In middle to late 2023, a sublineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron XBB, EG.5.1 (a progeny of XBB.1.9.2), is spreading rapidly around the world. We performed multiscale investigations, including phylogenetic analysis, epidemic dynamics modeling, infection experiments using pseudoviruses, clinical isolates, and recombinant viruses in cell cultures and experimental animals, and the use of human sera and antiviral compounds, to reveal the virological features of the newly emerging EG.5.1 variant. Our phylogenetic analysis and epidemic dynamics modeling suggested that two hallmark substitutions of EG.5.1, S:F456L and ORF9b:I5T are critical to its increased viral fitness. Experimental investigations on the growth kinetics, sensitivity to clinically available antivirals, fusogenicity, and pathogenicity of EG.5.1 suggested that the virological features of EG.5.1 are comparable to those of XBB.1.5. However, cryo-electron microscopy revealed structural differences between the spike proteins of EG.5.1 and XBB.1.5. We further assessed the impact of ORF9b:I5T on viral features, but it was almost negligible in our experimental setup. Our multiscale investigations provide knowledge for understanding the evolutionary traits of newly emerging pathogenic viruses, including EG.5.1, in the human population.

• MeSH
• Antiviral Agents pharmacology   MeSH
• Chlorocebus aethiops MeSH
• COVID-19 * virology   MeSH
• Cryoelectron Microscopy MeSH
• Phylogeny * MeSH
• Spike Glycoprotein, Coronavirus * genetics   chemistry   MeSH
• Humans MeSH
• Mice MeSH
• SARS-CoV-2 * genetics   MeSH
• Vero Cells MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

In late 2022, various Omicron subvariants emerged and cocirculated worldwide. These variants convergently acquired amino acid substitutions at critical residues in the spike protein, including residues R346, K444, L452, N460, and F486. Here, we characterize the convergent evolution of Omicron subvariants and the properties of one recent lineage of concern, BQ.1.1. Our phylogenetic analysis suggests that these five substitutions are recurrently acquired, particularly in younger Omicron lineages. Epidemic dynamics modelling suggests that the five substitutions increase viral fitness, and a large proportion of the fitness variation within Omicron lineages can be explained by these substitutions. Compared to BA.5, BQ.1.1 evades breakthrough BA.2 and BA.5 infection sera more efficiently, as demonstrated by neutralization assays. The pathogenicity of BQ.1.1 in hamsters is lower than that of BA.5. Our multiscale investigations illuminate the evolutionary rules governing the convergent evolution for known Omicron lineages as of 2022.

• MeSH
• Biological Assay MeSH
• COVID-19 * MeSH
• Phylogeny MeSH
• Cricetinae MeSH
• Antibodies, Neutralizing MeSH
• Antibodies, Viral MeSH
• SARS-CoV-2 genetics   MeSH
• Amino Acid Substitution MeSH
• Animals MeSH
• Check Tag
• Cricetinae MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

In late 2022, SARS-CoV-2 Omicron subvariants have become highly diversified, and XBB is spreading rapidly around the world. Our phylogenetic analyses suggested that XBB emerged through the recombination of two cocirculating BA.2 lineages, BJ.1 and BM.1.1.1 (a progeny of BA.2.75), during the summer of 2022. XBB.1 is the variant most profoundly resistant to BA.2/5 breakthrough infection sera to date and is more fusogenic than BA.2.75. The recombination breakpoint is located in the receptor-binding domain of spike, and each region of the recombinant spike confers immune evasion and increases fusogenicity. We further provide the structural basis for the interaction between XBB.1 spike and human ACE2. Finally, the intrinsic pathogenicity of XBB.1 in male hamsters is comparable to or even lower than that of BA.2.75. Our multiscale investigation provides evidence suggesting that XBB is the first observed SARS-CoV-2 variant to increase its fitness through recombination rather than substitutions.

