Biology subjects

Simon-Loriere, E.

Publications and source records attributed to Simon-Loriere, E..

At least 19 recordsLinked to original sources

bioRxiv2026

Non-retroviral Endogenous Viral Element Acts as a Stable Antiviral Regulator Across Mosquito Life Stages and Generations

Endogenous viral elements (EVEs) from non-retroviral RNA viruses are widespread in host genomes, yet their functional significance in vivo remains poorly understood. In mosquitoes, EVEs have been shown to suppress cognate viral replication through the PIWI-interacting RNA (piRNA) pathway. However, how this antiviral activity shapes virus-host dynamics beyond reducing viral replication remains unclear. Here, we established Aedes aegypti mosquito lines naturally infected with cell-fusing agent virus (CFAV) that differ in the presence or absence of a CFAV-derived EVE (CFAV-EVE1). Using this natural virus-host system, we showed that CFAV-EVE1 suppressed viral replication across sexes, tissues, developmental stages, and generations. This antiviral effect is initiated by EVE-derived primary piRNAs, as demonstrated in ovaries and heads. Despite reducing viral load, CFAV-EVE1 conferred no measurable benefits on mosquito survival or reproduction, nor did it eliminate CFAV from the naturally infected population under standard laboratory conditions. However, vertical transmission rates were reduced in EVE-containing mosquitoes and prolonged egg storage further reduced viral prevalence, suggesting that environmental stress may reveal EVE-mediated viral suppression. Together, these findings demonstrate that EVEs function as stable, heritable regulators of persistent virus-host interactions and highlight that ecological context may be critical for fully appreciating their functional significance.

microbiology↗

bioRxiv2026

Temperature-Dependent Replication and Sensitivity to Innate Immunity of Human Coronavirus HKU1

The human coronavirus HKU1, causing common colds and occasionally severe illness, remains largely uncharacterized because it has not been successfully grown on immortalized cells. Here, we identified Caco2 cells overexpressing TMPRSS2, the HKU1 receptor, as being highly permissive to infection. HKU1 replicated efficiently, formed syncytia and released infectious progeny in these cells at 33{degrees}C, the temperature of the nasal cavity, but was attenuated at 37{degrees}C. Viral entry occurred similarly at both temperatures, but subsequent viral RNA synthesis was enhanced at 33{degrees}C. Released virions displayed higher stability at 33{degrees}C. In Caco2 and primary epithelial nasal cells, HKU1 was sensitive to interferons (IFN), but induction of IFN stimulated genes, such as IFN-Induced Transmembrane Proteins (IFITMs), was delayed at 33{degrees}C. Once expressed, IFITMs comparably inhibited HKU1 fusion at both temperatures. In contrast, SARS-CoV-2 robustly replicated at 37{degrees}C. Thus, cellular permissiveness, innate immunity and viral properties collectively explain why HKU1 replicates more efficiently at nasal temperature. Our results highlight temperature-sensitivity disparities between coronaviruses, likely associated to different pathogenic outcomes.

microbiology↗

bioRxiv2026

Phylogenetic analysis of enteroviruses from non-human primates reveals two new species within the genus Enterovirus and inter-species recombination

To date, 15 species have been described within the genus Enterovirus. Previous studies suggested the existence of another species comprising strains isolated from the stool specimens of non-human primates (NHPs) in Central Africa. Moreover, numerous full-length or partial genomic sequences of NHP enteroviruses (EVs) can be found in GenBank without being properly classified. To our knowledge, no comprehensive synthesis of NHP EV data exists, leaving genetic relationships between strains across independent studies unclear. To address these gaps, we sequenced the complete genome of four NHP EVs from our stool collection and conducted an extensive search of NHP EV sequences in GenBank to perform a comprehensive phylogenetic analysis. Our analyses revealed two new species tentatively named Enterovirus mbel and Enterovirus noa, which contain at least 6 and 2 virus types, respectively. We also identified new virus types within the known species EV-J. Phylogenetic analyses strongly suggest interspecies recombination events between NHP EVs in the non-structural region of the genome, challenging the long-held view that recombination is confined within narrowly defined subsets of EVs belonging to the same species. We also performed the first comprehensive comparative analysis of full length human and NHP EV genomes, focusing on GC content, dinucleotide frequencies and codon-usage bias. GC content emerged as the most robust host-associated marker: all NHP-associated virus types within species E. alphacoxsackie and E. betacoxsackie displayed GC % below 47 %, whereas human-derived virus types exhibited GC % above 47 %. Dinucleotide frequency, Effective Number of Codons (ENC) and Relative Synonymous Codon Usage highlighted distinct codon-bias clusters that mirror the phylogenetic relationships between EVs but only partially correlate with their respective hosts of origin. This work enhances our understanding of EVs circulating in NHPs and paves the way for future research aiming at understanding the mechanisms underlying host-adaptation among EVs.

genomics↗

bioRxiv2025

A modified oncolytic measles virus exhibits strong immunotherapeutic potential through RIG-I activation by defective viral genomes

Oncolytic viruses can destroy tumors directly or by activating antitumor immunity, but balancing safety with potent immune stimulation remains challenging. Here, we show that deletion of the measles virus C protein, a key viral antagonist of innate immunity, reprograms the live-attenuated vaccine strain into a RIG-I-driven cancer immunotherapy. The resulting virus, MVdeltaC, accumulates defective viral genomes that activate RIG-I/MAVS signaling and trigger robust type I interferon and pro-inflammatory cytokine responses. MVdeltaC kills tumor cells more rapidly and efficiently than the parental virus and induces hallmarks of immunogenic cell death, including HMGB1 release and dendritic cell maturation. Intratumoral administration in immunocompetent mice bearing syngeneic neuroblastoma induced complete tumor regression in 90% of animals and established long-term antitumor memory. Antitumor responses were dependent on CD8 T and NK cells and were further enhanced by anti-CTLA-4 therapy or CD4 T-cell depletion. Prior measles immunization accelerated tumor clearance, indicating vaccine-boosted responses. MVdeltaC also controlled the growth of human mesothelioma, melanoma, and triple-negative breast cancer xenografts and patient-derived tumors in immunodeficient models. These findings establish MVdeltaC as a clinically ready, broad-spectrum immunotherapeutic that links RIG-I activation through defective viral genome generation to elicit potent and durable antitumor immunity. IMPACT StatementA modified measles virus lacking a viral innate immunity antagonist triggers potent antitumor responses via RIG-I sensing of defective viral genomes, revealing a new strategy for cancer immunotherapy.

immunology↗

bioRxiv2025

Characterization and evolutionary history of novel SARS-CoV-2-related viruses in bats from Cambodia

Circulating bat coronaviruses present a significant pandemic threat, yet our understanding of their genetic diversity and evolutionary dynamics remains limited. Over 3 years, we sampled 1,462 bats in Cambodias Steung Treng province, identifying extensive and diverse coronaviruses co-circulation. Using metatranscriptomic and amplicon sequencing, we generated 33 complete sarbecovirus genomes, revealing novel lineages that cluster into four distinct groups, each associated with different Rhinolophus bat species. Our analysis highlights rapid migration and recombination of sarbecovirus lineages over short distances and timescales. Of note, the receptor-binding domains of two novel viral groups exhibit high similarity to SARS-CoV-2, and pseudovirus assays confirmed the ability of this spike protein to mediate entry into cells expressing human ACE2, suggesting a potential zoonotic risk. The observed genetic diversity underscores the urgent need for continuous surveillance to identify high-risk animal-to-human interfaces and inform pandemic preparedness.

