Genome sequencing of an Indian peste des petits ruminants virus isolate, Izatnagar/94, and its implications for virus diversity, divergence and phylogeography

Abstract

Peste des petits ruminants is an important transboundary disease infecting small ruminants. Genome or gene sequence analysis enriches our knowledge about the evolution and transboundary nature of the causative agent of this disease, peste des petits ruminants virus (PPRV). Although analysis using whole genome sequences of pathogens leads to more precise phylogenetic relationships, when compared to individual genes or partial sequences, there is still a need to identify specific genes/genomic regions that can provide evolutionary assessments consistent with those predicted with full-length genome sequences. Here the virulent Izatnagar/94 PPRV isolate was assembled and compared to all available complete genome sequences (currently in the NCBI database) to estimate nucleotide diversity and to deduce evolutionary relationships between genes/genomic regions and the full length genomes. Our aim was to identify the preferred candidate gene for use as a phylogenetic marker, as well as to predict divergence time and explore PPRV phylogeography. Among all the PPRV genes, the H gene was identified to be the most diverse with the highest evolutionary relationship with the full genome sequences. Hence it is considered as the most preferred candidate gene for phylogenetic study with 93% identity set as a nucleotide cutoff. A whole genome nucleotide sequence cutoff value of 94% permitted specific differentiation of PPRV lineages. All the isolates examined in the study were found to have a most recent common ancestor in the late 19th or in the early 20th century with high posterior probability values. The Bayesian skyline plot revealed a decrease in genetic diversity among lineage IV isolates since the start of the vaccination program and the network analysis localized the ancestry of PPRV to Africa.

A comprehensive global perspective on phylogenomics and evolutionary dynamics of Small ruminant morbillivirus

“…A diverse nucleotide hotspot was obsereved between 5ʹ UTR of M and 3ʹ UTR of the F genes in the whole genome. This aligns with observations made previously where a hotspot was identified at similar position between M and F genes 14 , highlighting potential variations in the genome size and corresponding substitutions 43 in each of the gene. An influence of these spontaneous mutations in genome was assessed by employing Tajima's D statistics that showed a non-significant negative value for all coding genes in DnaSP analysis, suggesting a lack of influence of spontaneous mutations on the fitness of individual virus.…”

“…Contrary to Table 10. Evidence of recombination events in the whole genome of Pakistan-originated SRMV strain along with breakpoint positions and significant p-values current study findings where analysis showed negative value for each of the coding genes, positive values in F and H genes has previously been suggested 14 . The non-synonymous/synonymous rate (ω = dN-dS) is an important indicator of selective pressure at the protein level where ω = 1 means neutral mutations, ω < 1 correspond to purifying selection while ω > 1 indicates diversifying positive pressure 44 .…”

“…Owing to significant roles in attachment and subsequent genome replication, the gene has been proposed to assess the evolutionary relationship of SRMV strains 41 . Though it ascertains further research, the substitutions in the H gene may have an influence on host adaptability and pathogenicity to susceptible host such as observed previously for SRMV 14 and influenza virus 42 . A diverse nucleotide hotspot was obsereved between 5ʹ UTR of M and 3ʹ UTR of the F genes in the whole genome.…”

“…Given the fact that genetic variations within a population of viruses could alter their pathogenicity and host spectrum, viral genetic diversity is considered a key to unleash viral evolution 13 . Using complete or partial sequencing of single genes (H, N or F), the clustering pattern, genomic and residue characteristics of SRMVs have widely been studied and discussed across the globe 5,10,12,14 . However, based upon each of these particular genes, the deduced genomic and residue characteristics may not be considered enough to predict ongoing evolutionary patterns across the whole length of the genome.…”

Modulation of Host miRNAs Transcriptome in Lung and Spleen of Peste des Petits Ruminants Virus Infected Sheep and Goats

“…A highly virulent PPRV (Izatnagar/94 - lineage IV) isolate maintained at PPR Laboratory, Division of Virology, Indian Veterinary Research Institute, Mukteshwar was used as a challenge virus (Sreenivasa et al, 2002). The accession number of this isolate is (KR140086.1; Sahu et al, 2017). Splenic suspension (10%) of virulent virus was inoculated subcutaneously (4 ml suspension, 2 ml each at two different sites).…”