Biology subjects

Bergeron, E.

Publications and source records attributed to Bergeron, E..

6 recordsLinked to original sources

bioRxiv2026

ISG15-USP18 signaling restrains viperin-dependent metabolic antiviral restriction

Type I interferon (IFN-I) responses are tightly regulated to balance antiviral defense with cellular homeostasis. In humans, interferon-stimulated gene 15 (ISG15) functions as a critical negative regulator of IFN-I signaling by stabilizing the IFN negative regulator USP18, yet the functional consequences of ISG15 deficiency remain elusive. Here, we show that the loss of ISG15 exaggerates the JAK-STAT activation and, downstream, amplifies multiple ISGs including the nucleotide-modifying enzyme RSAD2 (viperin). Our quantitative proteomics, genetic reconstitution, and signaling analyses establish that defective USP18 stabilization skews the IFN response towards viperin expression. This amplified ISG network promotes viperin-catalyzed accumulation of the antiviral nucleotide analog ddhCTP, resulting in enhanced inhibition of viral RNA synthesis and the replication of Crimean-Congo hemorrhagic fever virus and SARS-CoV-2. Together, these findings demonstrate an ISG15-USP18-viperin axis that can be targeted to boost the metabolic antiviral restriction.

microbiology↗

bioRxiv2026

Modular mRNA LNP design integrates RNA, lipid, and antigen engineering for protective vaccination

mRNA-lipid nanoparticle (LNP) vaccines are programmable, multi-component systems in which immune outcomes emerge from coupled control of nanoparticle chemistry, RNA regulatory architecture, and antigen design. Here we establish an integrated engineering framework that quantitatively maps how ionizable lipid identity, untranslated region (UTR) configuration, and 5' cap structure shape innate activation landscapes and thereby tune the magnitude, cellular distribution, and polarization of adaptive immunity. Benchmarking three ionizable lipids shows that lipid chemistry imprints distinct cytokine and chemokine milieus during dendritic cell-T cell priming that mirror downstream T cell activation phenotypes, identifying lipid structure as a determinant of pathway-selective activation; notably, our first-in-study lipid exhibits benchmark-comparable immunostimulatory profiles, supporting further translational evaluation. Using Crimean-Congo hemorrhagic fever virus (CCHFV) as a model high-consequence pathogen, we show that UTRs act as modular regulatory elements that redirect cytokine outputs, tuning effector versus proliferative programs and expanding helper polarization in an antigen-dependent manner. Cap structure functions primarily as a quantitative gain control, scaling cellular and humoral response magnitude without overriding antigen-defined polarization. Within this optimized platform, antigen architecture defines functional constraints on protection: structural modifications reshape immune hierarchies and antibody quality. Integrating these design axes yields an optimized mRNA-LNP vaccine encoding the CCHFV secreted glycoprotein complex (sGCs) that achieves 90% protection in an immunosuppressed murine lethal-challenge model with minimal clinical signs. Together, these data define generalizable design principles for rational, multi-parameter optimization of mRNA-LNP vaccines.

microbiology↗

bioRxiv2024

Behavioral and neural correlates of diverse conditioned fear responses in male and female rats

Pavlovian fear conditioning is a widely used tool that models associative learning in rodents. For decades the field has used predominantly male rodents and focused on a sole conditioned fear response: freezing. However, recent work from our lab and others has identified darting as a female-biased conditioned response, characterized by an escape-like movement across a fear conditioning chamber. It is also accompanied by a behavioral phenotype: Darters reliably show decreased freezing compared to Non-darters and males and reach higher velocities in response to the foot shock ("shock response"). However, the relationship between shock response and conditioned darting is not known. This study investigated if this link is due to differences in general processing of aversive stimuli between Darters, Non-darters and males. Across a variety of modalities, including corticosterone measures, the acoustic startle test, and sensitivity to thermal pain, Darters were found not to be more reactive or sensitive to aversive stimuli, and, in some cases, they appear less reactive to Non-darters and males. Analyses of cFos activity in regions involved in pain and fear processing following fear conditioning identified discrete patterns of expression among Darters, Non-darters, and males exposed to low and high intensity foot shocks. The results from these studies further our understanding of the differences between Darters, Non-darters and males and highlight the importance of studying individual differences in fear conditioning as indicators of fear state.