microbiology↗

bioRxiv2025

Identification of a unique TUBB3+ cell population in the tuberculosis granuloma

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a leading cause of mortality worldwide. Granulomas, hallmark structures of TB in the lungs and other infected tissues, are critical sites of host-pathogen interactions, yet their full cellular composition is not completely understood. Here, we identify a previously unrecognized {beta}3-tubulin (TUBB3)-positive cell population within TB granulomas in mice, guinea pigs, non-human primates, and TB patients. TUBB3 is a well-established pan-neuronal marker, yet these TUBB3+ cells are distinct from typical pulmonary resident cells and leukocytes. They exhibit a branched, elongated morphology, which is suggestive of neuron-like features. Intriguingly, their appearance is independent of adaptive immunity and is also observed in viral and fungal infections, but not in asthma. Our findings suggest the existence of a neuro-immune component within granulomas that may influence TB pathogenesis. Further investigation into the origin, function, and signaling pathways of these TUBB3+ cells is required to clarify their identity and potential role in host defense, which could reveal novel therapeutic targets for TB and other pulmonary infections.

immunology↗

bioRxiv2025

Polygenic viral factors enable efficient mosquito-borne transmission of African Zika virus

Zika virus (ZIKV) is a mosquito-borne flavivirus primarily transmitted among humans by Aedes aegypti. Over the past two decades, it has caused significant outbreaks associated with birth defects and neurological disorders. Phylogenetically, ZIKV consists of two main genotypes referred to as the African and Asian lineages, each exhibiting distinct biological properties. African lineage strains are transmitted more efficiently by mosquitoes, but pinpointing the genetic basis of this difference has remained challenging. Here, we address this question by comparing recent African and Asian strains using chimeric viruses, in which segments of the parental genomes are swapped. Our results show that the structural genes from the African strain enhance viral internalization, while the non-structural genes improve genome replication and infectious particle production in mosquito cells. In vivo mosquito transmission is most significantly influenced by the structural genes, although no single viral gene alone determines this effect. Additionally, we develop a stochastic model of in vivo viral dynamics in mosquitoes that mirrors the observed patterns, suggesting that the primary difference between the African and Asian strains lies in their ability to traverse the mosquito salivary glands. Overall, our findings suggest that the polygenic nature of ZIKV transmissibility has prevented Asian lineage strains from achieving the same epidemic potential as African lineage strains, underscoring the importance of lineage-specific adaptive landscapes in shaping ZIKV evolution and emergence.

microbiology↗

bioRxiv2024

Antiviral activity of Tecovirimat against Mpox virus clades 1a, 1b, 2a and 2b

The recent Mpox virus (MPXV) outbreak was caused by a novel and more pathogenic clade 1b virus. We compared the antiviral efficacy of Tecovirimat in cell culture, against the two ancestral clades 1a and 2a, the clade 2b that circulated in 2022, and the recent clade 1b virus. We report that Tecovirimat similarly inhibits the replication of all four MPXV clades, at nanomolar concentrations (nM). Our results suggest that Tecovirimat remains a therapeutic option against the latest clade 1b virus.

microbiology↗

bioRxiv2024

Development of a competition assay to assess the in vitro fitness of dengue virus serotypes using an optimized serotype-specific qRT-PCR

BackgroundComparing the in vitro fitness of dengue virus (DENV) isolates is a pivotal approach to assess the contribution of DENV strains replicative fitness to epidemiological contexts, including serotype replacements. Competition assays are the gold standard to compare the in vitro replicative fitness of viral strains. Implementing competition assays between DENV serotypes requires an experimental setup and an appropriate read-out to quantify the viral progeny of strains belonging to different serotypes. ResultsIn the current study, we optimized an existing serotyping qRT-PCR by adapting primer/probe design and multiplexing the serotype-specific qRT-PCR reactions, allowing to accurately detect and quantify all four DENV serotypes. The qRT-PCR was specific, had a limit of detection of at least 5.08x101, 5.16x101, 7.14x101 and 1.36 x101 genome copies/{micro}L, an efficiency of 1.993, 1.975, 1.902, 1.898 and a linearity (R{superscript 2}) of 0.99975, 0.99975, 0.9985, 0.99965 for DENV-1, -2, -3 and -4 respectively. Challenge of this multiplex serotype-specific qRT-PCR on mixes of viral supernatants containing known concentrations of strains from two serotypes evidenced an accurate quantification of the amount of genome copies of each serotype. We next developed an in vitro assay to compare the replicative fitness of two DENV serotypes in the human hepatic cell line HuH7: quantification of the viral progeny of each serotype in the inoculum and the supernatant using the serotype-specific multiplex qRT-PCR unveiled an enrichment of the supernatant in DENV-1 genome copies, uncovering the enhanced replicative fitness of this DENV-1 isolate. ConclusionsThis optimized qRT-PCR combined to a relevant cellular model allowed to accurately quantify the viral progeny of two DENV strains belonging to two different serotypes in a competition assay, allowing to determine which strain had a replicative advantage. This reliable experimental setup is adaptable to the comparative study of the replicative fitness of any DENV serotypes.

