Biology subjects

Dubrulle, J.

Publications and source records attributed to Dubrulle, J..

17 recordsLinked to original sources

bioRxiv2026

Urban waterfowl harbour geographically connected viral communities across Aotearoa New Zealand

Urban waterfowl are important natural reservoirs of viruses that can affect wildlife, livestock and human health, yet the diversity and spatial distribution of these viral communities remain poorly understood. Here, we characterised the faecal viromes of urban waterfowl sampled from 13 locations across the length of Aotearoa (New Zealand). We identified 96 avian viruses (50 species) spanning nine viral families, including 33 previously undescribed viruses. Picornaviruses were the most widespread viral group, while several viruses were closely related to those previously identified in Australian waterfowl, indicating that some viral lineages are likely distributed across the broader Australasian region. Despite sampling locations spanning more than 1,500 km, virome composition exhibited little evidence of geographic structure, with little difference in viral diversity or community composition between sampling locations. Network analyses similarly demonstrated extensive sharing of virus species among sampling locations, indicating little geographic structuring of virome composition among urban waterfowl. In addition, we recovered the complete genome of a low-pathogenic A(H3N8) influenza A virus from mallards (Anas platyrhynchos) in the most southern region of Aotearoa. These findings reveal extensive viral diversity and widespread connectivity among urban waterfowl, providing new insights into viral ecology and the potential for widespread virus distribution across Aotearoa.

microbiology↗

bioRxiv2026

Antitoxin-induced auto-phosphorylation neutralizes the nucleotidyltransferase toxin AbiEii from Streptococcus agalactiae to safeguard global translation

Nucleotidyltransferases (NTases) control diverse physiological processes, including DNA replication and repair, antibiotic resistance, and RNA modification. The Streptococcus agalactiae abortive infection family toxin, AbiEii, belongs to the DUF1814 superfamily of NTases and blocks bacterial growth through an as yet unknown mechanism. Antitoxin AbiEi has been reported to antagonize AbiEii as part of a Type IV toxin-antitoxin system. Here, we demonstrate through structural, biochemical, and biophysical studies that AbiEi binds to AbiEii to form a stable toxin-antitoxin complex in solution. Antitoxin binding ultimately leads to AbiEii auto-phosphorylation and an abolition of NTase activity. These data reclassify AbiE systems as Type VII toxin-antitoxin systems. Toxin phosphorylation appears to be a dynamic and reversible process, and we show that the sole serine/threonine phosphatase SaSTP of S. agalactiae can efficiently dephosphorylate AbiEii in vitro. Mutagenesis studies and functional assays indicate that a widespread mechanism of toxin auto-phosphorylation accounts for AbiEii neutralization, further supporting recent hypotheses outlining control of homologous MenAT toxin-antitoxin systems from Mycobacterium tuberculosis.

molecular biology↗

bioRxiv2025

Foraging ecology drives viral community structure in New Zealand's aquatic birds

Wild migratory birds play a major role in the global spread of viruses, yet the diversity, host range and transmission patterns of viruses harboured by migratory species in Aotearoa/New Zealand remain largely unknown. This knowledge gap is critical given New Zealands position along major migratory flyways spanning Oceania, Antarctica and east Asia, where understanding viral diversity is key to assessing the risk of viral introductions such as highly pathogenic avian influenza virus and viral dispersal across these regions. To address this, we conducted the first large-scale metatranscriptomic survey of wild birds from New Zealand and its subantarctic islands, collecting 1,348 samples from 31 host species spanning four avian orders. We identified 118 avian viruses from 17 families, including 107 novel species, greatly expanding our knowledge of avian viral diversity. Viral communities differed significantly by host order and foraging behaviour, with scavenger birds harbouring more diverse viromes than non-scavengers. Although no HPAI subtypes were detected, we recovered a low-pathogenic avian influenza A/H1N9 virus from red knots (Calidris canutus) and a divergent tobanivirus from Auckland Island teal (Anas aucklandica), the first putative avian member of the Tobaniviridae. Notably, we detected 12 mammalian-associated viruses, primarily in scavenger birds, including Hedgehog hepatovirus, Rabbit haemorrhagic disease virus 2, and sea lion astroviruses, with mammalian host reads confirming their dietary origin. This study establishes the first virome baseline for New Zealands migratory birds, highlighting the ecological role of foraging in shaping viral communities and improving regional preparedness for HPAI and other emerging avian pathogens.

