The feather epithelium contributes to the dissemination and ecology of clade 2.3.4.4b H5 high pathogenicity avian influenza viruses in ducks

Immature feathers are known replication sites for high pathogenicity avian influenza viruses (HPAIVs) in poultry. However, it is unclear whether feathers play an active role in viral transmission. This study aims to investigate the contribution of the feather epithelium to the dissemination of clade 2.3.4.4b goose/Guangdong/1996 lineage H5 HPAIVs in the environment, based on natural and experimental infections of domestic mule and Muscovy ducks. During the 2016-2022 outbreaks, H5 HPAIVs exhibited persistent and marked feather epitheliotropism in naturally infected commercial ducks. Infection of the feather epithelium resulted in epithelial necrosis and disruption, as well as the production and environmental shedding of infectious virions. Viral and feather antigens colocalized in dust samples obtained from poultry barns housing naturally infected birds. In summary, the feather epithelium contributes to viral replication, and it is a likely source of environmental infectious material. This underestimated excretion route could greatly impact the ecology of HPAIVs, facilitating airborne and preening-related infections within a flock, and promoting prolonged viral infectivity and long-distance viral transmission between poultry farms

Mécanismes d'adaptation des virus Influenza A : Etude des interactions entre protéine virale NS1 et protéines cellulaires

National audienc

Protection against Bovine Respiratory Syncytial Virus Afforded by Maternal Antibodies from Cows Immunized with an Inactivated Vaccine

The passive protection afforded by the colostrum from cattle that were vaccinated prepartum with an inactivated combination vaccine against the bovine respiratory syncytial virus (BRSV) was evaluated after an experimental challenge of calves. Pregnant cows without or with a low ELISA and neutralizing BRSV antibody titers were twice vaccinated or not vaccinated, the last immunization being at one month prior to calving. Vaccination was followed by a rapid increase in BRSV antibody titers after the second immunization. Twenty-eightnewborn calves were fed during the 6 h following birth, with 4 L of colostrum sourced from vaccinated cows (14 vaccine calves) or non-vaccinated cows (14 control calves) and were challenged with BRSV at 21 days of age. We showed that maternal immunity to BRSV provides a significant reduction in the clinical signs of BRSV in calves, especially for severe clinical forms. This protection was correlated with reduced BRSV detection in the lower respiratory tract but not in nasal swabs, indicating an absence of protection against BRSV nasal excretion. Finally, transcriptomic assays in bronchoalveolar lavages showed no statistical differences between groups for chemokine and cytokine mRNA transcriptions, with the exception of the overexpression of IL-9 at days 6 and 10 post-challenge, and a severe downregulation of CXCL-1 at day 3 post-challenge, in the vaccine group

Neuronal retrograde transport of Borna disease virus occurs in signalling endosomes

International audienceLong-range axonal retrograde transport is a key mechanism for the cellular dissemination of neuroinvasive viruses, such as Borna disease virus (BDV), for which entry and egress sites are usually distant from the nucleus, where viral replication takes place. Although BDV is known to disseminate very efficiently in neurons, both in vivo and in primary cultures, the modalities of its axonal transport are still poorly characterized. In this work, we combined different methodological approaches, such as confocal microscopy and biochemical purification of endosomes, to study BDV retrograde transport. We demonstrate that BDV ribonucleoparticles (composed of the viral genomic RNA, nucleoprotein and phosphoprotein), as well as the matrix protein, are transported towards the nucleus into endocytic carriers. These specialized organelles, called signalling endosomes, are notably used for the retrograde transport of neurotrophins and activated growth factor receptors. Signalling endosomes have a neutral luminal pH and thereby offer protection against degradation during long-range transport. This particularity could allow the viral particles to be delivered intact to the cell body of neurons, avoiding their premature release in the cytoplasm

Reasons for non-vaccination in French rheumatoid arthritis and spondyloarthritis patients

International audienc

A viral peptide that targets mitochondria protects against neuronal degeneration in models of Parkinson's disease

International audienceMitochondrial dysfunction is a common feature of many neurodegenerative disorders, notably Parkinson's disease. Consequently, agents that protect mitochondria have strong therapeutic potential. Here, we sought to divert the natural strategy used by Borna disease virus (BDV) to replicate in neurons without causing cell death. We show that the BDV X protein has strong axoprotective properties, thereby protecting neurons from degeneration both in tissue culture and in an animal model of Parkinson's disease, even when expressed alone outside of the viral context. We also show that intranasal administration of a cell-permeable peptide derived from the X protein is neuroprotective. We establish that both the X protein and the X-derived peptide act by buffering mitochondrial damage and inducing enhanced mitochondrial filamentation. Our results open the way to novel therapies for neurodegenerative diseases by targeting mitochondrial dynamics and thus preventing the earliest steps of neurodegenerative processes in axons

Etude des interactions entre le virus Influenza D et Mycoplasma bovis dans le cadre des bronchopneumonies infectieuses chez les jeunes bovins

International audienc

EPAC1 Pharmacological Inhibition with AM-001 Prevents SARS-CoV-2 and Influenza A Virus Replication in Cells

International audienceThe exceptional impact of the COVID-19 pandemic has stimulated an intense search for antiviral molecules. Host-targeted antiviral molecules have the potential of presenting broad-spectrum antiviral activity and are also considered as less likely to select for resistant viruses. In this study, we investigated the antiviral activity exerted by AM-001, a specific pharmacological inhibitor of EPAC1, a host exchange protein directly activated by cyclic AMP (cAMP). The cAMP-sensitive protein, EPAC1 regulates various physiological and pathological processes but its role in SARS-CoV-2 and influenza A virus infection has not yet been studied. Here, we provide evidence that the EPAC1 specific inhibitor AM-001 exerts potent antiviral activity against SARS-CoV-2 in the human lung Calu-3 cell line and the African green monkey Vero cell line. We observed a concentration-dependent inhibition of SARS-CoV-2 infectious viral particles and viral RNA release in the supernatants of AM-001 treated cells that was not associated with a significant impact on cellular viability. Furthermore, we identified AM-001 as an inhibitor of influenza A virus in Calu-3 cells. Altogether these results identify EPAC1 inhibition as a promising therapeutic target against viral infections