Biology subjects

Ellis, S.

Publications and source records attributed to Ellis, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Proteolytic control of the SARS-CoV-2 furin cleavage site defines the phenotypic evolution from the pandemic to endemic state

The successive emergence of SARS-CoV-2 variants with altered tissue tropism has progressively decoupled transmissibility from lower respiratory tract pathogenicity. Omicron lineages transmit exceptionally well whilst limiting severe lung disease. Here, we demonstrate that this phenotype has evolved through two temporally distinct tissue-specific proteolytic controls at the Spike (S) furin cleavage site (FCS). At the virion level, cell-type-dependent furin-mediated FCS hyper-cleavage depletes S in lung but not nasal epithelial cells. At the infected cell membrane during cell-cell spread, TMPRSS2 mediates S FCS cleavage but is negatively regulated in the presence of ACE2. Tissue-specific solute carriers SLC6A19 and SLC6A20 sequester ACE2, thereby relieving inhibition of TMPRSS2 and enabling S FCS cleavage during cell-cell spread. Critically, whilst all SARS-CoV-2 lineages benefit from this latter pathway, Omicron variants have evolved exclusive dependence on it, a strategic consolidation that focuses S proteolytic activation to TMPRSS2 alone. The combined outcomes of S protein regulation across viral and cell membranes reveal how tissue-specific proteolytic optimisation drives Omicron's transmission fitness advantage in the upper respiratory tract but at the cost of heavy attenuation in the lower respiratory tract.

microbiology↗

bioRxiv2026

Quantitative Imaging and Characterization of Ganglioside Diversity in Mouse and Human Brain Tissues

Our understanding of how ganglioside species are spatially and quantitatively distributed within regions in mammalian remains limited. Studies are typically translated from rodents, assuming that gangliosides species contents within brain regions reflect the human condition. Herein, we provide a rich spatial ganglioside brain atlas describing the content, compositional differences, and concentrations of 48 ganglioside species across different regions in mouse and humans with no clinically known neurodegeneration. Our quantitative mass spectrometry imaging (MSI) approach allows non-rigid co-registration of mass spectrometry and microscopy images to allow precise spatial alignment and extraction of normalised ganglioside concentration data to reference mouse brain tissue anatomy and neuropathological annotated tissues for flexible downstream lipidomics analysis. Considerable differences and similarities are observed permitting region-specific ganglioside maps across twelve brain regions in wild type mouse. Gangliosides in mouse brain tissue generally preferred Cer 36:1;O2 configurations whereas human gangliosides in corresponding anatomically-annotated regions tended to favour Cer 38:1;O2 and longer backbones. Notably, this observation is more pronounced in gray matter compared to white matter. Collectively, this study defines the precise and quantitative ganglioside atlases across mice and human brains to guide and accelerate the discovery of biomarkers and therapeutic targets for brain diseases.

neuroscience↗

bioRxiv2026

Antiviral drug synergy and mutational signatures in different epithelial cell models of RSV and hPIV infection

Despite the huge global health burden presented by respiratory viruses, effective broad-spectrum antiviral therapeutic options remain limited. Here we evaluated the antiviral activity of four RNA-dependent RNA polymerase (RdRp) inhibitors, remdesivir, ribavirin, favipiravir, and molnupiravir, against respiratory syncytial virus (RSV) and human parainfluenza (hPIV) using monotherapy or dual-drug combinations with epithelial cell lines and primary human airway culture models. Remdesivir showed the greatest potency across both viruses, while ribavirin and favipiravir also demonstrated inhibition. Molnupiravir was active against RSVA but not hPIV3. Several dual-drug combinations, including remdesivir-favipiravir, remdesivir-molnupiravir and favipiravir-molnupiravir, produced marked synergy against RSVA, and more limited synergy for hPIV3. Antiviral efficacy was validated in primary airway epithelial cultures, where effective concentrations preserved epithelial integrity and attenuated viral disruption of ciliary function. Across both viruses, increasing antiviral exposure was associated with dose-dependent signature mutagenesis. Importantly, antivirals induced significantly higher RSVA mutation burden in the primary airway model. These findings highlight the therapeutic potential of RdRp inhibitor combinations for RSVA and hPIV3, provide mechanistic insight through antiviral-related mutational signatures and demonstrate advantages of the primary human airway culture model for development of effective multi-drug regimens and broad-spectrum antiviral preparedness. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/699296v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@1eb00dforg.highwire.dtl.DTLVardef@186358forg.highwire.dtl.DTLVardef@265181org.highwire.dtl.DTLVardef@1b10d0e_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2025