microbiology↗

bioRxiv2025

Viral surveillance of invasive mammals in New Zealand reveals unique viral lineages reflecting their introduction history

Introduced mammalian species in Aotearoa New Zealand pose significant ecological risks and may serve as reservoirs for novel or emerging infectious diseases. In this study, we present the first metatranscriptomic survey of viruses in five introduced mammals: ferrets (Mustela furo), stoats (Mustela erminea), weasels (Mustela nivalis), brushtail possums (Trichosurus vulpecula), and European hedgehogs (Erinaceus europaeus), sampled across both the North and South Islands. Through total RNA sequencing, we identified 11 mammalian-infecting viruses spanning eight viral families, including four novel virus species: Ferret mastadenovirus, Possum astrovirus, Ferret pestivirus, and Weasel jeilongvirus. Whole genomes were recovered for six of these viruses, enabling detailed phylogenetic analysis. Notably, we observed strong global geographic clustering in both Wobbly possum disease virus and Ferret hepatitis E virus, suggesting localized viral evolution following the introduction of their hosts into New Zealand. In addition, the detection of Human rotavirus A in hedgehogs highlights the possibility of reverse zoonotic transmission. Together, these findings broaden our understanding of the viral diversity harboured by New Zealands introduced mammals and provide a critical foundation for future biocontrol and disease surveillance ehorts. IMPORTANCEIntroduced mammals in Aotearoa New Zealand not only threaten native biodiversity through predation and competition, but also represent a largely overlooked source of infectious disease risk. Viruses circulating in these species may spill over into native wildlife, livestock, or even humans, while human viruses can also establish in introduced animals and create new reservoirs. Understanding which viruses are present, and how they evolve in isolated host populations, is critical for anticipating future disease outbreaks, improving biosecurity, and guiding wildlife management strategies. This work provides foundational knowledge that links ecology, conservation, and health, highlighting the need to consider pathogens as part of the broader impact of invasive species.

microbiology↗

bioRxiv2025

Genital herpes shedding episodes associate with alterations in the spatial organization and activation of mucosal immune cells

Herpes Simplex Virus 2 (HSV-2) infection results in variable rates of local viral shedding in anogenital skin. The impact of episodic viral exposures on immune cells in adjacent mucosal tissues, including the genital tract, is unknown. However, any immune responses at this site could impact protective mucosal immunity, tissue homeostasis, and adverse health outcomes. To investigate the impact of HSV-2 on cervicovaginal tract immunity, we applied flow cytometry, immunofluorescent imaging, analysis of soluble immune factors, and spatial transcriptomics to cervicovaginal tissue and blood samples provided by a total of 232 HSV-2 seropositive and seronegative participants, with genital HSV-2 shedding evaluated at the time of biopsy. This unique dataset was used to define and spatially map immune cell subsets and localized gene expression via spatial transcriptomics. HSV-2 seropositivity alone was associated with minimal differences in cervicovaginal and circulating T cell phenotypes. However, the vaginal mucosa during active HSV-2 shedding was associated with alterations in T cell, macrophage, and dendritic cell localization and gene expression consistent with increased immune surveillance, with immune activating and suppressing signals potentially reinforcing mucosal tissue homeostasis. SummaryIn context of episodic HSV-2 shedding, immune cells mobilize and co-localize in the vaginal epithelium, expressing cytotoxic and inflammatory genes and immunoregulatory genes that collectively may promote tissue homeostasis in settings of episodic viral shedding to limit damage.

immunology↗

bioRxiv2024

Avian influenza virus surveillance across New Zealand and its subantarctic islands detects H1N9 in migratory shorebirds, but not 2.3.4.4b HPAI H5N1

Highly pathogenic avian influenza (HPAI) virus has never been detected in New Zealand. The potential impact of this virus on New Zealands wild birds would be catastrophic. To expand our knowledge of avian influenza viruses across New Zealand, we sampled wild aquatic birds from New Zealand, its outer islands and its subantarctic territories. Metatranscriptomic analysis of 700 individuals spanning 33 species revealed no detection of HPAI during the annual 2023-2024 migration. A single detection of H1N9 in red knots (Calidris canutus) was noted. This study provides a baseline for expanding avian influenza virus monitoring in New Zealand.

