Biology subjects

Verdin, E.

Publications and source records attributed to Verdin, E..

At least 19 recordsLinked to original sources

bioRxiv2026

Curcumin and Sulforaphane Preserve Mobility in Aging Caenorhabditis elegans via Distinct yet Complementary Transcriptional Signatures

Aging involves a progressive decline in bodily functions, underscoring the need for interventions that enhance healthspan. In this study, we screened nine natural products in Caenorhabditis elegans using whole-organism phenotyping to assess mobility endpoints, and subsequently focused on curcumin, sulforaphane, and their combination. In replicated follow-up experiments, all three interventions improved late-adult mobility after Day 2 of adulthood. Sulforaphane and the combination provided the strongest gains, whereas curcumin showed a distinct benefit profile, with more pronounced effects on time active measures than on speed-based metrics. To examine associated molecular changes, we performed transcriptomic profiling on Day 3 adults. Curcumin was associated with lipid and sphingolipid remodeling together with reduced expression of several innate immune effectors, whereas sulforaphane induced glutathione-linked detoxification signatures involving multiple gst genes. The combination retained major features of both single-compound responses while adding combination-specific changes that broadened detoxification-associated signatures and extended repression of lectin-and lysozyme-associated genes. Transcription factor activity inference further supported SKN-1-linked detoxification responses under sulforaphane and the combination. Overall, these results suggest that curcumin and sulforaphane engage distinct yet partially convergent maintenance-related programs, and that their combination broadens the underlying molecular response without producing additive mobility gains. These findings motivate further testing of natural product combinations in healthspan-related contexts.

Systems Biology↗

bioRxiv2026

Confident Identification and Quantification of Mouse Brain Tissues Reveals Sirtuin 5-Dependent Regulation

Methylmalonylation is a non-enzymatic lysine post-translational modification derived from methylmalonyl-CoA, a reactive intermediate that accumulates during mitochondrial dysfunction and branched-chain amino acid catabolism. Although reported in models of methylmalonic acidemia, its broader distribution and functional relevance remain largely unexplored. Progress has been hindered by a key analytical challenge: methylmalonyl-and succinyl-lysine are isobaric (+100.0160 Da) and generate overlapping mass spectrometric fragmentation spectra, preventing confident identification in conventional proteomic workflows. Here, we establish a straightforward proteomic workflow that overcomes this barrier and enables confident identification and quantification of lysine methylmalonylation by combining antibody-based enrichment with data-independent acquisition mass spectrometry (DIA-MS). Anti-malonyl antibodies were used to enrich methylmalonylated peptides through cross-reactivity. Using synthetic peptide standards containing malonyl-, succinyl-, or methylmalonyl-lysine, we defined distinguishing analytical features including chromatographic retention time, ion mobility, and fragmentation patterns. Applying this approach to mouse brain tissues from Sirtuin-5 (SIRT5) knockout and wild-type mice, we identified 44 methylmalonylated peptides across 41 proteins, enriched in neuronal and myelin-associated proteins (NEFM, NEFL, MBP) and mitochondrial enzymes such as ADT1. Several sites were increased in SIRT5-deficient brains, consistent with regulation by this mitochondrial deacylase. Functional assays demonstrated that methylmalonylation of myelin basic protein (MBP) impairs lipid binding, linking this modification to myelin stability. Together, this workflow enables confident methylmalonylation identification and defines it as a widespread and regulated modification in the brain, providing a framework to study metabolically driven protein acylation in neurobiology and disease. SignificanceLysine methylmalonylation has remained largely unexplored due to its isobaric overlap with succinylation, which prevents confident identification using conventional proteomic workflows. Here, we establish an integrated strategy combining antibody-based enrichment, data-independent acquisition mass spectrometry, and orthogonal analytical features to resolve these modifications with high confidence. Applying this approach to mouse brain tissue reveals a SIRT5-regulated methylmalonylome enriched in mitochondrial and myelin-associated proteins, including myelin basic protein (MBP). Functional assays demonstrate that methylmalonylation impairs MBP lipid binding, linking this modification to myelin stability. Beyond this specific application, our workflow provides a generalizable framework to resolve isobaric post-translational modifications and expands the study of metabolically driven protein acylation in neurobiology and disease.

