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2024 re-emergence of coxsackievirus A24 variant causing an outbreak of acute hemorrhagic conjunctivitis in the South West Indian Ocean
No full textInternational audienceIn early 2024, an outbreak of acute hemorrhagic conjunctivitis occurred in Mayotte and in Madagascar, two islands in the Indian Ocean. Real-time diagnosis and genotyping identified a different lineage of coxsackievirus A24 variant (CVA24v) from the current Asian outbreak. Although no recombination event had been detected in all previously reported CVA24v-associated outbreaks associated with the subgenotype IV, we characterized a putative recombinant strain by full-length genome sequencing
Transmission Pathways of Zoonotic Influenza Viruses and Influencing Factors: A Systematic Review of Recent Findings
No full textInternational audienceRecent outbreaks of zoonotic influenza viruses underscored the need for a deeper understanding of transmission pathways and factors influencing spillover events. Understanding the combined effects of environmental conditions, host interactions, and viral adaptations is essential for effective preparedness and response. The WHO public health research agenda for influenza, revised in 2017, recommended research to further define the host-to-host transmission pathways of influenza type A viruses. Since 2017, important research has been conducted, and the global health landscape has changed. Therefore, there is a need to review the transmission pathway studies conducted during the last eight years. We conducted a systematic analysis following the PRISMA guidelines on 7490 PubMed records from 2017 to 2024, of which 219 records were retained. This review evaluates research on zoonotic influenza virus transmission among wild and domestic animals and cross-species transmission to humans. By examining pathways, host, environmental, and viral factors, this review identified key findings and research gaps. Research remains limited in critical areas including transmission pathways among diverse animals, role of environmental factors, and zoonotic potential across regions. Addressing these gaps is essential for improving public health strategies. This review highlights the necessity of integrating a One Health approach in addressing zoonotic influenza risks
Host-parasite coevolution leads to underwater respiratory adaptations in extreme diving insects, seal lice (Lepidophthirus macrorhini)
No full textInternational audienceLice are obligate ectoparasites that have co-evolved with their hosts, particularly during the transition of mammals from terrestrial to amphibious habits, as sea lions, seals and walruses, and have undergone parallel adaptations to the extreme conditions of the deep sea. By combining morphological, physiological and genomic analyses, we are shedding light on a key process for surviving prolonged submersion: respiration. Under water, lice immobilise, close their spiracles, reduce their oxygen consumption to a minimum and breathe through their tegument. The presence of haemoglobin genes in their genome also strongly suggests the ability to store oxygen during host dives. Remarkably, seal lice have no anatomical features or physiological capabilities that distinguish them from other insects. This reinforces the idea that the absence of insects in the deep sea is not due to any inherent limitations in their form or function, but rather a result of their evolutionary pathways
Definition of clinical immunology around the globe
No full textInternational audienceImmunology has gradually become a core part of many medical specialties. Immune cells and immune mediators are now known to participate in the pathogenesis of a wide variety of diseases and therapies based on the modulation of immune function are increasingly used. Traditionally, clinical immunologists have studied patients with inborn errors of immunity (IEI), previously known as primary immunodeficiencies, and with allergic conditions. More recently, clinical immunology has become involved with a broader array of disorders. The Clinical Immunology Committee of the International Union of Immunological Societies set out to understand how clinical immunologists