microbiology↗

bioRxiv2024

Bacterial vaginosis-driven changes in vaginal T cell phenotypes and their implications for HIV susceptibility

Bacterial vaginosis (BV) is a dysbiosis of the vaginal microbiome that is prevalent among reproductive-age females worldwide. Adverse health outcomes associated with BV include an increased risk of sexually-acquired HIV, yet the immunological mechanisms underlying this association are not well understood. To investigate BV-driven changes to cervicovaginal tract (CVT) and circulating T cell phenotypes, participants with or without BV provided vaginal tract (VT) and ectocervical (CX) tissue biopsies and PBMC samples. High-parameter flow cytometry revealed an increased frequency of cervical conventional CD4+ T cells (Tconv) expressing CCR5. However, we found no difference in number of CD3+CD4+CCR5+ cells in the CX or VT of BV+ vs BV- individuals, suggesting that BV-driven increased HIV susceptibility may not be solely attributed to increased CVT HIV target cell abundance. Flow cytometry also revealed that individuals with BV have an increased frequency of dysfunctional CX and VT CD39+ Tconv and CX tissue-resident CD69+CD103+ Tconv, reported to be implicated in HIV acquisition risk and replication. Many soluble immune factor differences in the CVT further support that BV elicits diverse and complex CVT immune alterations. Our comprehensive analysis expands on potential immunological mechanisms that may underlie the adverse health outcomes associated with BV including increased HIV susceptibility.

immunology↗

bioRxiv2024

Viromes of Antarctic fish resembles the diversity found at lower latitudes

Antarctica harbours some of the most isolated and extreme environments on Earth, concealing a largely unexplored and unique component of the global animal virosphere. To understand the diversity and evolutionary histories of viruses in these polar species we determined the viromes of 11 Antarctic fish species with 248 samples collected from the Ross Sea region spanning the Perciformes, Gadiformes, and Scorpaeniformes orders. The continents shift southward and cooling temperatures over 20 million years ago led to a reduction in biodiversity and subsequent radiation of some marine fauna, such as the notothenioid fishes. Despite decreased host species richness in polar regions, we revealed a surprisingly complex virome diversity in Ross Sea fish, with the types and numbers of viruses per host species and individuals sampled comparable to that of fish in warmer marine environments with higher host community diversity. We also observed a higher number of closely related viruses likely representing instances of recent and historic host-switching events among Perciformes (all notothenioids) than in the Gadiformes, suggesting that rapid speciation events within this order generated closely related host species with few genetic barriers to cross-species transmission. Additionally, we identified novel genomic variation in an arenavirus with a split nucleoprotein sequence containing a stable helical structure, indicating potential adaptation of viral proteins to extreme temperatures. These findings enhance our understanding of virus evolution and virus-host interactions in response to environmental shifts, especially in less diverse ecosystems more vulnerable to the impacts of anthropogenic and climate changes.

microbiology↗

bioRxiv2023

Atg8-LC3 controls systemic nutrient surplus signaling from flies to humans.

Organisms experience constant nutritional flux, and homeostatic mechanisms evolved to operate at the nexus of extreme nutritional states - scarcity and surplus. Thus, we surmised that decoding bidirectional molecular switches that operate at the interface of scarcity response and surplus signaling will enable the development of strategies to treat disorders that arise from nutrient imbalance states. Adipocytes secrete leptin, an interleukin protein, which signals nutrient surplus to the central brain to regulate feeding and energy expenditure. We report that Atg8-LC3-family proteins, best known for their role in autophagy, are required for leptin secretion in Drosophila and human adipocytes. Atg8-LC3 genetic knockdown and point mutations to the Atg8-LC3 interaction motif (AIM/LIR) of leptin, and its functional ortholog in Drosophila, Upd2, disrupt adipokine secretion and increase adipokine retention in human and fly cells. At an organismal level, Atg8-driven Upd2 retention increases organismal resilience to nutrient extremes by rewiring the transcriptome, organismal feeding behavior, and hunger response. Comparative proteomic analyses reveal that LC3 directs leptin to an exosome secretory pathway. We use genetic knockdown in primary human adipocytes to establish that LC3 is required for leptin secretion in a physiologically relevant mammalian system. Hence, we uncover a previously unknown and evolutionarily conserved role for Atg8-LC3 in promoting adipocyte-brain nutrient surplus signaling. We propose that Atg8-LC3s bidirectional role in nutrient sensing-conveying nutrient surplus and responding to nutrient deprivation-enables organisms to manage nutrient flux effectively.