microbiology↗

bioRxiv2024

Escape of SARS-CoV-2 variants KP1.1, LB.1 and KP3.3 from approved monoclonal antibodies

First-generation anti-SARS-CoV-2 monoclonal antibodies (mAbs) used for prophylaxis or therapeutic purposes in immunocompromised patients have been withdrawn because of the emergence of resistant Omicron variants. In 2024, two novel mAbs, Pemivibart and Sipavibart, have been approved by health authorities, but their activity against contemporary JN.1 sublineages is poorly characterized. We isolated authentic JN.1.1, KP1.1, LB.1 and KP3.3 viruses and evaluated their sensitivity to neutralization by these mAbs in two target cell lines. Compared to ancestral strains, Pemivibart remained moderately active against JN.1 sub-variants, with a strong increase of 50% Inhibitory Concentration (IC50), reaching up to 3 to 15 g/ml for KP3.3. Sipavibart neutralized JN.1.1 but lost antiviral efficacy against KP1.1, LB.1 and KP3.3. Our results highlight the need for a close clinical monitoring of Pemivibart and raise concerns about the clinical efficacy of Sipavibart.

immunology↗

bioRxiv2024

B cell maturation restored ancestral germlines to control Omicron BA.2.86

The unceasing interplay between SARS-CoV-2 and the human immune system has led to a continuous maturation of the virus and B cell response providing an opportunity to track their evolution in real time. We longitudinally analyzed the functional activity of almost 1,000 neutralizing human monoclonal antibodies (nAbs) isolated from vaccinated people, and from individuals with hybrid and super hybrid immunity (SH), developed after three mRNA vaccine doses and two breakthrough infections. The most potent neutralization and Fc functions against highly mutated variants, including BA.2.86, were found in the SH cohort. Despite different priming, epitope mapping revealed a convergent maturation of the functional antibody response. Neutralization was mainly driven by Class 1/2 nAbs while Fc functions were induced by Class 3/4 antibodies. Remarkably, broad neutralization was mediated by restored IGHV3-53/3-66 B cell germlines which, after heterogenous exposure to SARS-CoV-2 S proteins, increased their level of somatic hypermutations. Our study shows the resilience of the human immune system which restored previously expanded germlines and activated naive B cells to broaden the antibody repertoire of antibodies to control future SARS-CoV-2 variants.

immunology↗

bioRxiv2023

Neutralisation of SARS-CoV-2 Omicron subvariants BA.2.86 and EG.5.1 by antibodies induced by earlier infection or vaccination

Highly mutated SARS-CoV-2 Omicron subvariant BA.2.86 emerged in July 2023. We investigated the neutralisation of isolated virus by antibodies induced by earlier infection or vaccination. The neutralisation titres for BA.2.86 were comparable to those for XBB.1 and EG.5.1, by antibodies induced by XBB.1.5 or BA.4/5 breakthrough infection or BA.4/5 vaccination.