perceive their specialty to identify similarities and differences in training and practice around the globe. For this purpose, a specific questionnaire was designed and distributed amongst our member societies. More than 500 participants answered the questionnaire, 80% of whom had completed their training. Roughly two thirds of respondents were physicians directly involved in patient care. We found that though the number of diseases and processes in which immune mechanisms are involved has considerably grown, 90% of participants agree with the 1993 World Health Organization definition of Clinical Immunology. We propose that the increased complexity of the field opens a need for multidisciplinary teams of clinicians and basic researchers and for a broader training of specialists
Use of Recombinant Chikungunya Virus expressing Nanoluciferase to Identify Chondrocytes as Target Cells in an Immunocompetent Mouse Model
No full textInternational audienceChikungunya virus (CHIKV) induces predominantly symptomatic infections, marked by fever, myalgia, rash and polyarthralgia that can last for up to 3 years after infection. Understanding the pathophysiology of CHIKV in the joints is challenging due to limited access to biological samples. Using a reporter virus expressing Nanoluciferase in a mouse model allowed us to monitor viral replication in real-time during acute and postacute phases. We showed viral replication in chondrocyte containing tissue in the metatarsi joints and confirmed with ex vivo analyses viral replication in leg bones and articular cartilages with histological evidence of focal erosive lesions and periarticular inflammation. Moreover, human chondrocytes prove susceptible to CHIKV infection, exhibiting viral production and bioluminescence activity. CHIKV induced apoptosis, the up-regulation of markers associated with cartilage remodeling and altered cytokine production. Our study provides insights into the ability of CHIKV to infect articular cartilages, shedding light on the mechanisms of alphaviral arthritis
Is malathion oncogenic for mosquitoes? A transcriptomic and histological study of adults derived from malathion exposed larvae
No full textInternational audienceMalathion is a widely used pesticide with potentially oncogenic properties and may have deleterious effects on organism health and fitness. Although malathion use is now restricted in the European Union, it remains widely used for public health campaigns in other parts of the world, particularly for mosquito control. Understanding its sublethal and long-term effects is thus essential, both for evaluating its ecotoxicological impacts and for anticipating resistance mechanisms. However, empiric data on its effects in wild organisms -especially in invertebrates -remain limited. Here, we quantitatively investigated whether larval exposure to environmentally realistic concentrations of malathion could affect mosquito tissue structure and gene expression profiles of adult Aedes aegypti (yellow fever mosquitoes), using both RNA-seq and histological approaches. Results show no neoplastic or pre-neoplastic lesions in adults exposed to malathion during larval development, contrary to previous studies in other organisms showing carcinogenic effects of malathion. However, our differential gene expression analyses revealed significant changes in genes related to mitochondrial function, energy metabolism, and detoxification pathways, suggesting significant physiological impacts of malathion in adults after early-life pesticide exposure. Notably, females exhibited stronger transcriptomic responses than males, including the upregulation of genes involved in detoxification (e.g., P450 cytochromes), olfactory perception, and stress response, with potential consequences for resistance mechanisms. Our findings underscore the ability of mosquitoes to mount transient molecular responses to environmental pollutants, potentially contributing to the long-term selection of metabolic resistance traits -an outcome with important implications for vector control strategies
HR-MS Analysis of the Covalent Binding of Edaravone to 5-Formylpyrimidine Bases and a DNA Oligonucleotide Containing a 5-Formylcytidine Residue.