physiology↗

bioRxiv2023

Single molecule visualization of native centromeric nucleosome formation reveals coordinated deposition by kinetochore proteins and centromere DNA sequence

Eukaryotic chromosome segregation requires the kinetochore, a megadalton-sized machine that forms on specialized centromeric chromatin containing CENP-A, a histone H3 variant. CENP-A deposition requires a chaperone protein HJURP that targets it to the centromere, but it has remained unclear whether HJURP has additional functions beyond CENP-A targeting and why high AT DNA content, which disfavors nucleosome assembly, is widely conserved at centromeres. To overcome the difficulties of studying nucleosome formation in vivo, we developed a microscopy assay that enables direct observation of de novo centromeric nucleosome recruitment and maintenance with single molecule resolution. Using this assay, we discover that CENP-A can arrive at centromeres without its dedicated centromere-specific chaperone HJURP, but stable incorporation depends on HJURP and additional DNA-binding proteins of the inner kinetochore. We also show that homopolymer AT runs in the yeast centromeres are essential for efficient CENP-A deposition. Together, our findings reveal requirements for stable nucleosome formation and provide a foundation for further studies of the assembly and dynamics of native kinetochore complexes.

biophysics↗

bioRxiv2022

Single-cell profiling uncovers a Muc4-expressing metaplastic gastric cell type sustained by Helicobacter pylori-specific inflammation

AbstractMechanisms for Helicobacter pylori (Hp)-driven stomach cancer are not fully understood. In a transgenic mouse model of gastric preneoplasia, concomitant Hp infection and induction of constitutively active KRAS (Hp+KRAS+) alters metaplasia phenotypes and elicits greater inflammation than either perturbation alone. Gastric single-cell RNA-seq showed that Hp+KRAS+ mice had a large population of metaplastic pit cells that expressed the intestinal mucin Muc4 and the growth factor amphiregulin. Metaplastic pit cells were associated with macrophage and T cell inflammation and prevented by gastric immunosuppression. Lineage tracing showed that Muc4 was not dependent on cell-intrinsic KRAS activity, and lineage-derived cells had a limited propensity for growth as organoids, demonstrating that metaplastic pit cells are largely not self- renewing. Finally, MUC4 expression was significantly associated with proliferation in human gastric cancer samples. These studies identify an Hp-associated metaplastic pit cell lineage, also found in human gastric cancer tissues, whose expansion is driven by Hp-dependent inflammation. Statement of SignificanceUsing a mouse model, we have delineated metaplastic pit cells as a pre-cancerous cell type whose expansion requires H. pylori-driven inflammation. In humans, metaplastic pit cells show enhanced proliferation as well as enrichment in precancer and early cancer tissues, highlighting an early step in the gastric metaplasia to cancer cascade.

microbiology↗

bioRxiv2022

Focal adhesion assembly requires phosphorylation signaling

Integrin-mediated cell attachment rapidly induces tyrosine kinase signaling. Despite years of research, the role of this signaling in integrin activation and focal adhesion assembly is unclear. We provide evidence that the Src-family kinase (SFK) substrate Cas (Crk-associated substrate, p130Cas, BCAR1) is phosphorylated, and associated with its effectors, Crk/CrkL, in clusters that are precursors of focal adhesions. The initial phospho-Cas clusters contain integrin {beta}1 in its inactive, bent closed, conformation. Later, phospho-Cas and total Cas levels decrease as integrin {beta}1 is activated and core focal adhesion proteins including vinculin, talin, kindlin and paxillin are recruited. Cas is required for cell spreading and focal adhesion assembly in epithelial and fibroblast cells on collagen and fibronectin. Cas cluster formation requires Cas, Crk/CrkL, SFKs and Rac1 but not vinculin. Rac1 provides positive feedback onto Cas through reactive oxygen, opposed by negative feedback from the ubiquitin proteasome system. The results suggest a two-step model for focal adhesion assembly in which clusters of phospho-Cas, effectors and inactive integrin {beta}1 grow through positive feedback prior to integrin activation and recruitment of core focal adhesion proteins.

