Biology subjects

Volmer, R.

Publications and source records attributed to Volmer, R..

7 recordsLinked to original sources

bioRxiv2026

Mechanism-based prediction of insertion-driven high pathogenicity avian influenza virus emergence

High pathogenicity avian influenza viruses (HPAIVs) emerge from H5 and H7 low-pathogenicity avian influenza virus progenitors through mutations that introduce a multibasic cleavage site in haemagglutinin. Although nucleotide insertions recurrently generate this motif, the molecular determinants of insertion and whether particular HA sequences are genetically predisposed to evolve toward HPAIV remain unknown. Combining experimental virology and thermodynamic modelling, we show that insertions arise through polymerase slippage controlled by local product-template duplex thermodynamics within the viral polymerase catalytic site. Predicted RNA secondary structures outside the polymerase are not required for high-frequency insertions and only modestly modulate insertion rates. We formalize this mechanism in HPAIVpredict, which predicts insertion profiles, recapitulates intermediates associated with documented HPAIV emergence events and identifies H5 and H7 sequence backgrounds predisposed to acquire functional multibasic cleavage sites.

microbiology↗

bioRxiv2026

RNA length and receptor usage define innate immune recognition across species.

Recognition of viral double-stranded RNA (dsRNA) is a central trigger of innate antiviral immunity, yet the role of RNA length in shaping immune sensing across species remains poorly defined. Here, we identify RNA length as a key determinant of innate immune activation and demonstrate that this parameter is differentially tuned across vertebrate hosts. Using defined dsRNA molecules, we compared immune responses in human, duck, and chicken cells. Short 5-triphosphorylated dsRNAs, including influenza-derived mini viral RNAs, robustly activated antiviral responses in human and duck cells but failed to do so in chicken cells. In contrast, longer dsRNAs induced immune activation across all species, revealing a species-specific threshold for dsRNA recognition. Mechanistically, this threshold is defined by differential engagement of RNA sensors. In human cells, sensing of short and intermediate dsRNA is strictly dependent on RIG-I, whereas in chicken cells, which lack RIG-I, MDA5 mediates dsRNA recognition and imposes a higher length requirement for activation. Consistent with this, duck cells, which retain RIG-I, respond to short dsRNA similarly to human cells. These differences in dsRNA sensing are accompanied by differential activation of downstream antiviral pathways, including PKR-dependent translational control and OAS/RNase L activation. Together, our findings identify RNA length as a fundamental parameter governing innate immune recognition and reveal that species-specific usage of RNA sensors constrains antiviral sensing, with implications for host susceptibility and virus-host interactions. Significance StatementRecognition of viral RNA is central to antiviral immunity, yet the rules governing which viral RNAs are sensed across species remain poorly understood. Here, we show that RNA length defines a species-specific threshold for innate immune recognition. Human and duck cells efficiently detect short viral double-stranded RNAs generated during influenza infection, whereas chicken cells respond only to substantially longer RNA duplexes. Mechanistically, this difference reflects the usage of distinct antiviral RNA sensors: RIG-I enables sensing of short viral RNAs, while MDA5 imposes a higher length requirement for activation. Our findings reveal that host species differ in the spectrum of viral RNA ligands accessible to immune detection, providing a framework for understanding species-specific antiviral responses and host susceptibility.

microbiology↗

bioRxiv2025

Use of ANCHOR viruses to validate radiative, physical and chemical decontamination systems in operational conditions.

ANCHOR tagged viruses provide a high-performance platform for the rapid evaluation of disinfection methods across chemical, radiative, and physical modalities. This study highlights the robustness of Vaccinia virus (VACV) and human Adenovirus type 5 (hAdV5) as environmental persistence models, demonstrating their suitability for testing disinfection protocols. ANCHOR imaging capability allows real-time visualization of disinfection efficacy, enabling rapid calibration and cost-effective validation of new disinfection systems. This technology provides essential support for the development and optimization of disinfection solutions in public areas up to the improvement of safety protocols in high-containment laboratories. The increasing number of BSL-4 laboratories worldwide underscores the critical needs for efficient and reliable decontamination systems and methods to test them in operational conditions to ensure biohazard safety. HighlightsO_LIANCHOR-tagged viruses provide a rapid and cost-effective platform for evaluating disinfection methods across chemical, physical, and radiative modalities. C_LIO_LIHuman Adenovirus type 5 (hAdV5) and Vaccinia virus (VACV) serve as robust environmental persistence models for testing viral decontamination protocols. C_LIO_LIThe use of ANCHOR viruses enables rapid real-time visualization of disinfection efficacy, improving safety validation in high-containment laboratories and public health applications. C_LI

microbiology↗

bioRxiv2021

The strength of the innate immune response drives the within-host competition between highly and low pathogenic avian influenza viruses

