Dataset Information

Peptidome Surveillance Across Evolving SARS-CoV-2 Lineages Reveals HLA Binding Conservation in Nucleocapsid Among Variants With Most Potential for T-Cell Epitope Loss in Spike.

ABSTRACT: To provide a unique global view of the relative potential for evasion of CD8+ and CD4+ T cells by SARS-CoV-2 lineages as they evolve over time, we performed a comprehensive analysis of predicted HLA-I and HLA-II binding peptides in Spike (S) and Nucleocapsid (N) protein sequences of all available SARS-CoV-2 genomes as provided by NIH NCBI at a bi-monthly interval between March and December of 2021. A data supplement of all B.1.1.529 (Omicron) genomes from GISAID in early December was also used to capture the rapidly spreading variant. A key finding is that throughout continued viral evolution and increasing rates of mutations occurring at T-cell epitope hotspots, protein instances with worst-case binding loss did not become the most frequent for any Variant of Concern (VOC) or Variant of Interest (VOI) lineage; suggesting T-cell evasion is not likely to be a dominant evolutionary pressure on SARS-CoV-2. We also determined that throughout the course of the pandemic in 2021, there remained a relatively steady ratio of viral variants that exhibit conservation of epitopes in the N protein, despite significant potential for epitope loss in S relative to other lineages. We further localized conserved regions in N with high epitope yield potential, and illustrated heterogeneity in HLA-I binding across the S protein consistent with empirical observations. Although Omicron's high volume of mutations caused it to exhibit more epitope loss potential than most frequently observed versions of proteins in almost all other VOCs, epitope candidates across its most frequent N proteins were still largely conserved. This analysis adds to the body of evidence suggesting that N may have merit as an additional antigen to elicit immune responses to vaccination with increased potential to provide sustained protection against COVID-19 disease in the face of emerging variants.

SUBMITTER: Wnuk K

PROVIDER: S-EPMC9260595 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Genome analyses have documented that there are differences in gene repertoire between evolutionary distant lineages of the same bacterial species; however, less is known about microevolutionary dynamics of gene loss and acquisition within bacterial lineages as they evolve over years. Here, we analyzed the genomes of 45 Pseudomonas aeruginosa lineages evolving in the lungs of cystic fibrosis (CF) patients to identify genes that are lost or acquired during the first years of infection. On average, lineage genome content changed by 88 genes (range, 0 to 473). Genes were more often lost than acquired, and prophage genes were more variable than bacterial genes. We identified convergent loss or acquisition of the same genes across lineages, suggesting selection for loss and acquisition of certain genes in the host environment. We found that a notable proportion of such genes are associated with virulence; a trait previously shown to be important for adaptation. Furthermore, we also compared the genomes across lineages to show that the within-lineage variable genes (i.e., genes that had been lost or acquired during the infection) often belonged to genomic content not shared across all lineages. In sum, our analysis adds to the knowledge on the pace and drivers of gene loss and acquisition in bacteria evolving over years in a human host environment and provides a basis to further understand how gene loss and acquisition play roles in lineage differentiation and host adaptation.IMPORTANCE Bacterial airway infections, predominantly caused by P. aeruginosa, are a major cause of mortality and morbidity of CF patients. While short insertions and deletions as well as point mutations occurring during infection are well studied, there is a lack of understanding of how gene loss and acquisition play roles in bacterial adaptation to the human airways. Here, we investigated P. aeruginosa within-host evolution with regard to gene loss and acquisition. We show that during long-term infection P. aeruginosa genomes tend to lose genes, in particular, genes related to virulence. This adaptive strategy allows reduction of the genome size and evasion of the host's immune response. This knowledge is crucial to understand the basic mutational steps that, on the timescale of years, diversify lineages and adds to the identification of bacterial genetic determinants that have implications for CF disease.

Dataset Information

Peptidome Surveillance Across Evolving SARS-CoV-2 Lineages Reveals HLA Binding Conservation in Nucleocapsid Among Variants With Most Potential for T-Cell Epitope Loss in Spike.

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