Quantification and Localisation of New Brain Lipid Synthesis Using Deuterium Oxide and High Resolution Mass Spectrometry

Myelin is the lipid-rich membrane that surrounds neuronal axons and is essential for neurological function in vertebrates. The development of therapeutics that stimulate myelin repair to treat demyelinating disorders such as multiple sclerosis is hampered by the inability to distinguish newly-synthesised from pre-existing myelin. This study aimed to develop a method to quantify and localise new myelin lipid synthesis in vivo. Deuterium oxide was administered for two weeks in the drinking water of mice fed normal chow, chow containing the demyelinating toxin cuprizone, or during spontaneous remyelination following cuprizone withdrawal. Liquid chromatography-tandem mass spectrometry and mass spectrometry imaging were used to quantify and localise the newly synthesised, deuterated lipids. While most glycerophospholipids were constitutively deuterated, deuteration of myelin-enriched sulfatides, hexosylceramides, and phosphatidylethanolamine plasmalogens was only apparent during remyelination. Deuterated hexosylceramide and phosphatidylethanolamine plasmalogen species were localised primarily to the corpus callosum, the white matter tract that is most heavily affected by cuprizone. Most deuterium atoms were found in the fatty acyl chains, indicative of de novo lipid synthesis. These methods provide the means to quantify and spatially profile dynamic lipid synthesis across diverse biological contexts, including understanding myelin homeostasis and preclinical evaluation of remyelinating therapeutics.

biochemistry↗

bioRxiv2025

Design and development of a SARS and MERS Combination Vaccine

This work was conducted during the COVID-19 pandemic prior to the licensing of any vaccines against COVID-19. Although several COVID-19 vaccines are now commercially available, this research on the development of a combination Severe Acute Respiratory Syndrome-associated Coronavirus (SARS-CoV), SARS-coronavirus 2 (SARS-CoV-2), and Middle Eastern Respiratory Syndrome (MERS) is still relevant and shows how a combination vaccine can be designed, produced and rapidly tested in the laboratory. We present the development of a combination vaccine designed to provide immunity against Severe Acute Respiratory Syndrome-associated Coronavirus (SARS-CoV), SARS-coronavirus 2 (SARS-CoV-2), and Middle Eastern Respiratory Syndrome (MERS). The primary objective of this vaccine design is twofold: to mitigate the burden of coronavirus and to address the specific vulnerability of regions prone to recurrent MERS outbreaks. Our combination vaccine incorporates antigenic components from zoonotic sources, specifically SARS-CoV, SARS-CoV-2, and MERS. We assess the impact of combining different Spike proteins S1 subunit antigens, due to its recognised immunogenic potential, and adjuvants on serum antibody titres, virus neutralizing capabilities, and inter-antigen immune responses. We report a robust and broad antibody response against SARS-CoV-2 and related coronaviruses, which was amplified by different adjuvant formulations, including alum, MPLA, CpG, and Squalene-in-Water Emulsion.

immunology↗

bioRxiv2025

Neutrophil myeloperoxidase as a functional biomarker for RSV severity: implications for in vitro therapeutic screening.

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infections in infants, yet effective therapeutics are lacking. The aim of this study is to develop an in vitro model that recapitulates key clinical outcomes in infants with RSV bronchiolitis to help accelerate the discovery of effective therapeutics. Neutrophil activation and influx into the airways are hallmarks of severe RSV infection, but these responses are difficult to quantify in clinical trials. Here we profile peripheral blood-derived neutrophils from infants with RSV admitted to the Paediatric Intensive Care Unit (PICU) and identify myeloperoxidase (MPO) as a key indicator of disease severity when compared to age matched controls. To mechanistically model this response, we established a paediatric airway epithelial air-liquid interface (ALI) system incorporating an endothelial layer and primary neutrophils to recapitulate the tissue microenvironment at the blood-airway barrier. Following RSV infection, neutrophil migration and activation were assessed using flow cytometry. The inclusion of an endothelial layer enhanced physiological relevance and more accurately replicated in vivo MPO responses. We then evaluated two antiviral candidates (remdesivir (RDV) and RSV604) to assess their ability to modulate neutrophil activation. While both compounds reduced viral load at 24 hours post-infection, only RSV604 attenuated MPO expression. These findings establish MPO as both a biomarker of RSV disease severity and a functional readout of therapeutic efficacy and demonstrate that targeting neutrophildriven inflammatory pathways may be critical for reducing pathology in infant RSV infection. Take home messageAntiviral drug discovery should include neutrophil MPO reduction as a readout of therapeutic efficacy. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=147 SRC="FIGDIR/small/682115v2_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@170058corg.highwire.dtl.DTLVardef@17c344corg.highwire.dtl.DTLVardef@14d79baorg.highwire.dtl.DTLVardef@172ac3c_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2025