Highly pathogenic avian influenza viruses (HPAIV) emerge from low pathogenic avian influenza viruses (LPAIV) through the introduction of basic amino acids at the hemagglutinin (HA) cleavage site. Following viral evolution, the newly formed HPAIV likely represents a minority variant within the index host, predominantly infected with the LPAIV precursor. Using reverse-genetics engineered H5N8 viruses differing solely at the HA cleavage, we tested the hypothesis that the interaction between the minority HPAIV and the majority LPAIV could modulate the risk of HPAIV emergence and that the nature of the interaction could depend on the host species. In chickens, we observed that the H5N8LP increased H5N8HP replication and pathogenesis. By contrast, the H5N8LP antagonized H5N8HP replication and pathogenesis in ducks. Ducks mounted a more potent antiviral innate immune response than chickens against the H5N8LP, which correlated with H5N8HP inhibition. These data provide experimental evidence that HPAIV may be more likely to emerge in chickens than in ducks and underscore the importance of within-host viral variants interactions in viral evolution.

microbiology↗

bioRxiv2021

Intranasal type I interferon treatment is beneficial only when administered before clinical signs onset in the SARS-CoV-2 hamster model

Impaired type I interferons (IFNs) production or signaling have been associated with severe COVID-19, further promoting the evaluation of recombinant type I IFNs as therapeutics against SARS-CoV-2 infection. In the Syrian hamster model, we show that intranasal administration of IFN- starting one day pre-infection or one day post-infection limited weight loss and decreased viral lung titers. By contrast, intranasal administration of IFN- starting at the onset of symptoms three days post-infection had no impact on the clinical course of SARS-CoV-2 infection. Our results provide evidence that early type I IFN treatments are beneficial, while late interventions are ineffective, although not associated with signs of enhanced disease. One Sentence SummaryThe timing of type I interferon treatment is a critical determinant of its efficacy against SARS-CoV-2 infection.

microbiology↗

bioRxiv2020

Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters

Anosmia is one of the most prevalent symptoms of SARS-CoV-2 infection during the COVID-19 pandemic. However, the cellular mechanism behind the sudden loss of smell has not yet been investigated. The initial step of odour detection takes place in the pseudostratified olfactory epithelium (OE) mainly composed of olfactory sensory neurons surrounded by supporting cells known as sustentacular cells. The olfactory neurons project their axons to the olfactory bulb in the central nervous system offering a potential pathway for pathogens to enter the central nervous system by bypassing the blood brain barrier. In the present study, we explored the impact of SARS-COV-2 infection on the olfactory system in golden Syrian hamsters. We observed massive damage of the OE as early as 2 days post nasal instillation of SARS-CoV-2, resulting in a major loss of cilia necessary for odour detection. These damages were associated with infection of a large proportion of sustentacular cells but not of olfactory neurons, and we did not detect any presence of the virus in the olfactory bulbs. We observed massive infiltration of immune cells in the OE and lamina propria of infected animals, which may contribute to the desquamation of the OE. The OE was partially restored 14 days post infection. Anosmia observed in COVID-19 patient is therefore likely to be linked to a massive and fast desquamation of the OE following sustentacular cells infection with SARS-CoV-2 and subsequent recruitment of immune cells in the OE and lamina propria.

neuroscience↗

bioRxiv2019

The Intestinal Microbiota Contributes To The Control Of Highly Pathogenic H5N9 Influenza Virus Replication In Ducks

Ducks usually show little or no clinical signs following highly pathogenic avian influenza virus infection. In order to analyze if the gut microbiota could contribute to the control of influenza virus replication in ducks, we used a broad-spectrum oral antibiotic treatment to deplete the gut microbiota before infection with a highly pathogenic H5N9 avian influenza virus. Antibiotic-treated ducks and non-treated control ducks did not show any clinical signs following H5N9 virus infection. We did not detect any difference in virus titers neither in the respiratory tract, nor in the brain and spleen. However, we found that antibiotic-treated H5N9 virus infected ducks had significantly increased intestinal virus excretion at day 3 and 5 post-infection. This was associated with a significantly decreased antiviral immune response in the intestine of antibiotic-treated ducks. Our findings highlight the importance of an intact microbiota for an efficient control of avian influenza virus replication in ducks.\n\nIMPORTANCEDucks are frequently infected with avian influenza viruses belonging to multiple subtypes. They represent an important reservoir species of avian influenza viruses, which can occasionally be transmitted to other bird species or mammals, including humans. Ducks thus have a central role in the epidemiology of influenza virus infection. Importantly, ducks usually show little or no clinical signs even following infection with a highly pathogenic avian influenza virus. We provide evidence that the intestinal microbiota contributes to the control of influenza virus replication in ducks by modulating the antiviral immune response. Ducks are able to control influenza virus replication more efficiently when they have an intact intestinal microbiota. Therefore, maintaining a healthy microbiota by limiting perturbations to its composition should contribute to prevention of avian influenza virus spread from the duck reservoir.

microbiology↗