Biology subjects

Boudreault, S.

Publications and source records attributed to Boudreault, S..

3 recordsLinked to original sources

bioRxiv2026

Mapping global transcript isoform landscapes of influenza A virus infection and interferon stimulation reveals RNA-binding protein networks associated with immune remodeling

Infected cells rapidly adapt their transcriptional profile to upregulate genes that limit pathogen replication and promote inflammation. Viruses also induce widespread changes in host gene expression, and both host and virus further remodel the transcriptome through targeted mRNA degradation, modulation of alternative splicing, and alterations at transcript 5 and 3 prime ends. The complexity of the response to infection makes it difficult to understand which transcriptional changes are driven by the virus and which reflect the host antiviral program. Short-read RNA sequencing has been the primary tool for studying these changes, but its inability to resolve full-length transcript isoforms limits isoform switching-based analyses, narrowing our understanding of how transcript usage shapes immunity. Here we profiled the host transcriptome in response to interferon-{beta} treatment or influenza A virus infection using both short- and long-read RNA sequencing analyzed with the SQANTI3 pipeline. Because isoform switching and transcript abundance change are distinct regulatory events, we focused our analysis on differential transcript usage to uncover a layer of transcriptome remodeling that standard expression analysis cannot detect. Pathway analysis revealed distinct regulons for genes undergoing transcriptional upregulation compared with those undergoing isoform switching. These data provide a rich resource for querying the isoform changes underlying shared and distinct transcriptional programs triggered by viral infection or innate immune stimulation. To identify putative mechanisms coordinating these stimulation-dependent isoform changes, we integrated 232 eCLIP datasets and found a small set of RNA-binding proteins localized at these isoform switches, including DDX3X. Comparing the responses to interferon and to virus highlighted RNA-binding proteins associated with infection-dependent immune remodeling. Altogether, these results demonstrate the value of hybrid sequencing for deciphering the post-transcriptional regulatory code active during the antiviral response.

immunology↗

bioRxiv2025

Nonsense-mediated decay controls a negative feedback loop in innate immune sensing

Nonsense-mediated decay (NMD) is an mRNA decay pathway which degrades potential harmful transcripts that contain premature termination codons. However, NMDs importance also extends to the control of isoform abundance under physiological conditions. During viral infection, NMD is inhibited through numerous mechanisms; however, NMD has been shown to have both antiviral as well as proviral activities, raising further questions into the role and control of NMD during viral infection. These observations have led us to investigate the potential involvement of NMD in dsRNA sensing as a mechanism that might explain these discrepancies. Using EIF4A2 exon 10B inclusion as an example of AS-NMD isoform accumulating during viral infection, we show that dsRNA sensing inhibits NMD. This effect is correlated with translational blockade and is driven primarily by RNaseL activation, and by PKR in the absence of RNaseL activation. Surprisingly, NMD inhibition limits the induction of IFN-{beta} as well as interferon-stimulated genes, and this effect is upstream of IRF3 phosphorylation and translocation to the nucleus. NMD inhibition also decreases PKR and RNaseL activation as well as PIC-mediated cell death by decreasing the dsRNA content, suggesting NMD directly controls dsRNA sensing by controlling the dsRNA load. Therefore, inhibition of NMD upon dsRNA sensing provides a negative feedback loop that contributes to shaping the innate immune sensing pathways. SIGNIFICANCENonsense-mediated decay (NMD) is a translation-dependent mRNA decay pathway that plays an important role in shaping the transcriptome. In this manuscript, we show that dsRNA sensing, as is typical during viral infection, inhibits NMD mainly through the translational inhibition caused by RNaseL activation. This NMD inhibition forms a negative-feedback loop that limits dsRNA sensing, thus preventing overactivation of dsRNA-mediated pathways. These findings contribute to a better understanding of the molecular mechanisms that limit antiviral responses as well as inflammation and inform the critical role that mRNA processes plays in innate immunity.

immunology↗

bioRxiv2022

Cellulosic copper nanoparticles and a hydrogen peroxide-based disinfectant protect Vero E6 cells against infection by viral pseudotyped particles expressing SARS-CoV-2, SARS-CoV or MERS-CoV Spike protein.

Severe acute respiratory syndrome (SARS) is a viral respiratory infection caused by human coronaviruses (HuCoV) that include SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV). Although their primary mode of transmission is through contaminated respiratory droplets from infected carriers, the deposition of expelled virus particles onto surface and fomites could contribute to viral transmission. Here, we use replication-deficient murine leukemia virus (MLV) pseudoviral particles expressing SARS-CoV-2, SARS-CoV, or MERS-CoV Spike (S) protein on their surface. These surrogates of native coronavirus counterparts serve as a model to analyze the S-mediated entry into target cells. Carboxymethyl cellulose (CMC) nanofibers that are combined with copper (Cu) exhibit strong antimicrobial properties. S-pseudovirions that are exposed to CMC-Cu nanoparticles (30 s) display a dramatic reduction in their ability to infect target Vero E6 cells, with [~]97% less infectivity as compared to untreated pseudovirions. In contrast, addition of the Cu chelator tetrathiomolybdate protects S- pseudovirions from CMC-Cu-mediated inactivation. When S-pseudovirions were treated with a hydrogen peroxide-based disinfectant (denoted SaberTM) used at 1:16 dilution, their infectivity was dramatically reduced by [~]98%. However, the combined use of SaberTM and CMC-Cu is the most effective approach to restrict infectivity of SARS-CoV-2-S, SARS-CoV-S, and MERS-CoV-S pseudovirions in Vero E6 cell assays. Together, these results show that cellulosic Cu nanoparticles enhance the effectiveness of diluted SaberTM sanitizer, setting up an improved strategy to lower the risk of surface- and fomite-mediated transmission of enveloped respiratory viruses.

microbiology↗