Dataset Information

Genomic Diversity and Evolution of Quasispecies in Newcastle Disease Virus Infections.

ABSTRACT: Newcastle disease virus (NDV) infections are well known to harbour quasispecies, due to the error-prone nature of the RNA polymerase. Quasispecies variants in the fusion cleavage site of the virus are known to significantly change its virulence. However, little is known about the genomic patterns of diversity and selection in NDV viral swarms. We analyse deep sequencing data from in vitro and in vivo NDV infections to uncover the genomic patterns of diversity and the signatures of selection within NDV swarms. Variants in viruses from in vitro samples are mostly localised in non-coding regions and 3' and 5' untranslated regions (3'UTRs or 5'UTRs), while in vivo samples contain an order of magnitude more variants. We find different patterns of genomic divergence and diversity among NDV genotypes, as well as differences in the genomic distribution of intra-host variants among in vitro and in vivo infections of the same strain. The frequency spectrum shows clear signatures of intra-host purifying selection in vivo on the matrix protein (M) coding gene and positive or diversifying selection on nucleocapsid (NP) and haemagglutinin-neuraminidase (HN). The comparison between within-host polymorphisms and phylogenetic divergence reveals complex patterns of selective pressure on the NDV genome at between- and within-host level. The M sequence is strongly constrained both between and within hosts, fusion protein (F) coding gene is under intra-host positive selection, and NP and HN show contrasting patterns: HN RNA sequence is positively selected between hosts while its protein sequence is positively selected within hosts, and NP is under intra-host positive selection at the RNA level and negative selection at the protein level.

SUBMITTER: Jadhav A

PROVIDER: S-EPMC7698180 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genomic Diversity and Evolution of Quasispecies in Newcastle Disease Virus Infections.

Jadhav Archana A Zhao Lele L Liu Weiwei W Ding Chan C Nair Venugopal V Ramos-Onsins Sebastian E SE Ferretti Luca L

Viruses 20201114 11

Newcastle disease virus (NDV) infections are well known to harbour quasispecies, due to the error-prone nature of the RNA polymerase. Quasispecies variants in the fusion cleavage site of the virus are known to significantly change its virulence. However, little is known about the genomic patterns of diversity and selection in NDV viral swarms. We analyse deep sequencing data from in vitro and in vivo NDV infections to uncover the genomic patterns of diversity and the signatures of selection with ...[more]

PMID: 33202558

Similar Datasets

Project description:UnlabelledIt has been reported that lentogenic Newcastle disease virus (NDV) isolates have the potential to become velogenic after their transmission and circulation in chickens, but the underlying mechanism is unclear. In this study, a highly velogenic NDV variant, JS10-A10, was generated from the duck-origin lentogenic isolate JS10 through 10 consecutive passages in chicken air sacs. The velogenic properties of this selected variant were determined using mean death time (MDT) assays, intracerebral pathogenicity index (ICPI), the intravenous pathogenicity index (IVPI), histopathology, and the analysis of host tissue tropism. In contrast, JS10 remained lentogenic after 20 serial passages in chicken eggs (JS10-E20). The JS10, JS10-A10, and JS10-E20 genomes were sequenced and found to be nearly identical, suggesting that both JS10-A10 and JS10-E20 were directly generated from JS10. To investigate the mechanism for virulence enhancement, the partial genome covering the F0 cleavage site of JS10 and its variants were analyzed using ultradeep pyrosequencing (UDPS) and the proportions of virulence-related genomes in the quasispecies were calculated. Velogenic NDV genomes accumulated as a function of JS10 passaging through chicken air sacs. Our data suggest that lentogenic NDV strains circulating among poultry might be a risk factor to future potential velogenic NDV outbreaks in chickens.ImportanceAn avirulent isolate, JS10, was passaged through chicken air sacs and embryos, and the pathogenicity of the variants was assessed. A virulent variant, JS10-A10, was generated from consecutive passage in air sacs. We developed a deep-sequencing approach to detect low-frequency viral variants across the NDV genome. We observed that virulence enhancement of JS10 was due to the selective accumulation of velogenic quasispecies and the concomitant disappearance of lentogenic quasispecies. Our results suggest that because it is difficult to avoid contact between natural waterfowl reservoirs and sensitive poultry operations, circulating lentogenic NDV strains may represent a potential reservoir for emergent velogenic NDV strains that could cause outbreaks in chickens.

Project description:Numerous factors have been identified to influence susceptibility to SARS-CoV-2 infection and disease severity. Cancer patients are more prone to clinically evolve to more severe COVID-19 conditions, but the determinants of such a more severe outcome remain largely unknown. We have determined the full-length SARS-CoV-2 genomic sequences of cancer patients and healthcare workers (HCW; non-cancer controls) by deep sequencing and investigated the within-host viral quasispecies of each infection, quantifying intrahost genetic diversity. Naso- and oropharyngeal SARS-CoV-2 + swabs from 57 cancer patients and 14 healthcare workers (HCW) from the Brazilian Cancer Institute were collected in April-May 2020. Complete genome amplification using ARTIC network V3 multiplex primers was performed followed by next-generation sequencing. Assemblies were conducted in Geneious R11, where consensus sequences were extracted and intrahost single nucleotide variants (iSNVs) were identified. Maximum likelihood phylogenetic analysis was performed using PhyMLv.3.0 and lineages were classified using Pangolin and CoV-GLUE. Phylogenetic analysis showed that all but one strain belonged to clade B1.1. Four genetically linked mutations known as the globally dominant SARS-CoV-2 haplotype (C241T, C3037T, C14408T and A23403G) were found in the majority of consensus sequences. SNV signatures of previously characterized Brazilian genomes were also observed in most samples. Another 85 SNVs were found at a lower frequency (1.4-19.7%). Cancer patients displayed a significantly higher intrahost viral genetic diversity compared to HCW (p = 0.009). Intrahost genetic diversity in cancer patients was independent of SARS-CoV-2 Ct values, and was not associated with disease severity, use of corticosteroids, or use of antivirals, characteristics that could influence viral diversity. Such a feature may explain, at least in part, the more adverse outcomes to which cancer/COVID-19 patients experience. Author Summary:Cancer patients are more prone to clinically evolve to more severe COVID-19 conditions, but the determinants of such a more severe outcome remain largely unknown. In this study, phylogenetic and variation analysis of SARS-CoV-2 genomes from cancer patients and non-cancer healthcare workers at the Brazilian National Cancer Institute were characterized by deep sequencing. Viral genomes showed signatures characteristic of Brazilian viruses, consistent with the hypothesis of local, community transmission rather than virus importation from abroad. Despite most genomes in patients and healthcare workers belonging to the same lineage, intrahost variability was higher in cancer patients when compared to non-cancer counterparts. The intrahost genomic diversity analysis presented in our study highlights the relaxed evolution of SARS-CoV-2 in a vulnerable population of cancer patients. The high number of minor variations can result in the selection of immune escape variants, resistance to potential drugs, and/or increased pathogenicity. The impact of this higher intrahost variability over time warrants further investigation.

Dataset Information

Genomic Diversity and Evolution of Quasispecies in Newcastle Disease Virus Infections.

Publications

Genomic Diversity and Evolution of Quasispecies in Newcastle Disease Virus Infections.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets