Biology subjects

Harvey, J.

Publications and source records attributed to Harvey, J..

16 recordsLinked to original sources

bioRxiv2026

Endothelial CD36 links arteriolar remodeling to metabolic and immune alterations in Alzheimer's disease

Alzheimer's disease (AD) is accompanied by profound cerebrovascular dysfunction, yet it remains unclear whether endothelial abnormalities reflect only vascular injury or altered regulatory states connecting vascular remodeling with metabolic and immune function. We integrated human brain transcriptomic and histopathological data with complementary mouse genetic and human iPSC-derived endothelial models to examine a CD36-centered endothelial-state framework in AD. Analysis of the Seattle Alzheimer's Disease Brain Cell Atlas identified three CD36-expressing endothelial populations; intermediate-CD36 Endo 2 predominated in both reference and AD samples, although the relative subset distributions differed. In hippocampal and cortical tissue from six AD patients, endothelial CD36 expression was observed in structurally abnormal arterioles with disrupted mural organization. In complementary mouse studies, endothelial PKD1 deficiency was accompanied by increased vascular CD36 and cerebrovascular abnormalities, whereas endothelial CD36 deletion altered lipid-metabolic and innate-immune-associated transcriptional programs, including AD-relevant genes and pathways, under metabolic-inflammatory stress. To assess whether distinct human endothelial backgrounds remained pharmacologically responsive, we treated control and CRISPR-engineered PSEN1 E276A iPSC-derived ECs with GS4898, a small molecule previously linked to arterial specification. Both maintained endothelial identity but displayed different baseline transcriptional profiles and shared as well as cell-line-dependent responses to GS4898. Together, our study identifies a CD36-associated vascular phenotype in human AD, demonstrates CD36-dependent regulation of brain endothelial metabolic-immune transcriptional programs in vivo, and reveals endothelial transcriptional responsiveness to pharmacologic perturbation. The observed endothelial transcriptional plasticity may provide a basis for developing state-selective therapeutic strategies targeting cerebrovascular dysfunction in AD.

neuroscience↗

bioRxiv2026

Dectin-2-dependent adaptive immunity governs intestinal clearance of systemic Candida albicans

Effective immunity to Candida albicans requires coordination between innate recognition and induction of adaptive CD4 T cell responses. While the C-type lectin receptor Clec4n (Dectin-2) is known to drive Th17 polarization, its role in shaping tissue-specific adaptive responses remains incompletely understood. Here, we used an OT-II antigen-specific CD4 T cell transfer model combined with OVA-expressing Candida albicans to dissect the function of Dectin-2 during systemic infection. We found that Dectin-2 is dispensable for antigen presentation and CD4 T cell priming in gut-draining lymph nodes. Moreover, we show that Dectin-2-deficient mice fail to control fungal growth in the intestinal mucosa, despite elevated local production of IL-17A and GM-CSF. The increased susceptibility of the Dectin-2-deficient mice was associated with impaired neutrophil activation in the intestinal mucosa. These findings identify a tissue-specific checkpoint role for Dectin-2, linking balanced adaptive Th17 cytokine responses to granulocyte function, and revealing a previously unappreciated mechanism required for anti-fungal immune regulation at intestinal mucosal surface.

immunology↗

bioRxiv2025

Clec7a-mediated regulation of Killer-like Lectin Receptor expression controls T cell immunity

Clec7a is a C-type lectin receptor (CLR) originally defined for its non-redundant role in anti-fungal immunity. Subsequent work has broadened this view, implicating Clec7a in host defense against diverse pathogens and in the pathogenesis of cancer, autoimmunity, neuroinflammation, and developmental disorders. How a single innate receptor orchestrates such wide-ranging outcomes remains unresolved. We previously demonstrated that dendritic cell (DC)-expressed Clec7a is required for protective anti-fungal immunity in the gastrointestinal tract through regulation of fungus-specific CD4 T cell responses. Here, we show that Clec7a controls the expression of multiple C-type lectins in DCs, including a cluster of killer lectin-like receptors (KLRs). Notably, we reveal that these KLRs directly regulate DC function and control CD4 T cell responses. These findings define a novel Clec7a-KLR axis that integrates innate and adaptive immunity, highlighting a regulatory pathway with broad relevance for immune homeostasis, inflammation, and host defense.

immunology↗

bioRxiv2025

KLRE1 shapes antifungal immunity by tuning dendritic cell and T cell activation through distinct heterodimeric partners

Dendritic cells (DCs) instruct adaptive immunity by integrating inflammatory cues to regulate co-signalling molecules and T cell activation. We recently discovered that the pattern recognition receptor Dectin-1 (Clec7a) controls expression of a network of killer lectin-like receptors (KLRs), including KLRI1 and KLRI2, which regulate adaptive immune responses. Here, we identify KLRE1 as a key regulator of DC phenotype and function, acting through distinct heterodimeric interactions with KLRI1 and KLRI2. KLRE1 is expressed by tissue-resident and bone marrow-derived DCs and is dynamically regulated by inflammatory signals, including fungal stimuli. Mechanistically, KLRE1:KLRI1 heterodimers promote DC activation, increasing CD40, CD80, CD86, and MHC-II, whereas KLRE1:KLRI2 heterodimers restrain activation. Differential regulation of KLRI1 and KLRI2 by inflammatory signals shapes heterodimer availability and immune outcomes under distinct conditions. Functionally, KLRE1 deficiency enhances DC activation and T cell responses in vitro and in vivo during Candida albicans infection. Strikingly, KLRI1- and KLRI2-deficient mice showed opposite survival outcomes during systemic candidiasis, despite similar fungal burdens, implicating KLRE1 heterodimers in disease tolerance rather than pathogen clearance. Protection in KLRI1-deficient mice was associated with a more balanced T cell response, whereas susceptibility to infection associated with KLRI2 deficiency resulted from increased T cell activation and migratory potential, leading to systemic inflammation and renal dysfunction. Thus, KLRE1 heterodimers fine-tune DC-driven T cell immunity, balancing protection and immunopathology during fungal infection.

immunology↗

bioRxiv2025

Systemic infections alter cortical transcriptional signatures in Alzheimer's disease

Alzheimers disease (AD) is characterized by neuroinflammation, yet the impact of concurrent systemic infections on the AD brain remains poorly understood. We investigated the molecular mechanisms underlying the central nervous system response to systemic infections in AD by analyzing RNA sequencing data generated in the prefrontal cortex from 202 post-mortem donors (113 AD, 89 controls), where we stratified by the presence of a respiratory infection at the time of death. We identified 763 significantly differentially expressed genes (DEGs) between AD and controls without infection, which were enriched for oxidative phosphorylation and neurodegenerative pathways. In contrast, 122 DEGs distinguished AD from controls during infection, with 57 genes uniquely altered in AD in the presence of infection, including MAPK4, VAV3, and POU3F4, implicating infection-dependent mechanisms of vascular and immune regulation. Pathway activity analysis revealed that infection in AD suppresses some immune and vascular pathways, while enhancing transcriptional and developmental programs. Weighted gene co-expression network analysis uncovered three key modules: one module strongly associated with AD, enriched for aging and signal transduction; one module linked to both AD and infection, highlighting cytoskeletal remodelling and host-pathogen interactions; and one module specific to infection, enriched in astrocytes, pericytes, and endothelial cells, implicating blood-brain barrier dysfunction. These findings suggest that systemic respiratory infections reshape transcriptional programs in the AD brain, dampening immune effector pathways and engaging vascular and host-pathogen processes in blood-brain-barrier-associated cell types. Our results highlight the complex interplay between systemic infection, neuroinflammation, and vascular responses in AD.

neuroscience↗

bioRxiv2025

A Cell Type Enrichment Analysis Tool for Brain DNA Methylation Data (CEAM)

DNA methylation signatures are highly cell type-specific, yet most epigenome-wide association studies (EWAS) are performed on bulk tissue, potentially obscuring critical cell type-specific patterns. Existing computational tools for detecting cell type-specific DNAm changes are often limited by the accuracy of cell type deconvolution algorithms. Here, we introduce CEAM (Cell-type Enrichment Analysis for Methylation), a robust and interpretable framework for cell type enrichment analysis in DNA methylation data. CEAM applies over-representation analysis with cell type-specific CpG panels from Illumina EPIC arrays derived from nuclei-sorted cortical post-mortem brains from neurologically healthy aged individuals. The constructed CpG panels were systematically evaluated using both simulated datasets and published EWAS results from Alzheimers disease, Lewy body disease, and multiple sclerosis. CEAM demonstrated resilience to shifts in cell type composition, a common confounder in EWAS, and remained accurate across a wide range of differentially methylated positions, underscoring its flexibility. Application to existing EWAS findings generated in neurodegenerative diseases revealed enrichment patterns concordant with established disease biology, confirming CEAMs biological relevance. The workflow is publicly available as an interactive Shiny app (https://um-dementia-systems-biology.shinyapps.io/CEAM/) enabling rapid, interpretable analysis of cell type-specific DNAm changes from bulk EWAS.