immunology↗

bioRxiv2023

High fusion and cytopathy of SARS-CoV-2 variant B.1.640.1

SARS-CoV-2 variants with undetermined properties have emerged intermittently throughout the COVID-19 pandemic. Some variants possess unique phenotypes and mutations which allow further characterization of viral evolution and spike functions. Around 1100 cases of the B.1.640.1 variant were reported in Africa and Europe between 2021 and 2022, before the expansion of Omicron. Here, we analyzed the biological properties of a B.1.640.1 isolate and its spike. Compared to the ancestral spike, B.1.640.1 carried 14 amino acid substitutions and deletions. B.1.640.1 escaped binding by some anti-NTD and -RBD monoclonal antibodies, and neutralization by sera from convalescent and vaccinated individuals. In cell lines, infection generated large syncytia and a high cytopathic effect. In primary airway cells, B.1.640.1 replicated less than Omicron BA.1 and triggered more syncytia and cell death than other variants. The B.1.640.1 spike was highly fusogenic when expressed alone. This was mediated by two poorly characterized and infrequent mutations located in the spike S2 domain, T859N and D936H. Altogether, our results highlight the cytopathy of a hyper-fusogenic SARS-CoV-2 variant, supplanted upon the emergence of Omicron BA.1. ImportanceOur results highlight the plasticity of SARS-CoV-2 spike to generate highly fusogenic and cytopathic strains with the causative mutations being uncharacterized in previous variants. We describe mechanisms regulating the formation of syncytia and the subsequent consequences in cell lines and a primary culture model, which are poorly understood.

microbiology↗

bioRxiv2023

Investigations on SARS-CoV-2 and other coronaviruses in mink farms in France at the end of the first year of COVID-19 pandemic

Soon after the beginning of the COVID-19 pandemic in early 2020, the Betacoronavirus SARS-CoV-2 infection of several mink farms breeding American minks (Neovison vison) for fur was detected in several countries of Europe. The risk of a new reservoir formation and of a reverse zoonosis from minks was then a major concern. The aim of this study was to investigate the four French mink farms for the circulation of SARS-CoV-2 at the end of 2020. The investigations took place during the slaughtering period thus facilitating different types of sampling (swabs and blood). In one of the four mink farms, 96.6% of serum samples were positive in SARS-CoV-2 ELISA coated with purified N protein recombinant antigen and 54 out of 162 (33%) pharyngo-tracheal swabs were positive by RT-qPCR. The genetic variability among 12 SARS-CoV-2 genomes sequenced in this farm indicated the co-circulation of several lineages at the time of sampling. All SARS-CoV-2 genomes detected were nested within the 20A clade (Nextclade), together with SARS-CoV-2 genomes from humans sampled at the same period. The percentage of SARS-CoV-2 seropositivity by ELISA varied between 0.5 and 1.2% in the three other farms. Interestingly, among these three farms, 11 pharyngo-tracheal swabs and 3 fecal pools from two farms were positive by end-point RT-PCR for an Alphacoronavirus highly similar to a mink coronavirus sequence observed in Danish farms in 2015. In addition, a mink Caliciviridae was identified in one of the two positive farms for Alphacoronavirus. The clinical impact of these unapparent viral infections is not known. The co-infection of SARS-CoV-2 with other viruses in mink farms could contribute to explain the diversity of clinical symptoms noted in different infected farms in Europe. In addition, the co-circulation of an Alphacoronavirus and SARS-CoV-2 within a mink farm would increase potentially the risk of viral recombination between alpha and betacoronaviruses already suggested in wild and domestic animals, as well as in humans. Author summaryFrance is not a country of major mink fur production. Following the SARS-CoV-2 contamination of mink farms in Denmark and the Netherlands, the question arose for the four French farms. The investigation conducted at the same time in the four farms revealed the contamination of one of them by a variant different from the one circulating at the same time in Denmark and the Netherlands mink farms. Investigation of three other farms free of SARS-CoV-2 contamination revealed the circulation of other viruses including a mink Alphacoronavirus and Caliciviridae, which could modify the symptomatology of SARS-CoV-2 infection in minks.

microbiology↗

bioRxiv2023

APOBEC3F is the main source of editing identified during the 2022 outbreak of human monkeypox virus