Replication of SARS-CoV-2 Omicron lineages is defined by TMPRSS2 use in environments where ACE2 is complexed with solute carriers SLC6A19 and SLC6A20.

The Omicron variant of SARS-CoV-2 emerged in late 2021 and since then Omicron subvariants have continued to evolve and dominate globally. The viral S protein evolved towards highly efficient antibody evasion and replicative capacity in the upper respiratory tract resulting in high transmissibility. At the same time, the mutations acquired in the S protein diminish infection of the lung epithelium and pathogenic potential. The changing entry requirements for Omicron sub-lineages that lead to this shift in tropism remain poorly understood. We resolve the changing replication requirements of SARS-CoV-2 to be related to two distinct pools of ACE2. The first pool relates to ACE2s role in the renin angiotensin system (RAS) and this pool can complex with TMPRSS2 (RAS-ACE2). The second pool relates to ACE2s role as a protein solute carrier chaperone than cannot complex with TMPRSS2 (Chaperone ACE2). Here, we demonstrate that pre-Omicron lineages replicate in a TMPRSS2 dependent manner across both ACE2 pools, whilst Omicron lineages can only spread and replicate using chaperone ACE2. This provides a mechanistic basis for the evolving infectivity requirements of SARS-CoV-2 and furthermore provides approaches to track and monitor ACE2 utilizing coronaviruses. Graphical AbstractMechanistic basis for shift in SARS-CoV-2 tropism with the arrival of Omicron. A. Chaperone ACE2 is defined structurally as a heterodimer of dimers with a solute carrier protein-SLC6A19 or SLC6A20. Here this ACE2 structure can exist uncomplexed from TMPRSS2 and enables TMPRSS2 use by both pre-Omicron and Omicron lineages. B. Renin Angiotensin ACE2 is defined by ACE2 with an exposed collectrin-like domain (CLD), which enables binding of TMPRSS2 or ADAM-17. Here ACE2 can form a complex with TMPRSS2 in a manner that allows pre-Omicron but not Omicron lineages to utilize TMPRSS2 to facilitate infection. Here Omicron lineages are heavily attenuated as they cannot use TMPRSS2 to spread. C. to E. Based on single cell profiles, ACE2 can exist as a chaperone with SLC6A20 in C. the Nasal Cavity or D. primarily as RAS-ACE2 in the lung to respond to acute lung injury. E. The largest pool of ACE2 in our body resides within the small intestine on enterocytes and this further facilitates replication in this tissue by pre-Omicron and Omicron lineages. O_FIG O_LINKSMALLFIG WIDTH=198 HEIGHT=200 SRC="FIGDIR/small/663433v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@172aa47org.highwire.dtl.DTLVardef@109285eorg.highwire.dtl.DTLVardef@394f8corg.highwire.dtl.DTLVardef@958e31_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2025

Acute session of three endurance exercise intensities alters subcutaneous adipose tissue transcriptome in regular exercisers

The primary aim of this study was to compare the acute effects of three exercise intensities on abdominal subcutaneous adipose tissue (aSAT) transcriptome in regular exercisers. A total of 45 adults who exercise regularly were assigned to perform a single session of either low-intensity continuous (LOW; 60min at 30% VO2max; n=15), moderate-intensity continuous (MOD; 45min at 65% VO2max; n=15), or high-intensity interval exercise (HIGH; 10x1min at 90% VO2max interspersed with 1min active recovery; n=15). aSAT biopsy samples were collected before and 1.5hours after the exercise session for bulk RNA sequencing and targeted protein immunoassays. HIGH upregulated genes involved in cytokine secretion, insulin signaling, and proteolysis while MOD and LOW upregulated genes regulating ECM remodeling, ribosome biogenesis, and oxidative phosphorylation pathways. Exercise-induced changes in aSAT angiogenic, MAPK cascade, and clock genes, ERK protein phosphorylation, and circulating cytokines were similar after all three exercise treatments. Network analysis identified exercise-responsive gene clusters linked to cardiometabolic health traits. Cell-type analysis highlighted a heterogeneous response of aSAT cell types to exercise, with distinct patterns observed across exercise intensities. Collectively, our data characterizes early responses in aSAT after a single session of exercise. Because adaptations to exercise training stem from an accrual of responses after each session of exercise, these early responses to exercise are likely important contributors to the long-term structural and functional changes that occur in adipose tissue in response to exercise training.

