Biology subjects

Herve, S.

Publications and source records attributed to Herve, S..

4 recordsLinked to original sources

bioRxiv2026

Genetic diversity and phylogeography of swine influenza A virus in 2013-2022 in Europe using a harmonized genotyping nomenclature

Swine Influenza A virus (swIAV) poses constant health threat for both humans and animals. This study comprehensively analysed the genetic diversity and evolution of European swIAVs from 2013 to 2022. To address existing classification gaps, an easily accessible full-genome genotyping tool based on Nextclade was developed alongside a global nomenclature system. Application of this tool to European sequence data revealed unprecedented genetic diversity, successfully identifying 150 swIAV genotypes mixing segments of both swine and human origin. Bayesian phylogeographic models, combined with economic data, identified that the trade of live weaner pigs for fattening drove the transboundary spread of swIAVs across Europe. The study detected repeated human-to-swine reverse-zoonotic events across multiple European countries. These findings clearly highlight the role of commercial pig movements in viral dissemination and emphasize the critical importance of harmonized genomic surveillance to monitor swIAV viral evolution to inform global pre-pandemic preparedness strategies.

microbiology↗

bioRxiv2025

Colorectal cancer heterogeneity co-evolves with tumor architecture to determine disease outcome

Intratumoral heterogeneity, originating from genetic, epigenetic, and phenotypic cellular diversity, is pervasive in cancer. As these heterogeneous states employ diverse mechanisms to promote tumor progression, metastasis, and therapy resistance, emergence of cancer heterogeneity is one of the most significant barriers to curative treatment. Here we leverage deep learning approaches to develop a high-throughput image-analysis paradigm with subcellular resolution that quantifies and predicts colorectal cancer (CRC) patient outcome based on tissue architecture and nuclear morphology. We further combine this approach with spatial transcriptomics, multiplex immunohistochemistry, and patient-derived organoids to uncover a dynamic, co-evolutionary relationship between tumor architecture and cell states. We identify clinically relevant architectural interfaces in CRC tissue that diversify cellular identities by favoring distinct cancer stem cell states and thus promote evolution of tumor heterogeneity. Specifically, tissue fragmentation and associated compressive forces promote loss of classic stem cell signature and acquisition of fetal/regenerative stem cell states, which initially emerges as a hybrid state with features of epithelial-to-mesenchyme (EMT) transition. Additional tumor stroma communication then diversifies these states into distinct stem cell and EMT states at the invasive margins of tumors. Reciprocally, Wnt signaling state of tumor cells tunes their responsiveness to tissue architecture. Collectively, this work uncovers a feedback loop between cell states and tissue architecture that drives cancer heterogeneity and cell state diversification. Machine learning-based analyses harness this co-dependency, independently of mutational status or cancer stage, to predict patient outcome.

cancer biology↗

bioRxiv2024

Major change in swine influenza virus diversity in France owing to emergence and widespread dissemination of a newly introduced H1N2 1C genotype in 2020

Swine influenza A viruses (swIAV) are a major cause of respiratory disease in pigs worldwide, presenting significant economic and health risks. These viruses can reassort, creating new strains with varying pathogenicity and cross-species transmissibility. This study aimed to monitor the genetic and antigenic evolution of swIAV in France from 2019 to 2022. Molecular subtyping revealed a marked increase in H1avN2 cases from 2020 onwards, altering the previously stable subtypes distribution. Whole-genome sequencing and phylogenetic analyses of H1av (1C) strains identified ten circulating genotypes, including five new genotypes, marked by a significant predominance of the H1avN2#E genotype. It was characterized by an HA-1C.2.4, an N2-Gent/84, and internal protein-encoding genes belonging to a newly defined genogroup within the Eurasian avian-like (EA) lineage, the EA-DK subclade. H1avN2#E emerged in Brittany, the countrys most pig-dense region, and rapidly became the most frequently detected swIAV genotype across France. This drastic change in the swIAV lineages proportions at a national scale was unprecedented, making H1avN2#E a unique case for understanding swIAV evolution and spreading patterns. Phylogenetic analyses suggested an introduction of the H1avN2#E genotype from a restricted source, likely originating from Denmark. It spread rapidly with low genetic diversity at the start of the epizootic in 2020, showing increasing diversification in 2021 and 2022, and exhibiting reassortments with other enzootic genotypes. Amino acid sequence alignments of H1avN2#E antigenic sites revealed major mutations and deletions compared to vaccine 1C strain (HA-1C.2.2) and previously predominant H1avN1 strains (HA-1C.2.1). Antigenic cartography confirmed significant antigenic distances between H1avN2#E and other 1C strains, suggesting the new genotype escaped from the swine population preexisting immunity. Epidemiologically, the H1avN2#E virus exhibited epizootic hallmarks with more severe clinical outcomes compared to H1avN1 viruses. These factors likely contributed to the spread of H1avN2#E within the pig population. The rapid rise of H1avN2#E highlighted the dynamic nature of swIAV genetic and antigenic diversity, underscoring the importance of adapted surveillance programs to support risk assessment in the event of new outbreaks. This also demonstrate the need to strengthen biosecurity measures when receiving pigs in a herd and to limit trading of swIAV-excreting live swine between European countries.

evolutionary biology↗

bioRxiv2020

CENP-A chromatin prevents replication stress at centromeres to avoid structural aneuploidy

Chromosome segregation relies on centromeres, yet their repetitive DNA is often prone to aberrant rearrangements under pathological conditions. Factors that maintain centromere integrity to prevent centromere-associated chromosome translocations are unknown. Here, we demonstrate the importance of the centromere-specific histone H3 variant CENP-A in safeguarding DNA replication of alpha-satellite repeats to prevent structural aneuploidy. Rapid removal of CENP-A in S-phase, but not other cell cycle stages, caused accumulation of R-loops with increased centromeric transcripts, and interfered with replication fork progression. Replication without CENP-A causes recombination at alpha-satellites in an R-loop-dependent manner, unfinished replication and anaphase bridges. In turn, chromosome breakage and translocations arise specifically at centromeric regions. Our findings provide insights into how specialized centromeric chromatin maintains the integrity of transcribed noncoding repetitive DNA during S-phase. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=177 SRC="FIGDIR/small/277103v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@4e6dc4org.highwire.dtl.DTLVardef@1089c90org.highwire.dtl.DTLVardef@5ee5c2org.highwire.dtl.DTLVardef@3e300d_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