Biology subjects

Trouillet-Assant, S.

Publications and source records attributed to Trouillet-Assant, S..

7 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

Functional alterations of immune gene expression in ICU and non-ICU patients with Legionnaires' disease, a prospective observational study

Legionnaires disease (LD), a pneumonia caused by Legionella pneumophila intracellular bacterium, leads to intensive care unit (ICU) admission in 20-40% of cases. While these ICU-LD patients display severe lung injury or septic shock, their functional immune response remains poorly understood. The present study aimed, through a large immune gene expression assessment, to improve the understanding of immune cell functionality after whole blood LPS ex vivo stimulation in ICU-LD patients compared with non-ICU. Both ICU and non-ICU-LD displayed altered gene expression indicating that both patients immune cells are less able to respond to the LPS ex vivo stimulus than a healthy population. ICU-LD patients had 1.6-fold greater number of less-expressed genes (35/93 vs 22/93, p=0.039), and lower Log2(FC) of these genes (median [IQR]: -1.9 [-2.6;-1.5] vs -1.2 [-1.7;-0.9], p=0.0011) than non-ICU-LD. Seven genes were significantly less expressed by ICU-LD patients (IRF7, MX1, NFKBI2, NFKBIA, RELB, SRC, TIM3; p-value range: 0.029-0.0080). Top five gene ontology biological processes, subcellular localisations, and reactome pathways (STRING database) uniquely enriched in ICU-LD-patients and related less-expressed genes were cellular response to LPS (CCL2, NFKBIA, IRAK2, TIM3, SRC, NFKB1), regulation of IFN-{beta} production (IRF7, RIG1, OAS2, RELB), I-{kappa}B/NF-{kappa}B complex (NFKBIA, NFKB1, NFKB2), IFN regulatory factor complex (RIG1, IRF7), and TRAF6-mediated NF-{kappa}B activation pathway (NFKBIA, NFKB1, NFKB2, RIG1). Immune gene expression alterations in LD after LPS stimulation were found herein, with more pronounced alterations in ICU-LD patients. A reduced expression of key genes and pathways involved in controlling Legionella proliferation in ICU-LD patients may contribute to increased disease severity.

immunology↗

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

Immunological and clinical markers of post-acute sequelae of COVID-19: Insights from mild and severe cases six months post-infection

Post-acute sequelae of COVID-19 (PASC) is a complex and multifaceted clinical challenge requiring to emphasize its underlying pathophysiological mechanisms. This study assessed hundreds of virological, serological, immunological, and tissue damage biomarkers in two patient cohorts who experienced mild (n=270) or severe (n=188) COVID-19, 6 to 9 months post-initial infection, and in which 40% and 57.4% of patients, respectively, developed PASC. Blood analysis showed that mains differences observed in humoral, viral, and biological biomarkers were associated with the initial COVID-19 severity, rather than being specifically linked to PASC. However, patients with PASC displayed altered CD4+ and CD8+ memory T-cell subsets, with higher cytokine-secreting cells and increased terminally differentiated CD45RA+ effector memory T cells (TEMRA). Elevated SARS-CoV-2-specific T cells responsive to nucleocapsid/membrane proteins with a TEMRA phenotype were also observed. A random forest model identified these features and initial symptom duration as top variables discriminating PASC, achieving over 80% classification accuracy. HighlightsO_LINine months post-initial SARS-CoV-2 infection, over 40% of patients developed PASC C_LIO_LIRegardless of PASC, the initial disease form influenced the main immune differences C_LIO_LIPASC led to altered memory T-cell subsets with elevated TEMRA phenotype C_LIO_LIPASC presence is associated with disease form, initial symptom count and duration C_LI

immunology↗

bioRxiv2023

Staphylococcus aureus can use an alternative pathway to be internalized by osteoblasts in absence of β1 integrins

Staphylococcus aureus main internalization mechanism in osteoblasts relies on a tripartite interaction between bacterial fibronectin-binding proteins, extracellular matrix soluble fibronectin, and osteoblasts {beta}1 integrins. Caveolins, and particularly caveolin-1, have shown to limit the plasma membrane microdomain mobility, and consequently reduce the uptake of S. aureus in keratinocytes. In this study, we aimed to deepen our understanding of the molecular mechanisms underlying S. aureus internalization in osteoblasts. Mechanistically, S. aureus internalization requires endosomal recycling {beta}1 integrins as well as downstream effectors such as Src, Rac1, and PAK1. Surprisingly, in {beta}1 integrin deficient osteoblasts, S. aureus internalization is restored when Caveolin-1 is absent and requires v{beta}3/v{beta}5 integrins as backup fibronectin receptors. Altogether, our data support that {beta}1 integrins regulate the level of detergent-resistant membrane at the plasma membrane in a an endosomal and Caveolin-1 dependent manner. SUMMARY STATEMENTStaphylococcus aureus can be internalized by osteoblasts via a different mechanism than the main 5{beta}1/fibronectin/fibronectin-binding protein that likely involves v{beta}3 or v{beta}5 integrin.

cell biology↗

bioRxiv2020

Characterization and treatment of SARS-CoV-2 in nasal and bronchial human airway epithelia

In the current COVID-19 pandemic context, proposing and validating effective treatments represents a major challenge. However, the lack of biologically relevant pre-clinical experimental models of SARS-CoV-2 infection as a complement of classic cell lines represents a major barrier for scientific and medical progress. Here, we advantageously used human reconstituted airway epithelial models of nasal or bronchial origin to characterize viral infection kinetics, tissue-level remodeling of the cellular ultrastructure and transcriptional immune signatures induced by SARS-CoV-2. Our results underline the relevance of this model for the preclinical evaluation of antiviral candidates. Foremost, we provide evidence on the antiviral efficacy of remdesivir and the therapeutic potential of the remdesivir-diltiazem combination as a rapidly available option to respond to the current unmet medical need imposed by COVID-19. One Sentence SummaryNew insights on SARS-CoV-2 biology and drug combination therapies against COVID-19.

microbiology↗

bioRxiv2020

Molecular characterization of SARS-CoV-2 in the first COVID-19 cluster in France reveals an amino-acid deletion in nsp2 (Asp268Del)

We present the first genetic characterization of a COVID-19 cluster in Europe using metagenomic next-generation sequencing (mNGS). Despite low viral loads, the mNGS workflow used herein allowed to characterize the whole genome sequences of SARS-CoV2 isolated from an asymptomatic patient, in 2 clinical samples collected 1 day apart. Comparison of these sequences suggests viral evolution with development of quasispecies. In addition, the present workflow identified a new deletion in nsp2 (Asp268Del) which was found in all 3 samples originating from this cluster as well as in 37 other viruses collected in England and in Netherlands, suggesting the spread of this deletion in Europe. The impact of Asp268Del on SARS-CoV-2 transmission and pathogenicity, as well as on PCR performances and anti-viral strategy should be rapidly evaluated in further studies.

microbiology↗