cell biology↗

bioRxiv2022

A novel gyrovirus associated with a fatal respiratory disease in yellow-eyed penguin (Megadyptes antipodes) chicks

Yellow-eyed penguins (Megadyptes antipodes), or hoiho in te reo M[a]ori, are predicted to become extinct on mainland Aotearoa New Zealand in the next few decades, with infectious disease a significant contributor to their decline. A recent disease phenomenon termed respiratory distress syndrome (RDS) causing lung pathology has been identified in very young chicks. To date, no causative pathogens for RDS have been identified. In 2020 and 2021, the number of chick deaths from suspected RDS increased four- and five-fold, respectively, with a mortality rate of >90%. Here, we aimed to identify possible pathogens responsible for RDS disease impacting yelloweyed penguins. Total RNA was extracted from tissue samples collected during post-mortem of 43 chicks and subject to metatranscriptomic sequencing. From these data we identified a novel and highly abundant gyrovirus in 80% of tissue samples. This virus exhibited only 41% amino acid identity within VP1 to its closest relative, Gyrovirus 8, discovered in a diseased seabird. No other exogenous viral transcripts, nor pathogenic bacterial, protozoal and fungal organisms, were identified in these tissues. Due to the high relative abundance of viral reads, it is likely that this novel gyrovirus is associated with RDS in yellow-eyed penguin chicks. Author SummaryNew Zealands population of yellow-eyed penguins, also called hoiho, are predicted to become extinct in the next 20-30 years, with disease a major factor contributing to their decline. A new disease, causing fluid and bleeding into the lungs, was initially identified in 2019 in very young chicks. It was characterised as causing respiratory distress with a mortality of >90% usually within the first week of life. To date, no causative pathogens of the disease have been identified. We aimed to identify possible pathogens responsible for respiratory disease in these penguin chicks. A metatranscriptomic survey of dead chicks identified a novel and highly abundant gyrovirus present in diseased tissue, with closely related viruses causing disease in other avian hosts. It is, therefore, highly likely that this novel gyrovirus is associated with respiratory disease in these chicks. This finding offers the potential to increase the success of disease management in the critically endangered yellow-eyed penguin and possibly other at-risk penguin species. The potential to lessen mortality and slow the decline of the species is essential in protecting the biodiversity of New Zealands fauna and flora.

microbiology↗

bioRxiv2022

Cell wound repair requires the coordinated action of linear and branched actin nucleation factors

Cells are subjected to a barrage of daily insults that often lead to its cortex being ripped open and requiring immediate repair. An important component of the cell s repair response is the formation of an actomyosin ring at the wound periphery to mediate its closure. Inhibition of linear actin nucleation factors and myosin result in a disrupted contractile apparatus and delayed wound closure. Here we show that branched actin nucleators function as a scaffold to assemble and maintain this contractile actomyosin cable. Removing branched actin leads to the formation of smaller circular actin-myosin structures at the cell cortex and slow wound closure. Removing linear and branched actin results in failed wound closure. Surprisingly, removal of branched actin and myosin results in the formation of parallel linear actin filaments that undergo a chiral swirling movement to close the wound. These results provide insight into actin organization in contractile actomyosin rings and uncover a new mechanism of wound closure. SummaryHui et al. find that branched actin is required during cell wound repair to serve as a scaffold to anchor the contractile actomyosin cable at the wound periphery. Inhibition of branched actin and myosin results in parallel linear filaments that swirl to close the wound, uncovering a new mechanism for cell wound repair.