physiology↗

bioRxiv2025

Predicting kinship dynamics during pre- and post reproductive life stages

Individuals relatedness to their groups often changes with age, potentially favouring age-linked trends in social behaviours, and these kinship dynamics have been invoked to explain the evolution of life history traits such as early reproductive cessation and post-reproductive helping. While models showed that simple demographic parameters (e.g., the rates of male and female philopatry vs dispersal, and of local vs non-local mating) suffice to predict the patterns of kinship dynamics breeders experience, they make the unrealistic assumptions that survival and fecundity are age-independent, thus fail to capture the full complexity of kinship dynamics. In particular, they cannot consistently predict how individuals relatedness to their groups should change during their pre- and post-reproductive phases. Here, we extend existing models of kinship dynamics to allow any age-linked changes in mortality and fecundity of both sexes. We describe the new model, and demonstrate its improved predictive power, by comparing the observed kinship dynamics of the killer whales to the predictions of the previously available models (assuming constant mortality and fecundity) and of our new model (considering any observed age-specific survival and fecundity). We show the new model better predicts the data, successfully capturing the observed three-stage female kinship dynamics: an individuals relatedness to her group decreases initially while juvenile, increases across reproductive lifespan, and decreases again during post-reproductive life. These predictions demonstrate the power of our model in generating new insights into the theory of social life history evolution (e.g., explaining why post-reproductive lifespan evolved yet are constrained).

evolutionary biology↗

bioRxiv2024

Discovery and Synthesis of GS-7682, a Novel Prodrug of a 4'-CN-4-Aza-7,9-Dideazaadenosine C-Nucleoside with Broad-Spectrum Potency Against Pneumo- and Picornaviruses and Efficacy in RSV-Infected African Green Monkeys.

Acute respiratory viral infections (ARVI), such as pneumovirus and respiratory picornavirus infections, exacerbate disease in COPD and asthma patients. A research program targeting respiratory syncytial virus (RSV) led to the discovery of GS-7682 (1) a novel phosphoramidate prodrug of a 4'-CN-4-aza-7,9-dideazaadenosine C-nucleoside GS-646089 (2) with broad antiviral activity against RSV EC50 = 3-46 nM, human metapneumovirus (hMPV) EC50 = 210 {+/-} 50 nM, human rhinovirus (RV) EC50 = 54-61 nM, and enterovirus (EV) EC50 = 83-90 nM. Prodrug optimization for cellular potency and lung cell metabolism identified the 5-methyl((S)-hydroxy(phenoxy)phosphoryl)-L-alaninate in combination with 2,3-diisobutyrate promoieties as optimal for high intracellular triphosphate formation in vitro and in vivo. 1 demonstrated significant reductions of viral loads in the lower respiratory tract of RSV-infected African green monkeys when administered once daily via intratracheal nebulized aerosol. Together these finding support additional evaluation of 1 and its analogs as a potential therapeutic for pneumo- and picornaviruses.

biochemistry↗

bioRxiv2024

Menopause has not evolved as a general trait in mammals: A response to "Do mammals have menopause?"

Reproductive senescence is widespread across mammals, but only a small number of species have physiological reproductive cessation and an extended post-reproductive lifespan. A recent commentary in Cell by Winkler & Goncalves (2023) suggests that menopause is actually a widespread trait of mammals, which would change our understanding of senescence and have implications for the study of menopause in humans. Here, we identify three main issues with the methodology of this commentary: the use of captive populations, the use of maximal lifespan, and misinterpretations of the data sources. We show that this methodology does not support the conclusions at the species-level, and conclude that, in line with the predictions of classic life-history theory, menopause is indeed a rare trait.

evolutionary biology↗

bioRxiv2024

High-resolution metabolite imaging: luteolinidin accumulates at the host-cyanobiont interface during cold-acclimation in Azolla symbioses

