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Biology subjects

Servat, A.

Publications and source records attributed to Servat, A..

4 recordsLinked to original sources

Infectious potential and circulation of SARS-CoV-2 in wild rats

Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, a wide range of animal species (pets, mink...) have been naturally infected with this betacoronavirus. The emergence of new variants has increased the ability of SARS-CoV-2 to infect species that were not susceptible to the "original" SARS-CoV-2, such as mice and rats. This work attempted to evaluate the role of urban rats in the SARS-CoV-2 transmission by combining surveillance studies of rat populations in urban environments, in vivo experimental inoculation of SARS-CoV-2 and comparative viral-receptor interaction in silico analyses. We studied the circulation of SARS-CoV-2 in wild Rattus norvegicus (n=401) captured in urban areas and sewage systems of several French cities. Except for 3 inconclusive samples (2/75 from Bordeaux and 1/261 from Lyon) none of the 353 sera tested showed anti-SARS-CoV-2 antibodies by microsphere immunoassay. However, the 3 inconclusive sera samples were negative by virus neutralisation assay. No SARS-CoV-2 viral RNA was detected in all lungs collected from the 401 captured urban brown rats. In complement, four rat groups (two wild-type colonies, Rattus norvegicus and Rattus rattus, and two laboratory strains, Sprague-Dawley and Wistar) were inoculated with the SARS-CoV-2 Omicron BA.5. At 4 days post-inoculation, no infectious viral particles were detected in the lungs and upper respiratory tract (URT) while viral RNA was detected at a low level only in the URT of all groups. In addition, seroconversion was observed 14 days after inoculation in the four groups. By molecular modelling, the Omicron BA.5 receptor binding domain (RBD) had lower affinities for Rattus norvegicus and Rattus rattus ACE2 than Homo sapiens ACE2. Based on these results the SARS-CoV-2 Omicron BA.5 was unable to infect laboratory and wild type rats. In addition, Rattus norvegicus collected for this study in different areas of France were not infected with SARS-CoV-2.

microbiology↗

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↗

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↗

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↗