Biology subjects

Jacolin, F.

Publications and source records attributed to Jacolin, F..

3 recordsLinked to original sources

bioRxiv2026

A rapid agarose-free protocol for preparing human organotypic lung cultures to study respiratory virus infection and evaluate antivirals ex vivo

We describe a standardized and reproducible procedure to generate human organotypic lung cultures from surgical lung resection for the study of respiratory infections. The protocol details tissue harvesting, biopsy punching, mechanical slicing, culture at the air-liquid interface. This technique enables robust ex vivo infections of human lung tissue with respiratory viruses, including Influenza A and Nipah. The described system can be used to study host-pathogen interactions, analyze innate immune responses, and evaluate antiviral candidates in physiologically relevant human lung tissue. For complete details on the use and execution of this protocol, please refer to Cezard et al1.

pathology↗

bioRxiv2025

NAD metabolism plays multiple roles in influenza A virus replication in a novel ex vivo model of mouse lung infection.

Despite the availability of prophylactic and therapeutic measures, Influenza A viruses (IAV) remain a major public health concern, causing an estimated 650 000 deaths annually. In this context, the identification of metabolic vulnerabilities of IAV replication could help develop complements to existing antiviral strategies. Here, we used nicotinamide phosphoribosyltransferase (NAMPT) inhibitors to demonstrate that nicotinamide adenine dinucleotide (NAD) is essential for IAV replication and infectious particles production both in vitro and ex vivo. We established an innovant ex vivo model of murine organotypic lung cultures (mOLC) that is pertinent to analyze cell metabolic alterations triggered by IAV infection. Using untargeted metabolomic profiling and spatial transcriptomic analyses, our research revealed that IAV-infection decreased NAD+ levels in mOLCs, while PARPs, a group of NAD+-consuming enzymes, were upregulated. Pharmacological inhibition of the mono-ADP-ribosyl-transferase (mono-ART) activity of PARPs restricted IAV infection ex vivo, suggesting that NAD+ sustains the proviral activity of these enzymes. Overall, our study identifies NAD metabolism as a central regulator of IAV infection, providing redox cofactor to host cell biosynthetic processes and substrate for mono-ART activity. Our results highlight NAMPT and PARP mono-ART activity as promising antiviral targets. Significance StatementViruses are intracellular parasites that rely on the host cellular metabolism for their replication. Our results demonstrate that Influenza A virus (IAV) replication is critically dependent on NAD availability, an enzyme cofactor essential for redox metabolic reactions and a substrate for NAD+-consuming enzymes. Using a novel ex vivo infection model of mouse lung tissue, we found that IAV infection results in NAD depletion and enhanced expression of NAD-consuming PARP enzymes. Inhibitors of NAD biosynthesis and mono(ADP-ribosyl) transferase activity of PARP are restricting viral replication and infectious particles production. These findings highlight the proviral role for PARP mono-ART activity and identify NAMPT and PARP inhibitors as potential host-directed antivirals against IAV.

microbiology↗

bioRxiv2025

Cis-aconitate therapy protects against influenza mortality by dual targeting of viral polymerase and ERK/AKT/NF-κB signaling

Influenza virus poses a significant global health challenge, causing approximately 500,000 deaths annually. Its ability to evade antiviral treatments and vaccine-induced immunity underscores the need for novel therapeutic approaches. Our study identifies cis-aconitate (cis-aco), a mitochondria-derived metabolite, as a potent dual-action agent against influenza, independently of its metabolic derivative, itaconate. Cis-aco impairs viral polymerase activity, suppressing viral mRNA expression and protein synthesis to inhibit replication across a range of influenza subtypes. This antiviral efficacy is confirmed in ex vivo human airway and lung organotypic models. Beyond its antiviral properties, cis-aco exhibits potent anti-inflammatory effects, disrupting key inflammatory cascades and reducing the secretion of inflammatory mediators. In a mouse model of influenza pneumonia, cis-aco mitigates viral replication, inflammation, and immune cell activation, significantly improving survival. Notably, its efficacy persists even when administered at later stages of infection, when oseltamivir/Tamiflu(R) is no longer effective. These findings position cis-aco as a promising influenza treatment, combining antiviral and anti-inflammatory benefits within a clinically relevant timeframe.

immunology↗