No full textInternational audienceRationaleEdaravone (EDA) is a radical scavenger and an antioxidant drug approved to treat amyotrophic lateral sclerosis and used as a research tool to explore treatment of neurodegenerative diseases and cancers. It is also a reactive agent, known as PMP (1-phenyl-3-methyl-5-pyrazolone), used for the analysis of polysaccharides composition. EDA can react with sugars and aromatic aldehydes. In this context, we have investigated the reactivity of EDA toward the biologically relevant formylated nucleobases, nucleosides, and an oligonucleotide containing a formylated residue.MethodsThe formation of both mono- and bis-adducts between EDA and the formylated nucleobases (5-formyluracil (5fU) and 5-formylcytosine (5fC)) or the corresponding nucleosides 5-fdU and 5-fdC was characterized using high-resolution mass spectrometry (HR-MS). Similarly, the covalent binding of EDA to an 8-mer palindromic oligonucleotide d (TATG[*C]ATA) containing a single 5-fdC residue [*C] under physiological conditions was investigated using mass spectrometry.ResultsFor the first time, EDA is shown to react with formylated pyrimidines. Covalent and stable adducts were identified. EDA was found to react efficiently with the formylated oligonucleotide to generate mono- and bis-adducts. The rate of formation of the mono-adduct was five times higher than that of the bis-adduct. The reaction of EDA with aldehydic DNA modifications such as 5fU/5fC may have important consequences in terms of gene expression.ConclusionsThese observations raise implications for an epigenetic contribution to the mechanism of action of EDA. The biological implications of our in vitro results are discussed, notably in the frame of neurodegenerative diseases and cancers
Retroviral adapters hijack the RNA helicase UPF1 in a CRM1/XPO1-dependent manner and reveal proviral roles of UPF1
No full textInternational audienceThe hijacking of CRM1 export is an important step of the retroviral replication cycle. Here, we investigated the consequences of this hijacking for the host. During HTLV-1 infection, we identified that this hijacking by the viral protein Rex favours the association between CRM1 and the RNA helicase UPF1, leading to a decreased affinity of UPF1 for cellular RNA and its nuclear retention. As a consequence, we found that the nonsense-mediated mRNA decay (NMD), known to have an antiviral function, was inhibited. Corroborating these results, we described a similar process with Rev, the functional homolog of Rex from HIV-1. Unexpectedly, we also found that, for HTLV-1, this process is coupled with the specific loading of UPF1 onto vRNA, independently of NMD. In this latter context, UPF1 positively regulates several steps of the viral replication cycle, from the nuclear export of vRNA to the production of mature viral particles
Transferability of European-derived Alzheimer’s Disease Polygenic Risk Scores across Multi-Ancestry Populations
No full textInternational audienceA polygenic score (PGS) for Alzheimer’s disease (AD) was recently derived from data on genome-wide significant loci in European ancestry populations. We applied this PGS to populations in 17 European countries and observed a consistent association with AD risk, age at onset, and cerebrospinal fluid levels of AD biomarkers, independently of apolipoprotein E (APOE) . This PGS was also associated with the AD risk in many other populations of diverse ancestries. A cross-ancestry polygenic risk score (PRS) improved the association with AD risk in most of the multi-ancestry populations tested when the APOE region was included. Lastly, we found that the PGS/PRS, captured AD-specific information because the association weakened as the diagnosis was broadened. In conclusion, a simple PGS captures the AD-specific genetic information that is common to populations of different ancestries, but studies of more diverse populations are still needed for a better characterization of the AD genetics
One Health Field Approach Applied to Leptospirosis: A Systematic Review and Meta-Analysis Across Humans, Animals and the Environment
No full textInternational audienceLeptospirosis is a neglected zoonosis transmitted through urine of infected hosts or contaminated environments. The transmission of bacteria between humans, animals, and the environment underscores the necessity of a One Health approach.Methods. We conducted a systematic review to identify significant findings and challenges in One Health research on leptospirosis, focusing on studies involving sampling in ≥2 of the 3 compartments: human, animal, and environment. We searched in PubMed, Web of Science, Medline, Scopus, and ScienceDirect from 1 January 1918 to 31 December 2022. We assessed risk of bias in studies using Joanna Briggs Institute tools and performed a meta-analysis to identify links between One Health compartments.Results. Of 1082 leptospirosis studies with sampling, 102 multicompartmental studies conducted between 1972 and 2022 were included: 70 human-Animal, 18 animal-environment, 4 human-environment, and 10 across all compartments. Various methodological weaknesses were identified, from study design to statistical analysis. Meta-regressions identified positive associations between human and animal seroprevalences, particularly with livestock and with wild nonrodent animals, and a link between the environmental positivity rate and domestic animal seroprevalence. Our analysis was constrained by the limited number of studies included and by the quality of protocols.Conclusions. This 50-year overview of One Health field approach to leptospirosis highlights the critical need for more robust, wellsupported One Health research to clarify the transmission dynamics and identify risk factors of zoonoses