cell biology↗

bioRxiv2026

Ketone ester supplementation in aged mice reduces activation of B cell subsets

BackgroundAging in the immune system results in increased susceptibility to infections, exacerbated autoimmunity, and reduced responsiveness to vaccines. However, there are no current established interventions for immune aging. Ketogenic diets and fasting have been researched as interventions against other aspects of aging and age-related diseases, and they work in part by increasing circulating levels of ketone bodies, which have anti-inflammatory properties and can boost T cell function. Exogenous ketones, such as ketone esters, are currently being studied as a more accessible approach to obtain the benefits of ketone bodies through direct supplementation. Here, we investigated whether ketone ester supplementation improves immune function during aging. Aged (19-month-old) C57BL/6JN mice were given a diet supplemented with the ketone ester or a control diet for 15 weeks. ResultsWe found that the ketone ester diet decreased activation of B cells, especially age-associated B cells, in the spleen. The diet also reduced the proportion of age-associated B cells defined by CD11b and CD11c expression, though not of the broader CD21-CD23- population. Despite this decrease in activation, there was no impairment in antibody production, as mice on the ketone ester diet mounted a normal response to nitrophenyl-ovalbumin immunization. The ketone ester diet also reduced glucose dependence and translation in subsets of age-associated B cells. Treating splenocytes from aged mice with {beta}-hydroxybutyrate was sufficient to suppress B cell translation and reduced mTORC1 signaling, indicating that ketone bodies act directly on B cells. {beta}-hydroxybutyrate also decreased expression of T-bet, the signature transcription factor driving the autoimmune functions of age-associated B cells. ConclusionsOur study elucidates the effect of ketone esters on B cells in the context of aging and unveils a new immunoregulatory role of ketone bodies on B cells.

immunology↗

bioRxiv2026

BrainYears: A functional EEG-based brain age clock enables intervention-ready measurements of brain aging

Biological brain aging is a major determinant of cognitive decline and neurodegenerative disease, yet scalable and intervention-ready brain aging biomarkers remain limited. Here, we develop an electroencephalography (EEG)-based brain age clock using machine learning trained on high-dimensional neural features across the adult lifespan. Using 643 features captured from a Sens.ai headset and controller device, the model predicts chronological age with high accuracy (Pearson r = 0.92; MAE = 4.43 years) and yields an interpretable set of age-informative neural features capturing functional signatures of brain aging. Unlike MRI-based approaches, this EEG-based clock is non-invasive, transportable, cost- effective and suitable for repeated at-home longitudinal measurement. Furthermore, in a longitudinal neuromodulation program, BrainYears-predicted brain age decreased by a mean of -5.18 years in the intervention group whereas a minimal-exposure comparison group showed no change on average (+0.07 years). Together, this work introduces a functional brain aging biomarker and an intervention-ready platform for quantifying brain age modulation.

bioinformatics↗

bioRxiv2025

Multi-omics Analysis of Human Blood Cells Reveals Unique Features of Age-associated Type2 CD8 Memory T cells

Aging impacts immune function, but the mechanisms driving age-related changes in immune cell subsets remain unclear. To explore age-dependent changes in immune cell populations, we analyzed human peripheral blood mononuclear cells (PBMCs) from a cohort of healthy donors aged 20-82 years using a 36-color spectral flow cytometry panel focused on T cells. We identified a unique population of memory CD8 T cells, which lack CXCR3 and produce a Th2-like cytokine response, accumulate with age. We discovered an age-dependent bias in naive CD8 T cells toward Th2 cytokine production, accompanied by transcriptional and epigenetic changes supporting this phenotype. Moreover, health outcome association analysis linked the accumulation of these unique CXCR3- central memory CD8 T cells to asthma, chronic liver conditions, and type 2 diabetes. Together, our results support the model that an age-dependent drift in epigenetic regulation towards a Th2-like phenotype drives a pathogenic Th2-like immune population.

immunology↗

bioRxiv2025

Pathogenic tau inhibits synaptic plasticity by blocking eIF4B-mediated local protein synthesis