• MeSH
• COVID-19 * MeSH
• Phylogeny MeSH
• Spike Glycoprotein, Coronavirus genetics   MeSH
• Cricetinae MeSH
• Humans MeSH
• Recombination, Genetic MeSH
• SARS-CoV-2 genetics   MeSH
• Animals MeSH
• Check Tag
• Cricetinae MeSH
• Humans MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Species attributes are commonly used to infer impacts of environmental change on multiyear species trends, e.g. decadal changes in population size. However, by themselves attributes are of limited value in global change attribution since they do not measure the changing environment. A broader foundation for attributing species responses to global change may be achieved by complementing an attributes-based approach by one estimating the relationship between repeated measures of organismal and environmental changes over short time scales. To assess the benefit of this multiscale perspective, we investigate the recent impact of multiple environmental changes on European farmland birds, here focusing on climate change and land use change. We analyze more than 800 time series from 18 countries spanning the past two decades. Analysis of long-term population growth rates documents simultaneous responses that can be attributed to both climate change and land-use change, including long-term increases in populations of hot-dwelling species and declines in long-distance migrants and farmland specialists. In contrast, analysis of annual growth rates yield novel insights into the potential mechanisms driving long-term climate induced change. In particular, we find that birds are affected by winter, spring, and summer conditions depending on the distinct breeding phenology that corresponds to their migratory strategy. Birds in general benefit from higher temperatures or higher primary productivity early on or in the peak of the breeding season with the largest effect sizes observed in cooler parts of species' climatic ranges. Our results document the potential of combining time scales and integrating both species attributes and environmental variables for global change attribution. We suggest such an approach will be of general use when high-resolution time series are available in large-scale biodiversity surveys.

• MeSH
• Biodiversity * MeSH
• Diet MeSH
• Population Density MeSH
• Climate Change * MeSH
• Animal Migration MeSH
• Birds * MeSH
• Seasons MeSH
• Reproduction MeSH
• Models, Theoretical * MeSH
• Agriculture MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Europe MeSH

BACKGROUND: The extent to which ambient benzo[a]pyrene (B[a]P) contributes to mechanistically distinct de novo asthma remains unknown. OBJECTIVES: To identify molecular signatures and regulatory networks underlying childhood exposure to ambient B[a]P and asthma, using robust and unbiased systems biology approaches. METHODS: Clinically confirmed asthmatic (n = 191) vs. control (n = 194) children (aged, 7-15) were enrolled from a polluted urban center and semi-rural region in Czech Republic. Contemporaneous B[a]P concentration, gene expressions, DNA methylation data were analyzed against asthma diagnosis, as well as a modified prognostic index of asthma, using integrative multiscale co-expression network analysis. Sample-wise cell type compositions were inferred by a machine learning approach (i.e. CIBERSORT) with reference gene expressions of purified 38 distinct hematopoietic cell states from umbilical cord (i.e. stem cell/progenitors) or peripheral blood (i.e. lymphocytes). RESULTS: The median outdoor B[a]P was increased near the homes of the urban children with 'moderate' or 'severe' prognostic markers of asthma, but not in the urban controls. An elevated B[a]P induced epigenetic suppression of NF-κB inflammation, decreased Natural Killer T (NKT) cells and activated anti-inflammatory IL10-secreting CD8+ T effective memory cells. B[a]P was positively correlated with an increased expression of a heme biosynthesis gene, ALAS2, which in turn, appears to promote concurrent increase of neutrophilic metamyelocyte and mature CD71low erythroid cells. Furthermore, erythroid-specific master transcription regulator gene (GATA1), glutathione transferase genes (GSTM1 and GSTM3) and Eosinophil marker (IL5RA) were simultaneously activated in the urban asthma cases. CONCLUSIONS: B[a]P might contribute to concurrent suppression of pro-inflammatory (e.g. NF-κB mediated NKT cells), and activation of anti-inflammatory pathways (e.g. IL10-secreting CD8+ T cells) in the urban asthmatic children. In addition, B[a]P appears to elevate heme biosynthesis, which in turn, promotes neutrophilic metamyelocyte expansion and reduction of CD71+ erythroids.

• MeSH
• Benzo(a)pyrene toxicity   MeSH
• Biomarkers blood   MeSH
• Asthma * chemically induced   MeSH
• Child MeSH
• Hematopoiesis drug effects   MeSH
• Humans MeSH
• Adolescent MeSH
• Rural Population MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH