Biology subjects

Kornobis, E.

Publications and source records attributed to Kornobis, E..

At least 19 recordsLinked to original sources

bioRxiv2026

SARS-CoV-2 ORF9b exploits mitochondrial recruitment to TOMM70 for proteasomal protection and tunes inflammatory remodeling during lung infection

Mitochondrial outer membrane proteins are exploited by diverse intracellular pathogens, to modulate cell metabolism and innate sensing pathways. Here, we demonstrate that TOMM70-dependent mitochondrial recruitment is required to protect SARS-CoV-2 ORF9b from proteasomal degradation, a dependency conserved across ORF9b homologs from related coronaviruses. ORF9b mitochondrial recruitment requires the E477 residue of TOMM70, a surface distinct from that used by the parasite Toxoplasma gondii to engage host mitochondria. We further show that TOMM70 is not a passive scaffold: its depletion activates interferon-stimulated gene expression independently of infection and remodels host immunity distinctly from ORF9b, establishing the receptor and viral protein as mechanistically separable. Using ORF9b-deficient SARS-CoV-2, we demonstrate that ORF9b is dispensable for viral replication and pathological responses in human respiratory epithelial cells and lungs of infected golden Syrian hamsters. Omics profiling of SARS-CoV-2 infected lungs revealed an induction of pathways related to COVID-19 in the absence of ORF9b. Notably, ORF9b-deficient virus-infected lungs show elevated expression of C15ORF48, a nuclear-encoded mitochondrial protein that substitutes for Complex IV subunit NDUFA4 to attenuate inflammation. Collectively, we propose that ORF9b is a receptor-gated viral protein whose principal measurable consequence during authentic infection is a restraint on inflammatory respiratory-chain remodeling.

cell biology↗

bioRxiv2026

Stress-responsive Mycobacterium tuberculosis subpopulations manipulate macrophage polarization and can be targeted to limit inflammation

Tuberculosis is characterized by broad clinical heterogeneity that hinders infection control, with differences in lesion development, progression, and treatment outcomes. This complexity is likely associated with Mycobacterium tuberculosis inherent phenotypic variation and its capacity to diversify under host microenvironmental and antimicrobial stressors. Here, we analyze M. tuberculosis at the single-cell and subpopulation level using fluorescent reporters, imaging, transcriptomic, and functional assays. We identify RNA signatures specific to stress-responsive bacilli with translational potential. Focusing on the clinically validated chaperone GroEL2, we find that it correlates with M. tuberculosis growth rate and stress tolerance in vitro and intracellularly. Furthermore, GroEL2 phenotypic diversity influences innate responses in macrophages, which experience different polarization, in turn affecting GroEL2 expression. We also show that targeting GroEL2 impairs pathogen survival and dampens inflammation. This study provides a link between pathogen phenotypic variation and macrophage fates, with implications for early infection outcomes, local disease progression, and subpopulation-targeted interventions.

microbiology↗

bioRxiv2026

High-quality proteins and RNAs extracted from exact same samples for proteomics and RNA-Seq analyses

Back to the 1990 the single step method developed by Chomczynski and Sacchi for RNA isolation was extended for sequential isolation of RNA, DNA and proteins from a same sample. Although the quality of the extracted RNA turned compatible with RNA-Seq analyses, the extraction of the protein fraction from the same sample was time-consuming and resulting in low yield and quality of proteins not compatible with LC-MS proteomic analyses. Here we report a novel procedure by isolating in parallel the protein fraction and the RNA fraction from the same exact minute mosquito samples. We provide evidence that each cognate fractions are compatible with LC-MS proteomic analysis on the one hand and RNA-Seq analysis on the other hand. This protocol is simple, time efficient and adequate for studies involving limited sample size and could be applied easily to a broad range of animal and human samples.

molecular biology↗

bioRxiv2026

Spatial organization of mAbs in complex with the virus glycoprotein determines the success of intravenous rabies therapy

Rabies is a complex disease that has defied efforts to develop an effective treatment. Although it can be successfully prevented through vector control or pre- or post-exposure prophylaxis, no therapeutic options exist for symptomatic rabies, and the disease is still responsible for about 59 000 human deaths each year. Following our successful attempts to use the human monoclonal antibodies RVC20 and RVC58 for intracerebroventricular treatment of rabies, we report here on the effects of these mAbs when administered intravenously and intramuscularly to symptomatic mice. Only a small proportion of mAbs was detected to cross the blood-brain barrier, yet this limited amount sufficiently cleared the viral infection and improved the survival rate of infected mice. Remarkably, these mAbs appeared more effective when used individually than when combined as a cocktail. RVC58 achieved an 80% survival rate, potentially due to its distinct binding topography, potent viral neutralization, and enhanced Fc{gamma}R engagement in the presence of virions. These findings suggest that monotherapy with a single mAb fully capable of engaging Fc{gamma}R may be possible, which could substantially lower the costs and improve treatment accessibility in under-resourced settings, potentially contributing to improved equity of global health. Taken together, this study supports mAb therapy as a promising preclinical approach for symptomatic rabies and provides a foundation for further development of an accessible treatment option.

microbiology↗

bioRxiv2025

Mutant CHCHD10 disrupts cytochrome c oxidation and activates retrograde signaling in a model of cardiomyopathy.

Mutations in CHCHD10, a mitochondrial intermembrane space (IMS) protein implicated in proteostasis and cristae maintenance, cause multi-systemic mitochondrial disease. Heterozygous Chchd10 knock-in mice modeling the human CHCHD10S59L variant associated with Amyotrophic Lateral Sclerosis and Frontotemporal Dementia (ALS-FTD) develop a mitochondrial cardiomyopathy driven by CHCHD10 insolubility and aggregation, which is associated with chronic activation of the mitochondrial integrated stress response (mtISR). Here, we demonstrate that cardiac dysfunction in Chchd10S55L/+ mice carrying the orthologous pathogenic variant is associated with dual defects originating at the onset of disease: (1) early bioenergetic dysfunction linked to defects in the mitochondrial copper homeostasis and the oxidation of cytochrome c and (2) maladaptive mtISR signaling via the OMA1-DELE1-HRI axis. Using Oma1E324Q/E324Qknock-in mice, we show that the catalytic inactivation of the mitochondrial protease OMA1 in Chchd10S55L/+ mice delays cardiomyopathy onset without rescuing CHCHD10 insolubility, proteomic remodeling, cristae defects or OXPHOS impairment, demonstrating that mtISR can be uncoupled from the bioenergetic collapse triggered by mutant CHCHD10. Proteomic profiling of soluble and insoluble mitochondrial proteins in Chchd10S55L/+ mice reveals wide-spread disruptions of mitochondrial proteostasis, including IMS proteins involved in cytochrome c biogenesis. Defective respiration in mutant mitochondria could be rescued by the exogenous addition of cytochrome c, pinpointing IMS proteostasis disruption as a key pathogenic mechanism. Our work reveals that mutant CHCHD10 insolubility compromises metabolic resilience by impairing both mitochondrial bioenergetics and stress adaptation, offering new perspectives for the development of therapeutic targets.