Activity-dependent modulation of synaptic strength is critical for encoding memories and it is inhibited in tauopathies including Alzheimers disease (AD) and Frontotemporal lobar degeneration with tau inclusions (FTLD-tau). Pathogenic tau accumulates in neurons where it obstructs synaptic plasticity. How tau blocks synaptic plasticity leading to memory loss is unclear. Here, we show that FTLD-tau inhibits plasticity by blocking activity-dependent protein synthesis in dendrites. In the plasticity-associated translatome, we identified a subset of downregulated translated mRNAs in FTLD-tau neurons that encode postsynaptic plasticity regulators. Protein synthesis was blocked by FTLD-tau binding to eIF4B which caused eIF4B dissociation from the translation initiation complex and reduced dendritic eIF4B levels. Inhibiting the tau-eIF4B interaction or enhancing eIF4B levels in FTLD-tau neurons restored local protein synthesis and synaptic plasticity. Together, this suggests that pathogenic tau binding to eIF4B disables the local synthesis of plasticity-related proteins that drive synapse strengthening and memory formation.

neuroscience↗

bioRxiv2025

Accumulation of SA-βGal High Cells in Human Naive T Cell Compartments Reveals a Stress-Adapted, Senescent-Like State

Aging is associated with a decline in immune function termed immunosenescence, characterized by accumulation of senescent-like immune cells and chronic inflammation, known as inflammaging. While senescence-associated {beta}-galactosidase (SA-{beta}Gal) activity is a well-established senescence marker, its functional significance and the precise cellular subsets affected within the T cell compartment remain unclear. Here, we identify and characterize a previously unrecognized subset of naive CD4 and CD8 T cells displaying high SA-{beta}Gal activity that significantly increases with age. Despite exhibiting hallmark features of senescence such as DNA damage, nuclear envelope disruption, loss of heterochromatin, and pronounced dysregulation of autophagy and lysosomal pathways, these SA-{beta}Gal-high naive T cells notably lack the canonical senescence marker p21CIP1 and retain robust proliferative capacity upon activation. Remarkably, naive CD4 SA-{beta}Gal-high T cells acquire cytotoxic properties including NK-like features, granzyme secretion, and the ability to induce paracrine DNA damage in endothelial cells. Mechanistically, we demonstrate that impaired autophagic flux contributes significantly to this phenotype. Our findings address critical knowledge gaps regarding the nature and functional plasticity of senescence-like states in naive T cells, highlighting a novel link between lysosomal-autophagic dysfunction, cellular stress adaptation, and inflammaging. Understanding this unique T cell population provides important insights into immune aging and offers potential targets to mitigate age-associated immune dysfunction and chronic inflammation.

immunology↗

bioRxiv2025

Multiplexed Targeted Spatial Mass Spectrometry Imaging Assays to monitor lipids and NAD+ metabolites in CD38 knockout mice exhibiting improved metabolism.

Mass spectrometry imaging (MSI) is a rapidly advancing technology that provides mapping of the spatial molecular landscape of tissues for a variety of analytes. Matrix-assisted laser desorption/ionization (MALDI)-MSI is commonly employed, however, confident in situ identification and accurate quantification of analytes remain challenging. We present a novel imaging methodology combining trapped ion mobility spectrometry (TIMS)-based parallel accumulation-serial fragmentation (PASEF) with MALDI ionization for targeted imaging parallel reaction monitoring (iprm-PASEF). We investigated the spatial distribution of lipids and metabolites in liver tissues from male wild-type and CD38 knockout mice (CD38-/-). CD38, an enzyme involved in nicotinamide adenine dinucleotide (NAD) metabolism, significantly influences liver metabolic function and contributes to age-related NAD decline. Although CD38 deletion previously was linked to improved metabolic phenotypes, the underlying spatial metabolic mechanisms are poorly understood. The spatial iprm-PASEF workflow enabled confident identification and differentiation of lipid isomers at the MS2 fragment ion level and confirmed increased NAD+ and decreased adenosine diphosphate ribose (ADPR), a by-product of NAD+ hydrolysis, in CD38-/- livers. This approach provided confident, specific, and robust MS2-based identification and quantification of fragment ions in spatial MSI experiments. Additionally, the innovative iprm-PASEF opens unprecedented opportunities for spatial metabolomics and lipidomics, offering spatially resolved insights into molecular mechanisms.

cell biology↗

bioRxiv2024

Utilizing blood single-cell transcriptomics to integrate intrinsic and systemic immune aging

