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Nucleic Acids Res ; 50(3): 1551-1561, 2022 02 22.
Article in English | MEDLINE | ID: covidwho-1636373


During the course of the COVID-19 pandemic, large-scale genome sequencing of SARS-CoV-2 has been useful in tracking its spread and in identifying variants of concern (VOC). Viral and host factors could contribute to variability within a host that can be captured in next-generation sequencing reads as intra-host single nucleotide variations (iSNVs). Analysing 1347 samples collected till June 2020, we recorded 16 410 iSNV sites throughout the SARS-CoV-2 genome. We found ∼42% of the iSNV sites to be reported as SNVs by 30 September 2020 in consensus sequences submitted to GISAID, which increased to ∼80% by 30th June 2021. Following this, analysis of another set of 1774 samples sequenced in India between November 2020 and May 2021 revealed that majority of the Delta (B.1.617.2) and Kappa (B.1.617.1) lineage-defining variations appeared as iSNVs before getting fixed in the population. Besides, mutations in RdRp as well as RNA-editing by APOBEC and ADAR deaminases seem to contribute to the differential prevalence of iSNVs in hosts. We also observe hyper-variability at functionally critical residues in Spike protein that could alter the antigenicity and may contribute to immune escape. Thus, tracking and functional annotation of iSNVs in ongoing genome surveillance programs could be important for early identification of potential variants of concern and actionable interventions.

Evolution, Molecular , Genetic Variation/genetics , Genome, Viral/genetics , Host-Pathogen Interactions/genetics , SARS-CoV-2/genetics , APOBEC-1 Deaminase/genetics , Adenosine Deaminase/genetics , Animals , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/virology , Chlorocebus aethiops , Coronavirus RNA-Dependent RNA Polymerase/genetics , Databases, Genetic , Immune Evasion/genetics , India/epidemiology , Phylogeny , RNA-Binding Proteins/genetics , SARS-CoV-2/classification , SARS-CoV-2/growth & development , Spike Glycoprotein, Coronavirus/genetics , Vero Cells
Front Immunol ; 12: 690416, 2021.
Article in English | MEDLINE | ID: covidwho-1317226


The AID (activation-induced cytidine deaminase)/APOBEC (apolipoprotein B mRNA editing enzyme catalytic subunit) family with its multifaceted mode of action emerges as potent intrinsic host antiviral system that acts against a variety of DNA and RNA viruses including coronaviruses. All family members are cytosine-to-uracil deaminases that either have a profound role in driving a strong and specific humoral immune response (AID) or restricting the virus itself by a plethora of mechanisms (APOBECs). In this article, we highlight some of the key aspects apparently linking the AID/APOBECs and SARS-CoV-2. Among those is our discovery that APOBEC4 shows high expression in cell types and anatomical parts targeted by SARS-CoV-2. Additional focus is given by us to the lymphoid structures and AID as the master regulator of germinal center reactions, which result in antibody production by plasma and memory B cells. We propose the dissection of the AID/APOBECs gene signature towards decisive determinants of the patient-specific and/or the patient group-specific antiviral response. Finally, the patient-specific mapping of the AID/APOBEC polymorphisms should be considered in the light of COVID-19.

APOBEC-1 Deaminase/genetics , COVID-19/enzymology , COVID-19/immunology , Cytidine Deaminase/genetics , SARS-CoV-2/genetics , Transcriptome , Antibodies, Viral/immunology , B-Lymphocytes/immunology , COVID-19/virology , Germinal Center/immunology , Host Microbial Interactions/genetics , Host Microbial Interactions/immunology , Humans , Immunity, Humoral/genetics , Plasma Cells/immunology , Polymorphism, Genetic , RNA Editing/genetics , RNA, Viral/genetics