Aquatic ferns of the genus Azolla (Azolla) form highly productive symbioses with filamentous cyanobacteria fixing N2 in their leaf cavities, Nostoc azollae. Stressed symbioses characteristically turn red due to 3-deoxyanthocyanin (DA) accumulation, rare in angiosperms and of unknown function. To reveal DA functions upon cold acclimation and recovery, we integrated laser-desorption-ionization mass-spectrometry-imaging (LDI-MSI), a new A. filiculoides genome-assembly and annotation, and dual RNA-sequencing into phenotypic analyses of the symbioses. Azolla sp. Anzali recovered even when cold-induced DA-accumulation was inhibited by abscisic acid. Cyanobacterial filaments generally disappeared upon cold acclimation, and N. azollae transcript profiles were unlike those of resting stages formed in cold-resistant sporocarps, yet filaments re-appeared in leaf cavities of newly formed green fronds upon cold-recovery. The high transcript accumulation upon cold acclimation of AfDFR1 encoding a flavanone 4-reductase active in vitro suggested that the enzyme of the first step in the DA-pathway may regulate accumulation of DAs in different tissues. However, LDI-MSI highlighted the necessity to describe metabolite accumulation beyond class assignments as individual DA and caffeoylquinic acid metabolites accumulated differentially. For example, luteolinidin accumulated in epithelial cells, including those lining the leaf cavity, supporting a role for the former in the symbiotic interaction during cold acclimation. Summary statementDuring cold acclimation in Azolla symbioses, individual compounds from the same phenolic class accumulated in different host tissues: luteolinidin associated with biotic interactions at the symbiosis interface whilst apigenidin with photooxidative stress mitigation in the mesophyll.

plant biology↗

bioRxiv2023

Group size modulates kinship dynamics and selection on social traits

An individuals relatedness to its group may change with age due to demographic processes, and such kinship dynamics can shape age-linked social behaviors. Existing models, however, have focused almost exclusively on dispersal and mating, leaving the consequences of group size local variation unexplored. Here, we extend these models to incorporate such variation within a single, genetically connected meta-population. We then contrast predicted kinship dynamics and age-linked selection for helping/harming in coexisting smaller and larger groups in three typical social mammal systems characterized by distinct patterns of dispersal and mating, followed by exploring how group size local variation impacts female and male kinship dynamics across broader demographic contexts to clarify the population-genetic mechanisms. We show that, within the adult reproductive lifespans of these social systems, an individuals age-specific relatedness to others is higher, and changes faster (especially when younger), in smaller groups; consequently, smaller groups favor more extreme helping/harming (especially when younger) -- in social system with bi-sexual philopatry with non-local mating (e.g., whales) that favors female shifts from harming to helping with age (which explains the evolution of menopause and post-reproductive helping), such shifts are earlier in smaller groups. Further explorations suggest that, in a genetically connected population with group size local variation, group size effects on local relatedness are shaped by the relative strengths of ancestry dilution versus lineage coalescence, and kinship dynamics in a group reflect not only its local demographic conditions, but also those in coexisting groups of different size. Collectively, our study generates new insights into how female and male kinship dynamics emerge and vary under within-population group-size heterogeneity, and how such locally dynamic, varying kinship environments may help to explain variation in age-linked trends in social traits, such as the timing of menopause in social mammals.

evolutionary biology↗

bioRxiv2023

Socioecological drivers of injuries in female and male rhesus macaques (Macaca mulatta)

Competition over access to resources, such as food and mates, is believed to be one of the major costs associated with group living. Two socioecological factors suggested to predict the intensity of competition are group size and the relative abundance of sexually active individuals. However, empirical evidence linking these factors to injuries and survival costs is scarce. Here, we leveraged 10 years of data from free-ranging rhesus macaques where injuries inflicted by conspecifics are associated with a high mortality risk. We tested if group size and adult sex ratio predicted the occurrence of injuries and used data on physical aggression to contextualise these results. We found that males were less likely to be injured when living in larger groups, potentially due to advantages in intergroup encounters. Females, instead, had higher injury risk when living in larger groups but this was not explained by within-group aggression among females. Further, male-biased sex ratios predicted a weak increase in injury risk in females and were positively related to male-female aggression, indicating that male coercion during mating competition may be a cause of injuries in females. Overall, our results provide insights into sex differences in the fitness-related costs of competition and empirical evidence for long-standing predictions on the evolution of group living.

evolutionary biology↗

bioRxiv2023

Biomimetic robots reveal flexible adjustment of sexual signalling in a wild invertebrate.