Biomarkers of aging provide insight into the biological effects of interventions and diseases. However, most biomarkers today are based on measurements derived from bulk cell measurements, making it challenging to interpret whether an effect is due to changes in cell type composition (systemic factors) or a cell intrinsic effect. Single-cell RNA sequencing provides a unique platform to simultaneously compare aging-associated changes on both a cellular and bulk level. We first generated a single-cell combined automated human blood cell type and age predictor (clock) for six distinct human T cell subsets. We applied these tools to find acute COVID is associated with a shift in CD8+ cytotoxic cell proportions, while cell type proportions are stable in patients with HIV on long-term ART treatment (HIV+ART). Both COVID and HIV+ART were associated with an increase in naive CD8 T cell transcriptomic age. We further found our single-cell aging biomarker is linked to ribosomal gene expression and has a link to mean cellular transcript length. This study highlights the potential of single cell transcriptomic biomarkers for understanding how the human immune system is impacted by age-associated systemic changes in cell type composition and intrinsic cellular aging.

immunology↗

bioRxiv2024

Regulation of virion production by the ORF8 signal peptide across SARS-CoV-2 variants

The open reading frame 8 (ORF8), an accessory protein of SARS-CoV-2, is prone to deletions and mutations across different viral variants, which was first described in several Singapore variants. The reason why viral evolution favors loss or inactivation of ORF8 is not fully understood, although the effects of ORF8 on inflammation, immune evasion, and disease severity have been described. Here we show -using clinical ORF8-deficient viral isolates, virus-like particles (VLPs) and viral replicons- that ORF8 expression dampens viral particle production. ORF8 physically interacts with the viral Spike protein and induces Golgi fragmentation, overall contributing to less virus particle production. Using systematic ORF8 deletions, we mapped the particle-reducing function to its N-terminal signal peptide. Interestingly, this part of ORF8 is severely truncated in the recent XBB.1.5 variant, and when restored, suppresses viral particle production in the context of the entire viral genome. Collectively, our data supports the model that evolutionary pressure exists to delete ORF8 sequence and expression across SARS-CoV-2 variants to fully enable viral particle production. ImportanceSARS-CoV-2 variants continue to emerge worldwide with advantages in replication and immune evasion. Many variants have acquired distinct mutations in independent lineages to abolish ORF8 expression. To understand the molecular mechanisms behind this evolutionary trend, we utilized reverse genetics, molecular virology, and confocal microscopy to show that ORF8 has antiviral functions by dampening viral particle production and inducing Golgi stress during infection. Our data demonstrate that SARS-CoV-2 is continuing its adaptation to optimize viral particle production and other unknown aspects of viral infection.

microbiology↗

bioRxiv2023

Viral gene drive spread during herpes simplex virus 1 infection in mice

Gene drives are genetic modifications designed to propagate efficiently through a population. Most applications rely on homologous recombination during sexual reproduction in diploid organisms such as insects, but we recently developed a gene drive in herpesviruses that relies on co-infection of cells by wild-type and engineered viruses. Here, we developed a viral gene drive against human herpes simplex virus 1 (HSV-1) and showed that it propagated efficiently in vitro and during HSV-1 infection in mice. We observed high levels of co-infection and gene drive-mediated recombination in neuronal tissues during herpes encephalitis as the infection progressed from the site of inoculation to the peripheral and central nervous systems. In addition, we found evidence that a superinfecting gene drive virus could recombine with wild-type viruses during latent infection. These findings indicated that HSV-1 achieves high rates of co-infection and recombination during viral infection, a phenomenon that is currently underappreciated. Overall, this study showed that a viral gene drive could spread in vivo during HSV-1 infection, paving the way toward therapeutic applications.