neuroscience↗

bioRxiv2022

Sounding the alarm: sex differences in rat ultrasonic vocalizations during Pavlovian fear conditioning and extinction

Pavlovian fear conditioning is a prevalent tool in the study of aversive learning, which is a key component of stress-related psychiatric disorders. Adult rats can exhibit various threat-related behaviors, including freezing, motor responses and ultrasonic vocalizations (USVs). While these responses can all signal aversion, we know little about how they relate to one another. Here we characterize USVs emitted by male and female rats during cued fear acquisition and extinction and assess the relationship between different threat-related behaviors. To probe the effects of aversive stimulus intensity, we exposed the rats to mild (0.3 mA), moderate (0.5 mA) or strong (1 mA) foot shocks. We found that males consistently emitted more alarm calls than females, and male alarm calls were more closely contingent on shock intensity than were female alarm calls. Furthermore, 25 % of males and 45 % of females did not emit alarm calls. Males that made alarm calls had significantly higher levels of freezing than males who did not, while no differences in freezing were observed between female alarm callers and non-callers. Alarm call emission was also affected by the predictability of the shock; when unpaired from a tone cue, both males and females started emitting alarm calls significantly later. Some rats continued to alarm-call during extinction learning (90% of males, 30% of females) and retrieval (65% of males, 20% of females). Collectively these data suggest sex-dependence in how behavioral readouts relate to innate and conditioned threat responses. Importantly, we suggest that the same behaviors can signal sex-dependent features of aversion. Significance statementBehavioral neuroscientists can access various outputs during behavioral tests to draw conclusions about internal states of animals. While freezing is the most common index of rodents feeling threatened, these animals also emit specific ultrasonic vocalizations during aversive situations. Here we record several motor and vocal behaviors to assess how they relate to each other as threat responses, and how such relationships vary across sex. We found robust differences in how much male and female rats engaged in so-called alarm vocalizations. These vocalizations were subject to extinction in both sexes, but correlated with freezing only in males. As the field advances to include more females in preclinical research, it is crucial that we understand how similar-appearing outputs may reflect sex-biased features.

animal behavior and cognition↗

bioRxiv2022

Efficient rescue of a newly classified Ebinur lake orthobunyavirus with GFP reporter and its application in rapid antiviral screening

Orthobunyaviruses have been reported to cause severe diseases in humans or animals, posing a threat to human health and social economy. Ebinur lake virus (EBIV) is a newly classified orthobunyavirus, which needs further intensive study and therapies to cope with its potential infection risk to human and animals. Here, through the reverse genetics system, the recombinant EBIV of wild type (rEBIV/WT) and NP-conjugated-eGFP (rEBIV/eGFP/S) were rescued for the application of the rapid antiviral drug screening. The eGFP fluorescence signal of the rEBIV/eGFP/S was stable in the process of successive passage in BHK-21 cells (over 10 passages) and this recombinant virus could replicate in various cell lines. Compared to the wild type EBIV, the rEBIV/eGFP/S caused the smaller plaques and its peak titers were lower, suggesting attenuation due to the eGFP insertion. Through the high-content screening (HCS) system, ribavirin showed an inhibitory effect on the rEBIV/eGFP/S with an EC50 of 21.91 M, while favipiravir did not inhibit, even at high concentrations. In addition, five of ninety-six natural compounds had antiviral against EBIV. The robust reverse genetics system for EBIV will facilitate investigation into replication and assembly mechanisms and assist drug and vaccine development.

molecular biology↗

bioRxiv2020

Rapid Development of Neutralizing and Diagnostic SARS-COV-2 Mouse Monoclonal Antibodies

The need for high-affinity, SARS-CoV-2-specific monoclonal antibodies (mAbs) is critical in the face of the global COVID-19 pandemic, as such reagents can have important diagnostic, research, and therapeutic applications. Of greatest interest is the ~300 amino acid receptor binding domain (RBD) within the S1 subunit of the spike protein because of its key interaction with the human angiotensin converting enzyme 2 (hACE2) receptor present on many cell types, especially lung epithelial cells. We report here the development and functional characterization of 29 nanomolar-affinity mouse SARS-CoV-2 mAbs created by an accelerated immunization and hybridoma screening process. Differing functions, including binding of diverse protein epitopes, viral neutralization, impact on RBD-hACE2 binding, and immunohistochemical staining of infected lung tissue, were correlated with variable gene usage and sequence.

immunology↗