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Biology subjects

Huet, H.

Publications and source records attributed to Huet, H..

4 recordsLinked to original sources

Identification and characterization of a non-peptidic cyclophilin ligand with antiviral activity against feline and porcine α-coronaviruses.

Coronaviruses (CoVs) are emerging pathogens that have been extensively studied over the last 20 years and can cause acute respiratory diseases in humans, as exemplified by the SARS-CoV-2 pandemic. Coronaviruses are also known for their importance in veterinary medicine, being responsible for severe pathologies in pets and livestock. These include Feline Infectious Peritonitis Virus (FIPV), which causes a fatal disease in cats. In livestock, porcine coronaviruses such as Transmissible Gastroenteritis Virus (TGEV) and Porcine Epidemic Diarrhoea Virus (PEDV) are the causative agents of an acute enteric disease in piglets with a high mortality rate and a significant impact on the pork industry. In addition, animal coronaviruses may represent a zoonotic reservoir. Therefore, efficient antiviral strategies are required to inhibit the multiplication of coronaviruses infecting various animal species. Here, we synthesized 20 small-molecule ligands that target cyclophilins, a family of cellular chaperons hijacked by several viruses including CoVs. We screened their antiviral activity against feline and porcine alpha-CoVs, and identified a compound, F83233, as a potent inhibitor of FIPV, TGEV and PEDV replication at micromolar concentrations that was effective in feline, porcine and simian cells. As cyclophilins are highly conserved among mammals, F83233 could be a promising antiviral to treat different animal and zoonotic coronaviruses.

microbiology↗

SARS-CoV-2 Delta variant induces severe damages in the nasal cavity from the first day post-infection in the Syrian hamster model.

SARS-CoV-2 replication initiates in the nasal cavity and can spread to the lower respiratory tract. However, the early physiopathological events that occur in the nasal cavity after infection remain poorly understood. In this study, we investigated the initial steps of viral infection from 1 day post-infection (dpi) in Syrian hamsters infected with SARS-CoV-2 D614G, Delta and Omicron (BA.1) variants and compared them with animals sacrificed at 4 dpi. While the level of viral replication in the nasal turbinates of the three groups of hamsters was equivalent at 4dpi, the amount of viral RNA at 1dpi was higher in D614G- and Delta-infected animals than in the Omicron group. No difference in viral RNA levels or inflammatory markers in the nasal turbinates was observed between D614G- and Delta-infected animals, except for a significantly higher level of IFN-{lambda} in the Delta group at 1dpi. Additionally, histological analysis revealed a more rapid diffusion of the Delta virus reaching the posterior zone of the nasal cavity at 1dpi inducing significant damage to the olfactory epithelium. At the same time, the D614G and Omicron infections were essentially restricted to the anterior part of the nasal cavity with less damage observed. Consistently, viral replication was already effective in the lungs of all Delta- infected hamsters at 1 dpi, but only in two of the six D614G animals. Our results highlight the importance of studying viral infection in the nasal cavity very early after infection with a spatial approach to better understand the physiopathology of the different SARS-CoV-2 variants.

microbiology↗

Disruption of fish gut microbiota composition and holobiont metabolome by cyanobacterial blooms

BackgroundCyanobacterial blooms are one of the most common stress encountered by metazoans living in freshwater lentic systems such as lakes and ponds. Blooms reportedly impair fish health, notably through oxygen depletion and production of bioactive compounds including cyanotoxins. However, in the times of the "microbiome revolution", it is surprising that so little is still known regarding the influence of blooms on fish microbiota. In this study, an experimental approach is used to demonstrate that blooms affect fish microbiome composition and functions, as well as the metabolome of holobionts. To this end, the model teleost Oryzias latipes is exposed to simulated Microcystis aeruginosa blooms of various intensities in a microcosm setting, and the response of bacterial gut communities is evaluated in terms of composition, metagenome-encoded functions and metabolome profiling. ResultsThe gut bacterial community of O. latipes exhibits marked responses to the presence of M. aeruginosa blooms in a dose-dependent manner. Notably, abundant gut-associated Firmicutes almost disappear, while potential opportunists increase. The holobionts gut metabolome displays major changes, while functions encoded in the metagenome of bacterial partners are more marginally affected. Bacterial communities tend to return to original composition after the end of the bloom suggesting post-bloom resilience, and remain sensitive in case of a second bloom, reflecting a highly reactive gut community. ConclusionIn the context of increasingly frequent and intense blooms worldwide, results point to the relevance of accounting for short- and long-term microbiome-related effects in fish ecology, with potential outcomes relevant to conservation biology as well as aquaculture.

microbiology↗

Subcellular localization of microcystin in the liver and the gonad of medaka fish acutely exposed to microcystin-LR

Among the diverse toxic components produced by cyanobacteria, microcystins (MCs) are one of the most toxic and notorious cyanotoxin groups. Besides their potent hepatotoxicity, MCs have been revealed to induce potential reproductive toxicity in various animal studies. However, little is still known regarding the distribution of MCs in the reproductive organ, which could directly affect reproductive cells. In order to respond to this question, an acute study was conducted in adult medaka fish (model animal) gavaged with 10 {micro}g.g-1 body weight of pure MC-LR. The histological and immunohistochemical examinations reveal an intense distribution of MC-LR within hepatocytes along with a severe liver lesion in the toxin-treated female and male fish. Besides being accumulated in the hepatocytes, MC-LR was also found in the connective tissue of the ovary and the testis, as well as in oocytes and degenerative spermatocyte-like structures. Both liver and gonad play important roles in the reproductive process of oviparous vertebrates. This observation constitutes the first observation of the presence of MC-LR in the reproductive cell of a vertebrate model with in vivo study. Our results, which provide intracellular localization of MC-LR in the gonad, advance our understanding of the potential reproductive toxicity of MC-LR in fish.

cell biology↗