three groups. These groups consist of two monophyletic clusters (cluster 1.1 and 1.2) and several novel recombinant viruses (van Schalkwyk et al., 2022). Both cluster 1.1 and cluster 1.2 contain wild‐type viruses isolated during active outbreaks, while cluster 1.1 additionally encompasses the commercially available vaccines based on LSDV/Neethling/LW‐1958 (Sprygin et al., 2019; van Rooyen et al., 1959; van Schalkwyk et al., 2020).…”

Molecular Characterization of the 2020 Outbreak of Lumpy Skin Disease in Nepal

“…From 2012, the disease reached the Middle East, Europe, and South Asia [ 10 ] successively. While the initial LSDV genome in Africa was stable or had minor differences for decades, including for vaccines related field isolates which were only sequenced recently [ 11 ], the field isolates recovered after the transcontinental spread of LSD revealed significant genomic variabilities [ 12 , 13 ]. For instance, the molecular characterization of the field LSDV isolates from Russia and China showed vaccine-like profiles attributable to the recombination events between the Neethling vaccine strain and field isolates related to LSDV KSGPO-240 [ 14 , 15 , 16 ].…”

Molecular characterization of a novel recombinant lumpy skin disease virus isolated during an outbreak in Tyumen, Russia, in 2019

“…In this regard, the observed dynamic and transboundary potential of the disease requires urgent efforts to better understand the fundamental aspects of its nature. The isolates from Africa, the Middle East and Europe, including the first outbreak in the Russian Federation (Russia/Dagestan/2015), could be phylogenetically assigned to two clusters (Cluster 1.1 and 1.2) (Toplak et al., 2017; Agianniotaki et al., 2017; Kononov et al., 2019; Sprygin et al., 2019, 2020a; van Schalkwyk et al., 2020, 2022). In 2017, an outbreak of LSD was reported in the Saratov region of Russia and based on complete genome sequence analysis it proved to be a unique naturally occurring vaccine‐derived recombinant strain (LSDV/Russia/Saratov/2017) (Sprygin et al., 2018).…”