Biology subjects

Wileveau, A.

Publications and source records attributed to Wileveau, A..

3 recordsLinked to original sources

bioRxiv2026

Temperature-Dependent Replication and Sensitivity to Innate Immunity of Human Coronavirus HKU1

The human coronavirus HKU1, causing common colds and occasionally severe illness, remains largely uncharacterized because it has not been successfully grown on immortalized cells. Here, we identified Caco2 cells overexpressing TMPRSS2, the HKU1 receptor, as being highly permissive to infection. HKU1 replicated efficiently, formed syncytia and released infectious progeny in these cells at 33{degrees}C, the temperature of the nasal cavity, but was attenuated at 37{degrees}C. Viral entry occurred similarly at both temperatures, but subsequent viral RNA synthesis was enhanced at 33{degrees}C. Released virions displayed higher stability at 33{degrees}C. In Caco2 and primary epithelial nasal cells, HKU1 was sensitive to interferons (IFN), but induction of IFN stimulated genes, such as IFN-Induced Transmembrane Proteins (IFITMs), was delayed at 33{degrees}C. Once expressed, IFITMs comparably inhibited HKU1 fusion at both temperatures. In contrast, SARS-CoV-2 robustly replicated at 37{degrees}C. Thus, cellular permissiveness, innate immunity and viral properties collectively explain why HKU1 replicates more efficiently at nasal temperature. Our results highlight temperature-sensitivity disparities between coronaviruses, likely associated to different pathogenic outcomes.

microbiology↗

bioRxiv2026

TMPRSS2 reduces antibody recognition of SARS-CoV-2 spike

The serine protease TMPRSS2 acts as a cofactor for SARS-CoV-2 entry by cleaving the viral spike (S) to initiate fusion. Whether TMPRSS2 has an impact on humoral immune response against S remains poorly characterized. Here, we show that TMPRSS2 impairs antibody binding to S. In S-expressing and infected cells, TMPRSS2 decreases monoclonal antibody (mAb) and immune serum binding, as well as antibody-dependent cellular cytotoxicity (ADCC) induction. Using a panel of 39 mAbs targeting various S regions, we observe that those binding to the S2 subunit are the most affected by TMPRSS2. TMPRSS2 promotes a partial shedding of S1 and changes S2 conformation. This processing reduces Angiotensin-Converting Enzyme 2 (ACE2) binding while increasing cell-cell fusion. We further observe that the capacity of TMPRSS2 to decrease antibody recognition is conserved across coronaviruses and shared with other TMPRSS proteins. However, TMPRSS2 expression in infected cells does not impact significantly virions infectivity or the antibody recognition, as measured by flow virometry. Collectively, our findings suggest that TMPRSS2 processing of S favors a fusion intermediate conformation which is less sensitive to antibody recognition.

immunology↗

bioRxiv2025

An image-based CRISPR screen reveals splicing-mediated control of HP1α condensates

Heterochromatin Protein 1 (HP1) is a fundamental component of constitutive heterochromatin, forming subnuclear condensates whose regulation and function remain poorly understood. Here, we present an image-based CRISPR screen targeting nuclear factors that identifies splicing as a pivotal pathway regulating HP1 condensates. We discovered that unspliced intronic RNA modulates HP1 condensates by interacting co-transcriptionally with HP1. By modulating the intron content, RNA processing restricts HP1-RNA interactions at chromatin, thus enabling heterochromatin organization. Disruption of HP1 condensates due to enhanced interactions with unspliced RNA leads to loss of heterochromatin and the activation of stress response protective genes. We propose that RNA is a central component of heterochromatin that modulates HP1 condensates, and that RNA processing enzymes act as a surveillance mechanism for condensates by dynamically regulating the network of multi-valent interactions between RNA and chromatin factors. This model underscores the crosstalk between chromatin organization, transcription, and RNA processing, potentially governing broader nuclear functions.

genetics↗