Dataset Information

Potential neuroinvasive and neurotrophic properties of SARS-CoV-2 in pediatric patients: comparison of SARS-CoV-2 with non-segmented RNA viruses.

ABSTRACT: The emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing global health crises. Children can be infected, but are less likely to develop severe neurological abnormalities compared with adults. However, whether SARS-CoV-2 can directly cause neurological impairments in pediatric patients is not known. The possible evolutionary and molecular relationship between SARS-CoV-2 and non-segmented RNA viruses were examined with reference to neurological disorders in pediatric patients. SARS-CoV-2 shares similar functional domains with neuroinvasive and neurotropic RNA viruses. The Spike 1 (S1) receptor binding domain and the cleavage sites at S1/S2 boundary are less conserved compared with the S2 among coronaviruses.

SUBMITTER: Chen X

PROVIDER: S-EPMC7556565 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Potential neuroinvasive and neurotrophic properties of SARS-CoV-2 in pediatric patients: comparison of SARS-CoV-2 with non-segmented RNA viruses.

Chen Xiaodi X

Journal of neurovirology 20201014 6

The emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing global health crises. Children can be infected, but are less likely to develop severe neurological abnormalities compared with adults. However, whether SARS-CoV-2 can directly cause neurological impairments in pediatric patients is not known. The possible evolutionary and molecular relationship between SARS-CoV-2 and non-segmented RNA viruses were examined with reference to neurological disorders in pediatric pa ...[more]

PMID: 33057966

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Project description:It is generally thought that the promoters of non-segmented, negative strand RNA viruses (nsNSVs) direct the polymerase to initiate RNA synthesis exclusively opposite the 3´ terminal nucleotide of the genome RNA by a de novo (primer independent) initiation mechanism. However, recent studies have revealed that there is diversity between different nsNSVs with pneumovirus promoters directing the polymerase to initiate at positions 1 and 3 of the genome, and ebolavirus polymerases being able to initiate at position 2 on the template. Studies with other RNA viruses have shown that polymerases that engage in de novo initiation opposite position 1 typically have structural features to stabilize the initiation complex and ensure efficient and accurate initiation. This raised the question of whether different nsNSV polymerases have evolved fundamentally different structural properties to facilitate initiation at different sites on their promoters. Here we examined the functional properties of polymerases of respiratory syncytial virus (RSV), a pneumovirus, human parainfluenza virus type 3 (PIV-3), a paramyxovirus, and Marburg virus (MARV), a filovirus, both on their cognate promoters and on promoters of other viruses. We found that in contrast to the RSV polymerase, which initiated at positions 1 and 3 of its promoter, the PIV-3 and MARV polymerases initiated exclusively at position 1 on their cognate promoters. However, all three polymerases could recognize and initiate from heterologous promoters, with the promoter sequence playing a key role in determining initiation site selection. In addition to examining de novo initiation, we also compared the ability of the RSV and PIV-3 polymerases to engage in back-priming, an activity in which the promoter template is folded into a secondary structure and nucleotides are added to the template 3´ end. This analysis showed that whereas the RSV polymerase was promiscuous in back-priming activity, the PIV-3 polymerase generated barely detectable levels of back-primed product, irrespective of promoter template sequence. Overall, this study shows that the polymerases from these three nsNSV families are fundamentally similar in their initiation properties, but have differences in their abilities to engage in back-priming.

Project description:A new word, phylodynamics, was coined to emphasize the interconnection between phylogenetic properties, as observed for instance in a phylogenetic tree, and the epidemic dynamics of viruses, where selection, mediated by the host immune response, and transmission play a crucial role. The challenges faced when investigating the evolution of RNA viruses call for a virtuous loop of data collection, data analysis and modeling. This already resulted both in the collection of massive sequences databases and in the formulation of hypotheses on the main mechanisms driving qualitative differences observed in the (reconstructed) evolutionary patterns of different RNA viruses. Qualitatively, it has been observed that selection driven by the host immune response induces an uneven survival ability among co-existing strains. As a consequence, the imbalance level of the phylogenetic tree is manifestly more pronounced if compared to the case when the interaction with the host immune system does not play a central role in the evolutive dynamics. While many imbalance metrics have been introduced, reliable methods to discriminate in a quantitative way different level of imbalance are still lacking. In our work, we reconstruct and analyze the phylogenetic trees of six RNA viruses, with a special emphasis on the human Influenza A virus, due to its relevance for vaccine preparation as well as for the theoretical challenges it poses due to its peculiar evolutionary dynamics. We focus in particular on topological properties. We point out the limitation featured by standard imbalance metrics, and we introduce a new methodology with which we assign the correct imbalance level of the phylogenetic trees, in agreement with the phylodynamics of the viruses. Our thorough quantitative analysis allows for a deeper understanding of the evolutionary dynamics of the considered RNA viruses, which is crucial in order to provide a valuable framework for a quantitative assessment of theoretical predictions.

Dataset Information

Potential neuroinvasive and neurotrophic properties of SARS-CoV-2 in pediatric patients: comparison of SARS-CoV-2 with non-segmented RNA viruses.

Publications

Potential neuroinvasive and neurotrophic properties of SARS-CoV-2 in pediatric patients: comparison of SARS-CoV-2 with non-segmented RNA viruses.

Similar Datasets

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