genomics↗

bioRxiv2025

The macroecology of immunity: predominant influence of climate on invertebrate immune response

The immune system is the primary defense against parasites. With the ever-increasing rate of disease, epidemiologic models considering geographic variation in immune responses could prove useful. Despite increasing interest in the macroecology of parasitism and infectious diseases, we know little about the macroecology of immune responses. Host characteristics, parasite exposure, and environmental factors can all affect immunity, but how these factors interact to shape spatial variation in the strength of immune responses remains unexplored. We captured odonates (dragonflies and damselflies) and their conspicuous ectoparasitic mites across a geographic area spanning the temperate and boreal forest biomes in eastern Canada. We then conducted immune response bioassays on 1,237 individuals from 63 odonate species. We used linear regressions and structural equation models to relate immune responses to host body size, parasite load, pH, temperature, and precipitation while accounting for evolutionary relationships among host species. We found significant differences in the strength of immune response among host individuals, and this variation was best explained by climatic conditions, specifically decreasing with precipitation and, to a lesser degree, temperature. While host species significantly differed in immune response strength, we found no effect of host body size, evolutionary relationships among hosts, or parasitism on immune response. Our study investigating the drivers of immune response across dozens of species spread across two biomes is the most comprehensive to date. Climatic conditions have a strong influence on host immune response, regardless of host characteristics or parasitism rates. In this specific case, strong immune responses were associated with low levels of annual precipitation, which could relate to the role of cuticular melanin content in desiccation resistance, and the melanin-based encapsulation response being a byproduct of this adaptation. A spatially-explicit understanding of the biological processes affecting immunity could improve epidemiological models of disease risk that inform disease management globally.

immunology↗

bioRxiv2025

Epigenomic subtypes of late-onset Alzheimer's disease reveal distinct microglial signatures

Growing evidence suggests that clinical, pathological, and genetic heterogeneity in late-onset Alzheimers disease contributes to variable therapeutic outcomes, potentially explaining many trial failures. Advances in molecular subtyping through proteomic and transcriptomic profiling reveal distinct patient subgroups, highlighting disease complexity beyond amyloid-beta plaques and tau tangles. This insight underscores the need to expand molecular subtyping across new molecular layers, to identify novel drug targets for different patient subgroups. In this study, we analyzed genome-wide DNA methylation data from three independent postmortem brain cohorts (n = 831) to identify epigenetic subtypes of late-onset Alzheimers disease. Unsupervised clustering approaches were employed to identify distinct DNA methylation patterns, with subsequent cross-cohort validation to ensure robustness and reproducibility. To explore the cell-type specificity of the identified epigenomic subtypes, we characterized their methylation signatures utilizing DNA methylation profiles derived from purified brain cells. Transcriptomic data from bulk and single-cell RNA sequencing were integrated to examine the functional impact of epigenetic subtypes on gene expression profiles. Finally, we performed statistical analyses to investigate associations between these DNA methylation-defined subtypes and clinical or neuropathological features, aiming to elucidate their biological significance and clinical implications. We identified two distinct epigenomic subtypes of late-onset Alzheimers disease, each defined by reproducible DNA methylation patterns across three cohorts. Both subtypes exhibit cell-type-specific DNA methylation profiles. Subtype 1 and subtype 2 show significant microglial methylation enrichment, with odds ratios (OR) of 1.6 and 1.3, respectively. The minimal overlap between them suggests distinct microglial states. Additionally, subtype 2 displays strong neuronal (OR = 1.6) and oligodendrocyte (OR = 3.6) enrichment. Bulk transcriptomic analyses further highlighted divergent biological mechanisms underpinning these subtypes, with subtype 1 enriched for immune-related processes, and subtype 2 characterized predominantly by neuronal and synaptic functional pathways. Single-cell transcriptional profiling of microglia revealed subtype-specific inflammatory states: subtype 1 represented a state of chronic innate immune hyperactivation with impaired resolution, while subtype 2 exhibited a more dynamic inflammatory profile balancing pro-inflammatory signaling with reparative and regulatory mechanisms. This study highlights the molecular heterogeneity of late-onset Alzheimers disease by identifying two epigenetic subtypes with distinct cell-type-specific DNA methylation patterns. Their alignment with previously defined molecular classifications underscores their relevance in disease pathogenesis. By linking these subtypes to inflammatory microglial activity, our findings provide a foundation for future precision medicine approaches in Alzheimers research and treatment.