Sexual signals are often structured in bouts, which can be adjusted in response to changes in the signallers physical and social environment. For example, we might expect individuals to adjust their own signalling behaviour in response to changes in the signalling behaviour of rivals, because this can affect their relative attractiveness to potential mates. In this study, we used a biomimetic robot to experimentally manipulate rival waving behaviour in a wild population of fiddler crabs (Afruca tangeri), and investigated whether this leads to changes in the activity and waving behaviour of a focal male. Analysing the focal males behaviour using hidden Markov models and linear hurdle models, we found no evidence that the focal males waving rate changed in response to changes in the behaviour of the robotic rival. However, bouts of waving lasted longer when the robotic rival was waving at a fast rate. Focal males were also less likely to enter their burrow when the robotic rival was waving, and spent less time in their burrow if they did enter. These results reveal tactical adjustment of behaviour by competing signallers, and highlight the flexible nature of bout-structured sexual displays.

animal behavior and cognition↗

bioRxiv2023

Bayesian inference of toothed whale lifespans

Accurate measures of lifespan and age-specific mortality are important both for understanding life history evolution and informing conservation and population management strategies. The most accurate data to estimate lifespan are from longitudinal studies, but for many species - especially those such as toothed whales that are wide-ranging and inhabit difficult-to-access environments - these longitudinal data are not available. However, other forms of age-structured data - such as from mass-strandings - are available for many toothed species, and using these data to infer patterns of age-specific mortality and lifespan remains an important outstanding challenge. Here we develop and test a Bayesian mortality model to derive parameters of a mortality function from age-structured data while accounting for potential error introduced by mistakes in age estimation, sampling biases and population growth. We then searched the literature to assemble a database of 269 published age-structured toothed whale datasets. We applied our mortality model to derive lifespan estimates for 32 species of female and 33 species of male toothed whale. We also use our model to characterise sex differences in lifespan in toothed whales. Our mortality model allows us to curate the most complete and accurate collection of toothed whale lifespans to date.

evolutionary biology↗

bioRxiv2023

The emergence of goblet inflammatory or ITGB6hi nasal progenitor cells determines age-associated SARS-CoV-2 pathogenesis

Children infected with SARS-CoV-2 rarely progress to respiratory failure, but the risk of mortality in infected people over 85 years of age remains high, despite vaccination and improving treatment options. Here, we take a comprehensive, multidisciplinary approach to investigate differences in the cellular landscape and function of paediatric (<11y), adult (30- 50y) and elderly (>70y) nasal epithelial cells experimentally infected with SARS-CoV-2. Our data reveal that nasal epithelial cell subtypes show different tropism to SARS-CoV-2, correlating with age, ACE2 and TMPRSS2 expression. Ciliated cells are a viral replication centre across all age groups, but a distinct goblet inflammatory subtype emerges in infected paediatric cultures, identifiable by high expression of interferon stimulated genes and truncated viral genomes. In contrast, infected elderly cultures show a proportional increase in ITGB6hi progenitors, which facilitate viral spread and are associated with dysfunctional epithelial repair pathways. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=155 SRC="FIGDIR/small/524211v2_ufig1.gif" ALT="Figure 1"> View larger version (61K): org.highwire.dtl.DTLVardef@dab12aorg.highwire.dtl.DTLVardef@1a57334org.highwire.dtl.DTLVardef@12e7983org.highwire.dtl.DTLVardef@2bbe6e_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2022

Outbreak of Highly Pathogenic Avian Influenza H5N1 in New England Seals

The recent incursion of Highly Pathogenic Avian Influenza A (H5N1) virus into North America and subsequent dissemination of virus across the continent, has had significant adverse impacts on domestic poultry, and has led to widespread mortality in many wild bird species. Here we report the recent spillover of H5N1 into marine mammals in the northeastern United States, with associated mortality on a regional scale. This spillover is coincident with a second wave of H5N1 in sympatric wild birds also experiencing regional mortality events. Viral sequences derived from both seal and avian hosts reveal distinct viral genetic differences between the two waves of infection. Spillover into seals was closely related to virus from the second wave, and one of eight seal-derived sequences had the mammalian adaptation PB2 E627K. One-Sentence SummaryAn outbreak of H5N1 in New England seals is the first known population-scale mammalian mortality event associated with the emerging highly pathogenic avian influenza clade 2.3.4.4b.

molecular biology↗