cell biology↗

bioRxiv2025

Natural diversity of telomere length distributions across 100 yeast strains

Telomeres gradually shorten at each cell division and telomerase counteracts this shortening by elongating telomere sequences. This dynamic balance between elongation and shortening results in a steady-state telomere length (TL) distribution. We developed a method for detecting telomeric sequences in Saccharomyces cerevisiae genomes from raw Oxford Nanopore Technologies (ONT) sequencing reads, providing a comprehensive view of TL distributions both genome-wide and at individual chromosome extremities. We analyzed the TL distribution in 100 S. cerevisiae strains, representing the genetic and ecological diversity of the species. Our analysis revealed a large diversity in TL distributions within the species, largely driven by inter-extremity differences, ploidy level, and subtelomere structure. Polyploid strains displayed significantly longer telomeres than diploid and haploid strains, and experiments with artificially generated polyploids in two independent genetic backgrounds confirmed that higher ploidy levels lead to telomere elongation. Furthermore, we found that the subtelomeric Y element exerts two distinct and opposing effects: (i) the presence of Y elements at a chromosome extremity is associated with shorter telomeres in cis, but (ii) the overall Y element content in a strain correlates with longer telomeres. Interestingly, the length of the shortest telomeres remained relatively constant across strains, suggesting a selective constraint at the species level. This study reveals the diversity of TL in S. cerevisiae and highlights key factors shaping TL distributions both genome-wide and at individual chromosome extremities.

genomics↗

bioRxiv2025

Altered RNA-processing provides a mechanistic framework delineating human sex reversal associated with pathogenic variants in the RNA-helicase DHX37

Recurrent heterozygous missense variants in the highly conserved RNA-helicase DHX37, which is required for ribosome biogenesis, are a frequent cause of 46,XY sex-reversal or testis regression syndrome. How these missense variants specifically disrupt testis formation is unknown. Here, we demonstrate that mutant DHX37 proteins retain their ATPase activity and are not associated with stabilization of cellular {beta}-catenin. Transfection of DHX37 p.R674Q mutant protein in an in-vitro cellular model recapitulating human Sertoli cell formation, showed a reduced activation of pro-testis genes compared to the WT protein. The expression of a DHX37 mutant protein in in-vitro derived human Sertoli-like cells (iSLCs) was also associated with global changes in gene expression, predicted to impact basic cellular functions. To define RNA transcripts interacting with either the WT or a mutant (p.R674Q) protein, we combined HyperTRIBE and single-cell full-length RNA-sequencing approaches using iSLCs. Gene ontology analysis indicated that transcripts targeted by WT DHX37 were primarily associated with cytoskeleton organization, including cell motility and cell adhesion. However, in contrast transcripts targeted by the mutated DHX37 protein, were not only associated with cytoskeleton organization but also with protein degradation and cell death. These data provide mechanistic framework that may explain how variants in the DHX37 protein can result in 46,XY sex-reversal through altered RNA networks that are required for the formation and maintenance of the supporting cell lineages of the human testis.

cell biology↗

bioRxiv2024

Hamsters with long Covid exhibits a neurodegenerative signature in the brainstem

After infection with SARS-CoV-2, patients may present with one or more symptoms that appear or persist over time, including fatigue, respiratory, cardiovascular and neurological disorders. Neurological symptoms include anxiety, depression and impaired short-term memory. However, the exact underlying mechanisms of long Covid are not yet decrypted. Using the golden hamster as a model, we provide further evidence that SARS-CoV-2 is neuroinvasive and can persist in the central nervous system, as we found viral RNA and replicative virus in the brainstem after 80 days of infection. Infected hamsters presented a neurodegenerative signature in the brainstem, with overexpression of innate immunity genes, impacted dopaminergic and glutamatergic synapses, altered energy metabolism. Finally, the infected hamsters manifested persistent signs of depression and impaired short-term memory, as well as late-onset signs of anxiety, as a valuable model to study long Covid. Conclusively, we provide evidence that virus-related and neurodegenerative and immunometabolic mechanisms coexist in the brainstem of infected hamsters and contribute to the manifestation of neuropsychiatric and cognitive symptoms. HighlightsO_LISARS-CoV-2 infects and persists in the brainstem of intranasally-inoculated hamsters C_LIO_LIPersistent neuropsychiatric and cognitive consequences are observed in SARS-CoV-2-infected hamsters C_LIO_LIThe brainstem present distinct transcriptome profiles in acute and in long Covid C_LIO_LIThe dopaminergic and glutamatergic systems are affected in long Covid C_LIO_LIThe SARS-CoV-2 infection affects the expression of genes related to neurodegenerative processes in acute and in long Covid C_LI

pathology↗

bioRxiv2024

The SARS-CoV-2 envelope PDZ Binding Motif acts as a virulence factor disrupting host's epithelial cell-cell junctions

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus responsible for the COVID-19 pandemic, has significantly impacted global health, emphasizing the need to understand its pathogenicity and virulence mechanisms. SARS-CoV-2 disrupts the alveolar epithelial barrier and exacerbates airway inflammation, leading to acute respiratory failure, but the molecular details remain unclear. Additionally, SARS-CoV-2 infection causes neurological symptoms, potentially due to its weakly understood ability to cross the blood-brain barrier. The viral multifunctional Envelope (E) protein is crucial for its virulence, playing a key role in virus assembly, budding, and release. The E protein contains a PDZ-binding motif (PBM) that interacts with host PDZ domain-containing proteins, potentially affecting host signaling pathways and contributing to pathogenicity. This study focuses on the E protein PBM and its role in virulence, disrupting respiratory epithelial barriers and exacerbating airway inflammation. We generated recombinant mutant viruses lacking the PBM and conducted both in vitro and in vivo experiments to elucidate its impact on viral fitness, pathogenicity, and effects on the epithelial integrity. In vitro, the viral mutants showed delayed replication and reduced cytopathic effects. In vivo, experiments with hamsters revealed that PBM-deficient viruses caused less weight loss, lower viral loads, and reduced inflammation, indicating decreased pathogenicity. Histological analyses confirmed less airway damage in these hamsters compared to those infected with the wild-type virus. Additionally, PBM-deficient viruses had impaired interactions with tight junction proteins like ZO-1, a PDZ-containing protein, crucial for maintaining epithelial barrier integrity. Our findings also demonstrate that the PBM does not play a significant role in neuroinvasion during the acute phase of infection, as evidenced by comparable viral RNA loads across brain regions in infected hamsters, regardless of PBM presence. Histopathological and transcriptomic analyses further support this observation, suggesting that the PBM primarily affects specific epithelial barriers. Additionally, RNA-seq analysis on lung and brainstem from infected hamsters reveals that the PBM modulates inflammatory and immune responses, with a stronger impact in lung tissue than in the brainstem. PBM-deficient viruses induce lower levels of inflammation and cytokine expression, suggesting PBMs specific role in enhancing viral pathogenicity through the activation of pathways such as NF-{kappa}B and TNF. Thus, the E protein PBM plays a critical role in SARS-CoV-2s fitness, virulence, and pathogenicity, through the disruption of cell junctions and inflammation, underscoring its potential as a target for therapeutic interventions.

pathology↗

bioRxiv2024

Revisiting oxygen toxicity: evolution and adaptation to superoxide in a SOD-deficient bacterial pathogen

Defenses against oxidants are crucial for the virulence of pathogens, with superoxide scavenging enzymes (SOSEs) playing a vital role for most aerobes. However, our knowledge of superoxide adaptation primarily stems from the study of SOSE-encoding bacteria. Here, we investigated the evolution of a naturally SOSE-deficient pathogen (Leptospira spp.), along with the alternative mechanisms it recruits to combat superoxide stress. We demonstrate that emergence of pathogenic Leptospira correlated with SOD loss, but that a long-lasting adaptation to superoxide remains possible. We reveal that cysteine and leucine biosynthesis are the most induced pathways in response to superoxide and demonstrate the importance of sulfur metabolism in superoxide adaptation in this SOSE-deficient model. We also propose cysteine oxidation as a key mediator of superoxide toxicity in the absence of SOSEs. This study challenges our conventional understanding of the oxygen toxicity theory and proposes a new model of superoxide adaptation through metabolic rewiring in bacteria.

microbiology↗

bioRxiv2024

Incomplete lytic cycle of a widespread Bacteroides bacteriophage leads to the formation of defective viral particles

