Biology subjects

Lesellier, S.

Publications and source records attributed to Lesellier, S..

4 recordsLinked to original sources

bioRxiv2026

Potential for real-time health and welfare monitoring in experimental rabies infection in red fox (Vulpes vulpes) using implants

Monitoring and improving animal health and welfare is a pressing need. Technological advances are increasing our ability to do so in a range of settings but currently, there are limited uses in experimental settings for less common model animals. Red foxes (Vulpes vulpes) are maintained by the French National Agency for Food, Environmental, and Occupational Health and Safety (ANSES) for regulatory and research purposes, primarily related to its role as a European Union and French Reference Laboratory for rabies and Echinococcus spp. In 2022, four foxes were surgically fitted with internal implants that recorded body temperature and activity levels and subsequently inoculated with rabies virus (RABV). Retrospectively, we tested the potential of these two variables to provide an early warning for the onset of rabies symptoms. We applied two anomaly detection algorithms (Shewhart and EWMA) with varying confidence levels to the data sets and compared how early the different models could detect significant changes while limiting false alarms during the calibration period. We hypothesized that body temperatures would rise significantly and foxes would significantly alter their activity levels at the beginning of infection, both at an earlier stage than is detectable through direct observation. We found that foxes significantly changed their activity during infection. We were best able to detect these changes using the EWMA algorithm, in some cases producing consecutive alarms up to two weeks before the death of an animal, while limiting false alarms. We found no evidence of fever in any of the infected foxes and body temperature did not appear to be a reliable indicator of foxes health. While here we applied our methods to a particularly severe and rarely implemented model with a very small sample size, this proof of concept illustrates the potential of these methods for a wide range of other situations that would benefit from similar long-term monitoring, including experimental protocols with milder clinical signs and routine monitoring for unexpected declines in health or welfare.

animal behavior and cognition↗

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

Hamster and ferret experimental infection with intranasal low dose of a single strain of SARS-CoV-2

Understanding the pathogenesis of the SARS-CoV-2 infection is key to develop preventive and therapeutic strategies against COVID-19, in the case of severe illness but also when the disease is mild. The use of appropriate experimental animal models remains central in the in-vivo exploration of the physiopathology of infection and antiviral strategies. This study describes SARS-CoV-2 intra-nasal infection in ferrets and hamsters with low doses of low-passage SARS-CoV-2 clinical French isolate UCN19, describing infection levels, excretion, immune responses and pathological patterns in both animal species. Individual infection with 103 pfu SARS-CoV-2 induced a more severe disease in hamsters than in ferrets. Viral RNA was detected in the lungs of hamsters but not of ferrets and in the brain (olfactive and/or spinal bulbs) of both species. Overall, the clinical disease remained mild, with serological responses detected from 7 days and 10 days post inoculation in hamsters and ferrets respectively. Virus became undetectable and pathology resolved within 14 days. The kinetics and levels of infection can be used in ferrets and hamsters as experimental models for understanding the pathogenicity of SARS-CoV-2, and testing the protective effect of drugs.

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↗