Biology subjects

Labadie, T.

Publications and source records attributed to Labadie, T..

3 recordsLinked to original sources

bioRxiv2026

The RLR-MAVS-IRF3 axis activates the IFN pathway to restrict Tonate virus (TONV) infection

Tonate virus (TONV) is a neglected mosquito-borne alphavirus of the Venezuelan equine encephalitis complex associated with febrile illness, encephalitis, and fetal central nervous system abnormalities. Yet, host pathways that sense TONV infection and restrict its replication remain poorly defined. Here, we investigated the interaction between TONV and the type I interferon (IFN-I) system in human cells. We show that TONV infection led to the accumulation of cytosolic double-stranded RNA and a robust IFN response. RIG-I and MDA5 depletion as well as that of MAVS and IRF3 strongly reduced TONV-induced IFN response. Disruption of RIG-I, MDA5, MAVS, or IRF3 resulted in an increase of dsRNA-positive cells and a higher viral RNA accumulation. Finally, we found that treatment with exogenous IFN-I strongly inhibits TONV replication reducing both viral RNA loads and infectious particle production. Thus, together, our results identify the RIG-I/MDA5-MAVS-IRF3 axis as a major pathway sensing TONV infection and establishing an IFN-I-dependent antiviral state, providing the first molecular characterization of TONV innate immune sensing in human cells.

immunology↗

bioRxiv2024

Selective manipulation of the host RNA-polymerase transcription fidelity increases phenotypic mutations in an insect Parvovirus

In the dynamic dance of evolution, organisms are often faced with fluctuating environments to which adaptation through selection of traditional heritable genetic mutations can be limiting. In this study, we unveil a refined mechanism of non-heritable variability in a virus with a compact DNA genome. We discovered that the genome of the Junona cnia densovirus (JcDV) experiences a 10-fold lower transcription fidelity than the rest of the hosts transcriptome, despite the shared transcription machinery. We found that the virus capsid proteins interact with the hosts RNA Polymerase II, and further show that truncating these proteins through early stop codons largely restore the transcriptional fidelity of viral genes. These observations suggest a potential mechanism for the selective manipulation of transcription accuracy. We also pinpoint specific sequence contexts that may provide other knobs to finely control the local transcription fidelity. We estimate that this lower transcriptional fidelity results in more than 7% of the viral proteome bearing at least one non-synonymous mutation. The production of non-heritable functional diversity by hijacking the transcriptional machinery might be a refined strategy to enhance short term adaptation within the complex and ever-changing host-parasite interface, and might be shared by other genetic parasites. Our findings shed light on a virus-specific transcription fidelity control mechanism, expanding our understanding of adaptive strategies in biological entities.

microbiology↗

bioRxiv2018

Influenza A virus environmental persistence is driven by the hemagglutinin and the neuraminidase

The transmission routes of Influenza A viruses (IAVs) submit virus particles to a wide range of environmental conditions that affect their transmission. In water, temperature, salinity and pH are important factors modulating viral persistence in a strain-dependant manner, and the viral factors driving IAV persistence remained to be described. We used an innovative method based on a real-time cell system analysis to quantify viral decay in an environmental model. Thus, we identified the viral hemagglutinin (HA) and neuraminidase (NA) as the main proteins driving the environmental persistence by comparing the inactivation slopes of several reassortant viruses. We also introduced synonymous and non-synonymous mutations in the HA or in the NA that modulated IAV persistence. Our results demonstrate that HA stability and expression level, as well as calcium-binding sites of the NA protein are molecular determinants of viral persistence.\n\nFinally, IAV particles could not trigger membrane fusion after environmental exposure, stressing the importance of the HA and the NA for environmental persistence.

microbiology↗