Advances in metagenomics have led to the identification of new intestinal temperate bacteriophages. However, their experimental characterization remains challenging due to a limited understanding of their lysogenic-lytic cycle and the common lack of plaque formation in vitro. In this study we investigated the hankyphage, a widespread transposable phage of prominent Bacteroides symbionts. Hankyphages spontaneously produced virions in laboratory conditions even in the absence of inducer, but virions did not show any evidence of infectivity. To increase virion production and raise the chances of observing infection events, we identified a master repressor of the hankyphage lytic cycle, RepCHP, whose silencing amplified hankyphage gene expression, enhanced replicative transposition and virion production. However, attempts to infect or lysogenize new host cells with different capsular types remained unsuccessful. Transmission electron microscopy and capsid DNA sequencing revealed an abnormal virion morphology and incomplete DNA packaging of the hankyphage, suggesting that it cannot complete its assembly in laboratory conditions for reasons that are yet to be identified. Still, metavirome and phylogenetic analyses were suggestive of hankyphage horizontal transmission. We could also detect the activity of diversity-generating retroelements (DGRs) that mutagenize the hankyphage minor tail fiber, and likely contribute to its broad host range. This study sheds light on the life cycle of this this abundant intestinal bacteriophage and highlights important gaps in our understanding of the factors required for the completion of its life cycle. Elucidating this puzzle will be critical to gain a better understanding of the hankyphage biology and ecological role.

microbiology↗

bioRxiv2023

Dynamic microfluidic single-cell screening identifies pheno-tuning compounds to potentiate tuberculosis therapy

Drug-recalcitrant infections are a leading global-health concern. Bacterial cells benefit from phenotypic variation, which can suggest effective anti-microbial strategies. However, probing phenotypic variation entails spatiotemporal analysis of individual cells that is technically challenging, and hard to integrate into drug discovery. To address this, we developed a flow-controlled multi-condition microfluidic platform suitable for imaging two-dimensional growth of bacterial cells, compressed inside separate microchambers by a soft hydro-pneumatic membrane. With this platform, we implemented a dynamic single-cell screening for compounds that induce a phenotypic change while decreasing cell-to-cell variation, aiming to undermine the bacterial population, making it more vulnerable to other drugs. We first applied this strategy to mycobacteria, as tuberculosis poses a major public-health threat. Our top hit impairs Mycobacterium tuberculosis via a peculiar mode of action and enhances other anti-tubercular drugs. This work proves that pheno-tuning compounds represent a successful approach to tackle pathogens that are increasingly difficult to treat.

microbiology↗

bioRxiv2023

BioConvert: a comprehensive format converter for life sciences

AO_SCPLOWBSTRACTC_SCPLOWBioinformatics is a field known for the numerous standards and formats that have been developed over the years. This plethora of formats, sometimes complementary, and often redundant, poses many challenges to bioinformatics data analysts. They constantly need to find the best tool to convert their data into the suitable format, which is often a complex, technical and time consuming task. Moreover, these small yet important tasks are often difficult to make reproducible. To over-come these difficulties, we initiated BioConvert, a collaborative project to facilitate the conversion of life science data from one format to another. BioConvert aggregates existing software within a single framework and complemented them with original code when needed. It provides a common interface to make the user experience more streamlined instead of having to learn tens of them. Currently, BioConvert supports about 50 formats and 100 direct conversions in areas such as alignment, sequencing, phylogeny, and variant calling. In addition to being useful for end-users, BioConvert can also be utilized by developers as a universal benchmarking framework for evaluating and comparing numerous conversion tools. Additionally, we provide a web server implementing an online user-friendly interface to BioConvert, hence allowing direct use for the community.

bioinformatics↗

bioRxiv2023

Escherichia coli aggregates mediated by native or synthetic adhesins exhibit both core and adhesin-specific transcriptional responses