genomics↗

bioRxiv2024

Impact of variants and vaccination on nasal immunity across three waves of SARS-CoV-2

SARS-CoV-2 infection and COVID-19 disease vary with respect to viral variant and host vaccination status. However, how vaccines, emergent variants, and their intersection shift host responses in the human nasal mucosa remains uncharacterized. We and others have shown during the first SARS-CoV-2 wave that a muted nasal epithelial interferon response at the site of infection underlies severe COVID-19. We sought to further understand how upper airway cell subsets and states associate with COVID-19 phenotypes across viral variants and vaccination. Here, we integrated new single-cell RNA-sequencing (scRNA-seq) data from nasopharyngeal swabs collected from 67 adult participants during the Delta and Omicron waves with data from 45 participants collected during the original (Ancestral) wave in our prior study. By characterizing detailed cellular states during infection, we identified changes in epithelial and immune cells that are both unique and shared across variants and vaccination status. By defining SARS-CoV-2 RNA+ cells for each variant, we found that Delta samples had a marked increase in the abundance of viral RNA+ cells. Despite this dramatic increase in viral RNA+ cells in Delta cases, the nasal cellular compositions of Delta and Omicron exhibit greater similarity, driven partly by myeloid subsets, than the Ancestral landscapes associated with specialized epithelial subsets. We found that vaccination prior to infection was surprisingly associated with nasal macrophage recruitment and activation rather than adaptive immune cell signatures. While patients with severe disease caused by Ancestral or Delta variants had muted interferon responses, Omicron-infected patients had equivalent interferon responses regardless of disease severity. Our study defines the evolution of cellular targets and signatures of disease severity in the upper respiratory tract across SARS-CoV-2 variants, and suggests that intramuscular vaccines shape myeloid responses in the nasal mucosa upon SARS-CoV-2 infection.

immunology↗

bioRxiv2023

Epigenetic insights into neuropsychiatric and cognitive symptoms in Parkinson's disease: A DNA co-methylation network analysis

Parkinsons disease is a highly heterogeneous disorder, encompassing a complex spectrum of clinical presentation including motor, sleep, cognitive and neuropsychiatric symptoms. We aimed to investigate genome-wide DNA methylation networks in post-mortem Parkinsons disease brain samples and test for region-specific association with common neuropsychiatric and cognitive symptoms. Of traits tested, we identify a co-methylation module in the substantia nigra with significant correlation to depressive symptoms and with ontological enrichment for terms relevant to neuronal and synaptic processes. Notably, expression of the genes annotated to the methylation loci present within this module are found to be significantly enriched in neuronal subtypes within the substantia nigra. These findings highlight the potential involvement of neuronal-specific changes within the substantia nigra with regard to depressive symptoms in Parkinsons disease.

neuroscience↗

bioRxiv2020

Detection of clustered anomalies in single-voxel morphometry as a rapid automated method for identifying intracranial aneurysms.