microbiology↗

bioRxiv2023

A ketogenic diet reduces age-induced chronic neuroinflammation in mice

Beta-hydroxybutyrate (BHB) is a ketone body synthesized during fasting or strenuous exercise. Our previous study demonstrated that a cyclic ketogenic diet (KD), which induces BHB levels similar to fasting every other week, reduces midlife mortality and improves memory in aging mice. BHB actively regulates gene expression and inflammatory activation through non-energetic signaling pathways. Neither of these activities has been well-characterized in the brain and they may represent mechanisms by which BHB affects brain function during aging. First, we analyzed hepatic gene expression in an aging KD-treated mouse cohort using bulk RNA-seq. In addition to the downregulation of TOR pathway activity, cyclic KD reduces inflammatory gene expression in the liver. We observed via flow cytometry that KD also modulates age-related systemic T cell functions. Next, we investigated whether BHB affects brain cells transcriptionally in vitro. Gene expression analysis in primary human brain cells (microglia, astrocytes, neurons) using RNA-seq shows that BHB causes a mild level of inflammation in all three cell types. However, BHB inhibits the more pronounced LPS-induced inflammatory gene activation in microglia. Furthermore, we confirmed that BHB similarly reduces LPS-induced inflammation in primary mouse microglia and bone marrow-derived macrophages (BMDMs). BHB is recognized as an inhibitor of histone deacetylase (HDAC), an inhibitor of NLRP3 inflammasome, and an agonist of the GPCR Hcar2. Nevertheless, in microglia, BHBs anti-inflammatory effects are independent of these known mechanisms. Finally, we examined the brain gene expression of 12-month-old male mice fed with one-week and one-year cyclic KD. While a one-week KD increases inflammatory signaling, a one-year cyclic KD reduces neuroinflammation induced by aging. In summary, our findings demon-strate that BHB mitigates the microglial response to inflammatory stimuli, like LPS, possibly leading to decreased chronic inflammation in the brain after long-term KD treatment in aging mice.

immunology↗

bioRxiv2023

Chronically disrupted sleep induces senescence in the visceral adipose tissue of C57BL/6J mice

The role of sleep in systemic aging remains poorly understood, despite sleeps essential function in preserving overall health and the prevalence of reduced sleep quality in modern society. Although reduced sleep correlates with an elevated risk of age-related diseases in humans, the mechanisms underlying this are unclear. In this study, we established a link between sleep and aging by demonstrating that disrupting sleep in C57BL/6 mice drives cellular senescence in the visceral adipose tissue. Sleep disruption also led to increased oxidative stress and DNA damage, both recognized triggers for senescence induction. Cellular senescence is implicated in numerous age-related conditions which are associated with insufficient sleep, such as cardiovascular disease, type 2 diabetes, and chronic inflammation. Our findings identify an accumulation of senescent cells in the adipose tissue, which serves as a potential target through which disturbed sleep accelerates the aging process and elevates the risk of age-related diseases.

molecular biology↗

bioRxiv2023

β-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain

Loss of proteostasis is a hallmark of aging and Alzheimer disease (AD). Here, we identify {beta}-hydroxybutyrate ({beta}HB), a ketone body, as a regulator of protein solubility in the aging brain. {beta}HB is a small molecule metabolite which primarily provides an oxidative substrate for ATP during hypoglycemic conditions, and also regulates other cellular processes through covalent and noncovalent protein interactions. We demonstrate {beta}HB-induced protein insolubility across in vitro, ex vivo, and in vivo mouse systems. This activity is shared by select structurally similar metabolites, is not dependent on covalent protein modification, pH, or solute load, and is observable in mouse brain in vivo after delivery of a ketone ester. Furthermore, this phenotype is selective for pathological proteins such as amyloid-{beta}, and exogenous {beta}HB ameliorates pathology in nematode models of amyloid-{beta} aggregation toxicity. We have generated a comprehensive atlas of the {beta}HB-induced protein insolublome ex vivo and in vivo using mass spectrometry proteomics, and have identified common protein domains within {beta}HB target sequences. Finally, we show enrichment of neurodegeneration-related proteins among {beta}HB targets and the clearance of these targets from mouse brain, likely via {beta}HB-induced autophagy. Overall, these data indicate a new metabolically regulated mechanism of proteostasis relevant to aging and AD.

physiology↗

bioRxiv2023

CD38 regulates ovarian function and fecundity via NAD+ metabolism

Mammalian female reproductive lifespan is typically significantly shorter than life expectancy and is associated with a decrease in ovarian NAD+ levels. However, the mechanisms underlying this loss of ovarian NAD+ are unclear. Here, we show that CD38, a NAD+ consuming enzyme, is expressed in the ovarian extrafollicular space, primarily in immune cells, and its levels increase with reproductive age. Reproductively young mice lacking CD38 exhibit larger primordial follicle pools, elevated ovarian NAD+ levels, and increased fecundity relative to wild type controls. This larger ovarian reserve results from a prolonged window of follicle formation during early development. However, the beneficial effect of CD38 loss on reproductive function is not maintained at advanced age. Our results demonstrate a novel role of CD38 in regulating ovarian NAD+ metabolism and establishing the ovarian reserve, a critical process that dictates a females reproductive lifespan.