On May 6, 2022, a powerful outbreak of monkeypox virus (MPXV) had been reported outside of Africa, with many continuing new cases being reported around the world. Analysis of mutations among the two different lineages present in the 2021 and 2022 outbreaks revealed the presence of G->A mutations occurring in the 5GpA context, indicative of APOBEC3 cytosine deaminase activity. By using a sensitive PCR (3D-PCR) method allowing differential amplification of AT-rich DNA, we demonstrate that G->A hypermutated MPXV genomes can be recovered experimentally from APOBEC3 transfection followed by MPXV infection. Here, among the 7 human APOBEC3 cytidine deaminases (A3A-A3C, A3DE, A3F-A3H), only APOBEC3F was capable of extensively deaminating cytidine residues in MPXV genomes. Hyperedited genomes were also recovered in ~42% of analyzed patients, indicating that editing is part of the natural cycle of MPXV infection. Moreover, we demonstrate that substantial repair of these mutations occurs. Upon selection, corrected G->A mutations escaping drift loss contribute to the MPXV evolution observed in the current epidemics. Thus, stochastic or transient overexpression of APOBEC3F gene exposes the MPXV genome to a broad spectrum of mutations that may be modeling the mutational landscape after multiple cycles of viral replication.

microbiology↗

bioRxiv2022

Enhanced neutralization escape to therapeutic monoclonal antibodies by SARS-CoV-2 Omicron sub-lineages

The landscape of SARS-CoV-2 variants dramatically diversified with the simultaneous appearance of multiple sub-variants originating from BA.2, BA.4 and BA.5 Omicron sub-lineages. They harbor a specific set of mutations in the spike that can make them more evasive to therapeutic monoclonal antibodies. In this study, we compared the neutralizing potential of monoclonal antibodies against the Omicron BA.2.75.2, BQ.1, BQ.1.1 and XBB variants, with a pre-Omicron Delta variant as a reference. Sotrovimab retains some activity against BA.2.75.2, BQ.1 and XBB as it did against BA.2/BA.5, but is less active against BQ.1.1. Within the Evusheld/AZD7442 cocktail, Cilgavimab lost all activity against all subvariants studied, resulting in loss of Evusheld activity. Finally, Bebtelovimab, while still active against BA.2.75, also lost all neutralizing activity against BQ.1, BQ.1.1 and XBB variants.

microbiology↗

bioRxiv2022

Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies

Convergent evolution of SARS-CoV-2 Omicron BA.2, BA.4 and BA.5 lineages has led to the emergence of several new subvariants, including BA.2.75.2, BA.4.6. and BQ.1.1. The subvariants BA.2.75.2 and BQ.1.1 are expected to become predominant in many countries in November 2022. They carry an additional and often redundant set of mutations in the spike, likely responsible for increased transmissibility and immune evasion. Here, we established a viral amplification procedure to easily isolate Omicron strains. We examined their sensitivity to 6 therapeutic monoclonal antibodies (mAbs) and to 72 sera from Pfizer BNT162b2-vaccinated individuals, with or without BA.1/BA.2 or BA.5 breakthrough infection. Ronapreve (Casirivimab and Imdevimab) and Evusheld (Cilgavimab and Tixagevimab) lost any antiviral efficacy against BA.2.75.2 and BQ.1.1, whereas Xevudy (Sotrovimab) remained weakly active. BQ.1.1 was also resistant to Bebtelovimab. Neutralizing titers in triply vaccinated individuals were low to undetectable against BQ.1.1 and BA.2.75.2, 4 months after boosting. A BA.1/BA.2 breakthrough infection increased these titers, which remained about 18-fold lower against BA.2.75.2 and BQ.1.1, than against BA.1. Reciprocally, a BA.5 breakthrough infection increased more efficiently neutralization against BA.5 and BQ.1.1 than against BA.2.75.2. Thus, the evolution trajectory of novel Omicron subvariants facilitated their spread in immunized populations and raises concerns about the efficacy of most currently available mAbs.

microbiology↗

bioRxiv2022

SARS-CoV-2 infection in domestic rats after transmission from their infected owner

We report the transmission of SARS-CoV-2 Omicron variant from a COVID-19 symptomatic individual to two domestic rats, one of which developed severe symptoms. Omicron carries several mutations which permit rodent infection. This report demonstrates that pet, and likely wild, rodents could therefore contribute to SARS-CoV-2 spread and evolution.

microbiology↗