cell biology↗

bioRxiv2021

Fat Body Phospholipid State Dictates Hunger Driven Feeding Behavior

Diet-induced obesity (DIO) leads to dysfunctional feeding behavior. However, the precise molecular nodes underlying diet-induced dysregulation of satiety sensing and feeding motivation are poorly understood. The fruit fly is a simple genetic model system yet displays significant evolutionary conservation to mammalian nutrient sensing and energy balance. Using a longitudinal high sugar regime in Drosophila, we sought to address how lipid alteration in fat cells alters feeding behavior. We find that prolonged exposure to HSD degrades the hunger-driven feeding (HDF) response. Lipidomics analysis reveals that longitudinal exposure to HSD significantly alters whole body phospholipid profiles. By performing a systematic screen for phospholipid enzymes, we identify Pect as a critical regulator of hunger-driven feeding. Pect is a rate-limiting enzyme in the phosphatidylethanolamine (PE) biosynthesis pathway and the fly ortholog of human PCYT2. We show that disrupting Pect only in the fat body causes insulin-resistant phenotypes and a loss of hunger-driven feeding. Excitingly, we find that overexpression of Pect restores HSD-induced loss of hunger-driven feeding response. Strikingly human studies have noted a correlation between PCYT2/Pect levels and clinical obesity. Now, our unbiased studies in Drosophila provide specific genetic evidence for Pect in maintaining nutrient sensing during DIO. Our study provides novel insights into the role of phospholipids in interorgan communication of nutrient status. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=193 SRC="FIGDIR/small/472854v4_ufigA1.gif" ALT="Figure 1"> View larger version (66K): org.highwire.dtl.DTLVardef@1ecf3eorg.highwire.dtl.DTLVardef@b800f2org.highwire.dtl.DTLVardef@461a7eorg.highwire.dtl.DTLVardef@75651c_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

bioRxiv2020

Helicobacter pylori accelerates KRAS-dependent gastric dysplasia

More than 80% of gastric cancer is attributable to stomach infection with Helicobacter pylori (Hp), even though the bacterium is not always present at time of diagnosis. Infection is thought to lead to cancer by promoting the accumulation of oncogenic mutations downstream of inflammation; once oncogenic pathways become activated, infection may become dispensable for cancer development. Gastric preneoplastic progression involves sequential changes to the tissue, including loss of parietal cells, spasmolytic polypeptide-expressing metaplasia (SPEM), intestinal metaplasia (IM) and dysplasia. In mice, active KRAS expression recapitulates these tissue changes in the absence of Hp infection. This model provides an experimental system to investigate whether Hp infection has additional roles in preneoplastic progression, beyond initiating inflammation. Mice were assessed by evaluating tissue histology, gene expression changes, the immune cell repertoire, and expression of metaplasia and dysplasia markers. Compared to Hp-/KRAS+ mice, Hp+/KRAS+ mice had i) severe T cell infiltration and altered macrophage polarization; ii) altered expression of metaplasia markers, including increased expression of CD44v9 (SPEM) and decreased expression of TFF3 (IM); iii) more dysplastic (TROP2+) glands; and iv) greater proliferation of metaplastic and dysplastic glands. Hp was able to persistently colonize the stomach during the onset of these tissue changes, and eradication of Hp with antibiotics prevented metaplastic, dysplastic and proliferation marker changes. Collectively, these results suggest that gastric preneoplastic progression differs between Hp+ and Hp-cases, and that sustained Hp infection can promote the later stages of gastric preneoplastic progression, in addition to its established role in initiating chronic inflammation.

cancer biology↗

bioRxiv2018

Chronic starvation induces non-canonical pro-death stress granules

Stress granules (SGs) assemble under stress-induced conditions that inhibit protein synthesis, including eIF2 phosphorylation, inhibition of the RNA helicase eIF4a, or inactivation of mTORC1. Classically defined SGs are composed of translation initiation factors, 40S ribosomes, RNA binding proteins, and poly(A)+ mRNAs, and as such represent an important compartment for storage of mRNAs and regulation of their translation. Emerging work on SGs indicates they may play important roles in cancer, neurodegenerative disease, and viral infection, often promoting survival. Yet much previous work on SGs formation and function has employed acute stress conditions, which may not accurately reflect the chronic stresses that manifest in human disease. We used prolonged nutrient starvation to investigate SG formation and function during chronic stress. Surprisingly, SGs that form under chronic nutrient starvation lack 40S ribosomes, do not actively exchange their constituent components with cytoplasmic pools, and promote cell death. These results imply that SG assembly and function in the context of prolonged nutrient starvation stress differ significantly from what has been described for acute stress conditions.\n\nSummary StatementThis work characterizes the mechanisms of formation of a novel type of stress granule that is induced in response to long-term starvation, and unlike previously described stress granules, functions in a pro-death capacity.

cell biology↗