Mutational Signatures and Heterogeneous Host Response Revealed Via Large-scale Characterization of SARS-CoV-2 Genomic Diversity

Overview

Journal iScience

Publisher Cell Press

Date 2021 Feb 3

PMID 33532709

Citations 53

Authors

Alex Graudenzi

Davide Maspero

Fabrizio Angaroni

Rocco Piazza

Daniele Ramazzotti

Affiliations

Soon will be listed here.

Abstract

To dissect the mechanisms underlying the inflation of variants in the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) genome, we present a large-scale analysis of intra-host genomic diversity, which reveals that most samples exhibit heterogeneous genomic architectures, due to the interplay between host-related mutational processes and transmission dynamics. The decomposition of minor variants profiles unveils three non-overlapping mutational signatures related to nucleotide substitutions and likely ruled by APOlipoprotein B Editing Complex (APOBEC), Reactive Oxygen Species (ROS), and Adenosine Deaminase Acting on RNA (ADAR), highlighting heterogeneous host responses to SARS-CoV-2 infections. A corrected-for-signatures analysis demonstrates that such mutational processes are affected by purifying selection, with important exceptions. In fact, several mutations appear to transit toward clonality, defining new clonal genotypes that increase the overall genomic diversity. Furthermore, the phylogenomic analysis shows the presence of homoplasies and supports the hypothesis of transmission of minor variants. This study paves the way for the integrated analysis of intra-host genomic diversity and clinical outcomes of SARS-CoV-2 infections.

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