Bacteria can rapidly tune their physiology and metabolism to adapt to environmental fluctuations. In particular, they can adapt their lifestyle to the close proximity of other bacteria or presence of different surfaces. However, whether these interactions trigger transcriptomic responses is poorly understood. We used a specific set up of E. coli strains expressing native or synthetic adhesins mediating bacterial aggregation to study the transcriptomic changes of aggregated compared to non-aggregated bacteria. Our results show that following aggregation, bacteria exhibit a core response independent of the adhesin type, with differential expression of 56.9% of the coding genome, including genes involved in stress response and anaerobic lifestyle. Moreover, when aggregates were formed via a naturally expressed E. coli adhesin (Antigen 43), the transcriptomic response of the bacteria was more exaggerated compared to aggregates formed via a synthetic adhesin. This suggests that the response to aggregation induced by native E. coli adhesins could have been finely tuned during bacterial evolution. Our study therefore provides insights on the effect of self-interaction in bacteria and allows a better understanding of why bacterial aggregates exhibit increased stress tolerance. ImportanceFormation of bacterial aggregates has an important role in both clinical and ecological contexts. Although these structures have been previously shown to be more resistant to stressful conditions, the genetic basis of this stress tolerance associated with the aggregate lifestyle is poorly understood. Surface sensing mediated by different adhesins can result in varying changes on bacterial physiology. However, whether adhesin-adhesin interactions as well as the type of adhesin mediating aggregation affects bacterial cell physiology is unknown. By sequencing the transcriptomes of aggregated and non-aggregated cells expressing native or synthetic adhesins, we characterized the effects of aggregation and adhesin type on E. coli physiology.

microbiology↗

bioRxiv2022

142 telomere-to-telomere assemblies reveal the genome structural landscape in Saccharomyces cerevisiae

As population genomics is transitioning from single reference genomes to pangenomes, major improvements in terms of genome contiguity, phylogenetic sampling, haplotype phasing and structural variant (SV) calling are required. Here, we generated the Saccharomyces cerevisiae Reference Assembly Panel (ScRAP) comprising 142 reference-quality genomes from strains of various geographic and ecological origins that faithfully represent the genomic diversity and complexity of the species. The ca. 4,800 non-redundant SVs we identified impact the expression of genes near the breakpoints and contribute to gene repertoire evolution through disruptions, duplications, fusions and horizontal transfers. We discovered frequent cases of complex aneuploidies, preferentially involving large chromosomes that underwent large SVs. We also characterized the evolutionary dynamics of complex genomic regions that classically remain unassembled in short read-based projects, including the 5 Ty families and the 32 individual telomeres. Overall, the ScRAP represents a crucial step towards establishing a high-quality, unified and complete S. cerevisiae pangenome.

genomics↗

bioRxiv2021

Mitochondrial fission process 1 (MTFP1) controls bioenergetic efficiency and prevents inflammatory cardiomyopathy and heart failure in mice

Mitochondria are paramount to the metabolism and survival of cardiomyocytes. Here we show that Mitochondrial Fission Process 1 (MTFP1) is essential for cardiac structure and function. Constitutive knockout of cardiomyocyte MTFP1 in mice resulted in adult-onset dilated cardiomyopathy (DCM) characterized by sterile inflammation and cardiac fibrosis that progressed to heart failure and middle-aged death. Failing hearts from cardiomyocyte-restricted knockout mice displayed a general decline in mitochondrial gene expression and oxidative phosphorylation (OXPHOS) activity. Pre-DCM, we observed no defects in mitochondrial morphology, content, gene expression, OXPHOS assembly nor phosphorylation dependent respiration. However, knockout cardiac mitochondria displayed reduced membrane potential and increased non-phosphorylation dependent respiration, which could be rescued by pharmacological inhibition of the adenine nucleotide translocase ANT. Primary cardiomyocytes from pre-symptomatic knockout mice exhibited normal excitation-contraction coupling but increased sensitivity to programmed cell death (PCD), which was accompanied by an opening of the mitochondrial permeability transition pore (mPTP). Intriguingly, mouse embryonic fibroblasts deleted for Mtfp1 recapitulated PCD sensitivity and mPTP opening, both of which could be rescued by pharmacological or genetic inhibition of the mPTP regulator Cyclophilin D. Collectively, our data demonstrate that contrary to previous in vitro studies, the loss of the MTFP1 promotes mitochondrial uncoupling and increases cell death sensitivity, causally mediating pathogenic cardiac remodeling.