Unruptured intracranial aneurysms (UIAs) are prevalent neurovascular anomalies which, in rare circumstances, rupture to create a catastrophic subarachnoid haemorrhage. Although surgical management can reduce rupture risk, the majority of IAs exist undiscovered until rupture. Current computer-aided UIA diagnoses sensitively detect and measure UIAs within cranial angiograms, but remain limited to low specificities whose output requires considerable neuroradiologist interpretation not amenable to broad screening efforts. To address these limitations, we propose an analysis which interprets single-voxel morphometry of segmented neurovasculature to identify UIAs. Once neurovascular anatomy of a specified resolution is segmented, interrelationships between voxel-specific morphometries are estimated and spatially-clustered outliers are identified as UIA candidates. Our automated solution detects UIAs within magnetic resonance angiograms (MRA) at unmatched 86% specificity and 81% sensitivity using 3 minutes on a conventional laptop. Our approach does not rely on interpatient comparisons or training datasets which could be difficult to amass and process for rare incidentally discovered UIAs within large MRA files, and in doing so, is versatile to user-defined segmentation quality, to detection sensitivity, and across a range of imaging resolutions and modalities. We propose this method as a unique tool to aid UIA screening, characterisation of abnormal vasculature in at-risk patients, morphometry-based rupture risk prediction, and identification of other vascular abnormalities. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/216812v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@166f3aborg.highwire.dtl.DTLVardef@76ea1org.highwire.dtl.DTLVardef@1f03619org.highwire.dtl.DTLVardef@16fd797_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract C_FIG Highlights O_LIRapid and automated detection of unruptured intracranial aneurysms (UIAs) in MRAs C_LIO_LIHighly specific, sensitive UIA detection to reduce radiologist input for screening C_LIO_LIDetection is versatile to image resolution, modality and has tuneable mm sensitivity C_LI

bioinformatics↗

bioRxiv2020

Pan-cancer Drivers are Recurrent Transcriptional Regulatory Heterogeneities in Early-stage Luminal Breast Cancer

The heterogeneous composition of solid tumors is known to impact disease progression and response to therapy. Malignant cells coexist in different regulatory states that can be accessed transcriptomically by single-cell RNA sequencing, but these methods have many caveats related to sensitivity, noise, and sample handling. We revised a statistical fluctuation analysis called stochastic profiling to combine with 10-cell RNA sequencing, which was designed for laser-capture microdissection (LCM) and extended here for immuno-LCM. When applied to a cohort of late-onset, early-stage luminal breast cancers, the integrated approach identified thousands of candidate regulatory heterogeneities. Intersecting the candidates from different tumors yielded a relatively stable set of 710 recurrent heterogeneously expressed genes (RHEGs) that were significantly variable in >50% of patients. RHEGs were not strongly confounded by dissociation artifacts, cell cycle oscillations, or driving mutations for breast cancer. Rather, we detected RHEG enrichments for epithelial-to-mesenchymal transition genes and, unexpectedly, the latest pan-cancer assembly of driver genes across cancer types other than breast. Heterogeneous transcriptional regulation conceivably provides a faster, reversible mechanism for malignant cells to evaluate the effects of potential oncogenes or tumor suppressors on cancer hallmarks. Statement of significanceProfiling intratumor heterogeneity of luminal breast carcinoma cells identifies a recurrent set of genes suggesting sporadic activation of pathways known to drive other types of cancer.

cancer biology↗

bioRxiv2019

Imbalance in the response of pre- and post-synaptic components to amyloidopathy

Alzheimers disease (AD)-associated synaptic dysfunction drives the progression of pathology from its earliest stages. A{beta} species, both soluble and in plaque deposits, have been causally related to the progressive, structural and functional impairments observed in AD. It is, however, still unclear how A{beta} plaques develop over time and how they progressively affect local synapse density and turnover. Here we observed, in a mouse model of AD, that A{beta} plaques grow faster in the earlier stages of the disease and if their initial area is > 500 {micro}m2; this may be due to deposition occurring in the diffuse part of the plaque. In addition, synaptic turnover is higher in the presence of amyloid pathology and this is paralleled by a reduction in pre-but not post-synaptic densities. Plaque proximity does not appear to have an impact on synaptic dynamics. These observations indicate an imbalance in the response of the pre- and post-synaptic terminals and that therapeutics, alongside targeting the underlying pathology, need to address changes in synapse dynamics.

neuroscience↗

bioRxiv2019

Transcriptional signatures of progressive neuropathology in transgenic tau and amyloid mouse models.