developmental biology↗

bioRxiv2023

Biological characterization of an emergent virus infecting vegetables in diversified production systems: physostegia chlorotic mottle virus

With the emergence of high throughput sequencing (HTS) technologies, the discovery of new plant viruses has outpaced their biological characterization. However, it is crucial to understand the biology of these viruses to evaluate the risks they pose for the production of crops and natural ecosystems and to manage them properly. In 2018, Physostegia chlorotic mottle virus (PhCMoV) was detected in Austria in a Physostegia plant (Lamiaceae) using HTS, and subsequent prepublication data sharing associated the presence of the virus with severe fruit symptoms on important crops like tomato, eggplant, and cucumber across nine European countries. This discovery led to a collaborative effort to understand better the viruss genetic diversity, host range, symptomatology, and distribution. Still, specific knowledge gaps remained. In this study, the authors address these gaps by examining the transmission mode, prevalence, and disease severity of PhCMoV. Bioassay and field survey confirmed the causal association between the presence of the virus and symptoms on tomato and eggplant. The investigation also mapped out the historical and geographic footprint of the virus, spanning back 30 years and including a new location, Switzerland. Based on field survey, PhCMoV was found to naturally infect 11 new host plant species across seven families, extending the host range of PhCMoV to 20 plant species across 14 plant families. Greenhouse assays with mechanical inoculation showed that yield losses could reach 100% depending on the phenological stage of the plant at the time of infection. The study also identified a polyphagous leafhopper species (Anaceratagallia sp.) as the natural vector of PhCMoV. PhCMoV was widespread in diversified vegetable farms in Belgium where tomato is grown in soil, occurring in approximately one-third of such farms. However, outbreaks were sporadic and it can be suggested that they were associated with specific cultural practices, such as the cultivation of perennial plants in tomato tunnels that can serve as a host for both the virus and its vector. To further explore this phenomenon and better manage the virus, studying the ecology of the Anaceratagalliae vector would be beneficial.

plant biology↗

bioRxiv2023

Development of a novel epigenetic clock resistant to changes in immune cell composition

Epigenetic clocks are age predictors that use machine-learning models trained on DNA CpG methylation values to predict chronological or biological age. Increases in predicted epigenetic age relative to chronological age (epigenetic age acceleration) are connected to aging-associated pathologies, and changes in epigenetic age are linked to canonical aging hallmarks. However, epigenetic clocks rely on training data from bulk tissues whose cellular composition changes with age. We found that human naive CD8+ T cells, which decrease during aging, exhibit an epigenetic age 15-20 years younger than effector memory CD8+ T cells from the same individual. Importantly, homogenous naive T cells isolated from individuals of different ages show a progressive increase in epigenetic age, indicating that current epigenetic clocks measure two independent variables, aging and immune cell composition. To isolate the age-associated cell intrinsic changes, we created a new clock, the IntrinClock, that did not change among 10 immune cell types tested. IntrinClock showed a robust predicted epigenetic age increase in a model of replicative senescence in vitro and age reversal during OSKM-mediated reprogramming.

genomics↗

bioRxiv2022

SARS-CoV-2 ORF8 limits expression levels of Spike antigen.

Survival from COVID-19 depends on the ability of the host to effectively neutralize virions and infected cells, a process largely driven by antibody-mediated immunity. However, with the newly emerging variants that evade Spike-targeting antibodies, re-infections and breakthrough infections are increasingly common. A full characterization of SARS-CoV-2 mechanisms counteracting antibody-mediated immunity is needed. Here, we report that ORF8 is a SARS-CoV-2 factor that controls cellular Spike antigen levels. ORF8 limits the availability of mature Spike by inhibiting host protein synthesis and retaining Spike at the endoplasmic reticulum, reducing cell-surface Spike levels and recognition by anti-SARS-CoV-2 antibodies. With limited Spike availability, ORF8 restricts Spike incorporation during viral assembly, reducing Spike levels in virions. Cell entry of these virions leaves fewer Spike molecules at the cell surface, limiting antibody recognition of infected cells. Our studies propose an ORF8-dependent SARS-CoV-2 strategy that allows immune evasion of infected cells for extended viral production.

microbiology↗