physiology↗

bioRxiv2021

Differential transcriptomic response of Anopheles arabiensis to Plasmodium vivax and Plasmodium falciparum infection

Plasmodium vivax malaria is now recognized as the second most dangerous parasitic threat to human health with the regular decrease of Plasmodium falciparum worldwide over recent decades. A very limited numbers of studies address the interaction of P. vivax with its Anopheles mosquito vectors. Those studies were conducted in P. vivax endemic countries with P.vivax local major vectors for which limited genomic and genetic tools are available. Despite the presence of P. vivax in several African countries and increasing reports on its occurrence in many others, there is virtually no data on the molecular responses of Anopheles arabiensis, a major African mosquito vector, to P. vivax, which limits the development of further "mosquito-targeted" interventions aimed at reducing P. vivax transmission. Taking advantage of the situation of Madagascar where P. falciparum, P. vivax and An. arabiensis are present, we explore the molecular responses of An. arabiensis towards these two human malaria parasites. RNA sequencing on RNAs isolated from mosquito midguts dissected at the early stage of infection (24 hours) was performed using mosquitoes fed on the blood of P. vivax and P. falciparum gametocyte carriers in a field station. From a de novo assembly of An. arabiensis midgut total RNA transcriptome, the comparative analysis revealed that a greater number of genes were differentially expressed in the mosquito midgut in response to P. vivax (209) than to P. falciparum (81). Among these, 15 common genes were identified to be significantly expressed in mosquito midgut 24 hours after ingesting P. vivax and P. falciparum gametocytes, including immune responsive genes and genes involved in amino-acid detoxification pathways. Importantly, working with both wild mosquitoes and field circulating parasites, our analysis revealed a strong mosquito genotype by parasite genotype interaction. Our study also identified 51 putative long non-coding RNAs differentially expressed in An. arabiensis mosquito infected midgut. Among these, several mapped to the published An. arabiensis genome at genes coding immune responsive genes such as gambicin 1, leucine-rich repeat containing genes, either on sense or antisense strands. This study constitutes the first comparison of An. arabiensis molecular interaction with P. vivax and P. falciparum, investigating both coding and long non-coding RNAs for the identification of potential transcripts, that could lead to the development of novel approaches to simultaneously block the transmission of vivax and falciparum malaria.

microbiology↗

bioRxiv2020

COVID-19-associated olfactory dysfunction reveals SARS-CoV-2 neuroinvasion and persistence in the olfactory system

While recent investigations have revealed viral, inflammatory and vascular factors involved in SARS-CoV-2 lung pathogenesis, the pathophysiology of neurological disorders in COVID-19 remains poorly understood. Yet, olfactory and taste dysfunction are rather common in COVID-19, especially in pauci-symptomatic patients which constitutes the most frequent clinical manifestation of the infection. We conducted a virologic, molecular, and cellular study of the olfactory system from COVID-19 patients presenting acute loss of smell, and report evidence that the olfactory epithelium represents a highly significant infection site where multiple cell types, including olfactory sensory neurons, support cells and immune cells, are infected. Viral replication in the olfactory epithelium is associated with local inflammation. Furthermore, we show that SARS-CoV-2 induces acute anosmia and ageusia in golden Syrian hamsters, both lasting as long as the virus remains in the olfactory epithelium and the olfactory bulb. Finally, olfactory mucosa sampling in COVID-19 patients presenting with persistent loss of smell reveals the presence of virus transcripts and of SARS-CoV-2-infected cells, together with protracted inflammation. Viral persistence in the olfactory epithelium therefore provides a potential mechanism for prolonged or relapsing symptoms of COVID-19, such as loss of smell, which should be considered for optimal medical management and future therapeutic strategies.

neuroscience↗