The onset and progression of Alzheimers disease (AD) is characterized by increasing intracellular aggregation of hyperphosphorylated tau protein and accumulation of {beta}-amyloid (A{beta}) in the neocortex. Despite recent success in identifying genetic risk factors for AD the transcriptional mechanisms involved in disease progression are not fully understood. We used transgenic mice harbouring human tau (rTg4510) and amyloid precursor protein (J20) mutations to investigate transcriptional changes associated with the development of both tau and amyloid pathology. Using highly-parallel RNA sequencing we profiled transcriptional variation in the entorhinal cortex at four time points identifying robust genotype-associated differences in entorhinal cortex gene expression in both models. We quantified neuropathological burden across multiple brain regions in the same individual mice, identifying widespread changes in gene expression paralleling the development of tau pathology in rTg4510 mice. Differentially expressed transcripts included genes associated with familial AD from genetic studies of human patients, and genes annotated to both common and rare variants identified in GWAS and exome-sequencing studies of late-onset sporadic AD. Systems-level analyses identified discrete co-expression networks associated with the progressive accumulation of tau, with these enriched for genes and pathways previously implicated in the neuro-immunological and neurodegenerative processes driving AD pathology. Finally, we report considerable overlap between tau-associated networks and AD-associated co-expression modules identified in the human cortex. Our data provide further support for an immune-response component in the accumulation of tau, and reveal novel molecular pathways associated with the progression of AD neuropathology.

genomics↗

bioRxiv2018

Sexual Dichromatism Drives Diversification Within a Major Radiation of African Amphibians

Theory predicts that sexually dimorphic traits under strong sexual selection, particularly those involved with intersexual signaling, can accelerate speciation and produce bursts of diversification. Sexual dichromatism (sexual dimorphism in color) is widely used as a proxy for sexual selection and is associated with rapid diversification in several animal groups, yet studies using phylogenetic comparative methods to explicitly test for an association between sexual dichromatism and diversification have produced conflicting results. Sexual dichromatism is rare in frogs, but it is both striking and prevalent in African reed frogs, a major component of the diverse frog radiation termed Afrobatrachia. In contrast to most other vertebrates, reed frogs display female-biased dichromatism in which females undergo color transformation, often resulting in more ornate coloration in females than in males. We produce a robust phylogeny of Afrobrachia to investigate the evolutionary origins of sexual dichromatism in this radiation and examine whether the presence of dichromatism is associated with increased rates of net diversification. We find that sexual dichromatism evolved once within hyperoliids and was followed by numerous independent reversals to monochromatism. We detect significant diversification rate heterogeneity in Afrobatrachia and find that sexually dichromatic lineages have double the average net diversification rate of monochromatic lineages. By conducting trait simulations on our empirical phylogeny, we demonstrate our inference of trait-dependent diversification is robust. Although sexual dichromatism in hyperoliid frogs is linked to their rapid diversification and supports macroevolutionary predictions of speciation by sexual selection, the function of dichromatism in reed frogs remains unclear. We propose that reed frogs are a compelling system for studying the roles of natural and sexual selection on the evolution of sexual dichromatism across both micro- and macroevolutionary timescales.

evolutionary biology↗

bioRxiv2018

Evolutionary insights into Bean common mosaic necrosis virus and Cowpea aphid borne mosaic virus using global isolates and thirteen new near complete genomes from Kenya

Plant viral diseases are one of the major limitations in legume production within sub Saharan Africa (SSA), as they account for up to 100 % in production losses within smallholder farms. In this study, field surveys were conducted in the western highlands of Kenya with viral symptomatic leaf samples collected. Subsequently, next-generation sequencing was carried out. The main aim was to gain insights into the selection pressure and evolutionary relationships of Bean common mosaic necrosis virus (BCMNV) and Cowpea aphid-borne mosaic virus (CABMV), within symptomatic common beans and cowpeas. Eleven near complete genomes of BCMNV and two for CABMV sequences were obtained from SSA. Bayesian phylogenomic analysis and tests for differential selection pressure within sites and across tree branches of the viral genomes was carried out. Three distinct well-supported clades were identified across the whole genome tree, and were in agreement with individual gene trees. Selection pressure analysis within sites and across phylogenetic branches suggested both viruses were evolving independently, but under strong purifying selection, with a slow evolutionary rate. These findings provide valuable insights on the evolution of BCMNV and CABMV genomes and their relationship to other viral genomes globally. These results will contribute greatly to the knowledge gap surrounding the phylogenomic relationship of these viruses, particularly for CABMV, for which there are few genome sequences available, and support the current breeding efforts towards resistance for BCMNV and CABMV.

evolutionary biology↗