Biology subjects

Chang, Y.-C.

Publications and source records attributed to Chang, Y.-C..

At least 19 recordsLinked to original sources

bioRxiv2026

A Sterol-Binding Cavity Underlies Sterol Recognition and Differential Activation of the ABCG5/G8

Sterol homeostasis depends on the coordinated regulation of endogenous cholesterol synthesis, dietary sterol absorption, and sterol excretion. The heterodimeric ATP-binding cassette sterol transporter ABCG5/G8 plays an important role in eliminating excess sterols by participating in reverse cholesterol transport and transintestinal cholesterol efflux. The molecular mechanism of sterol recognition and transport by ABCG5/G8 remains poorly understood. Here, we determined the cryo-electron microscopy (cryo-EM) structure of human ABCG5/G8 in complex with ergosterol. The structure revealed a sterol-binding site at the transmembrane domain (TMD) interface between the subunits ABCG5 and ABCG8, adjacent to the conserved aromatic clamp motif. Tyrosine 432 (Y432) on ABCG5, a key residue within the aromatic clamp, lies near the tetracyclic ring of ergosterol. Additionally, to assess the effect of different sterols on transporter activity, we performed molecular dynamic simulations and in vitro ATPase assays in the presence of cholesterol, cholesteryl hemisuccinate (CHS), and ergosterol. Ergosterol exhibited more favorable interactions with ABCG5/G8 and stimulated ATPase activity more effectively than either cholesterol or CHS, representing the first biochemical characterization of ABCG5/G8 activity in response to a non-cholesterol sterol. Furthermore, substitution of Y432 with the canonical phenylalanine in ABCG family abolished the differential ATPase response to ergosterol, with the mutant displaying similar activity levels in the presence of ergosterol and cholesterol. Together, our structural and biochemical findings reveal a conserved sterol-binding site within ABCG5/G8 and demonstrate direct evidence that distinct sterols differentially modulate ABCG sterol transporter activity and that the degenerative aromatic clamp motif in ABCG5 contributes to sterol-dependent functional selectivity.

biochemistry↗

bioRxiv2026

Prospective pan-cancer phosphoproteomics at clinical scale extends therapeutic options in precision oncology

Genomics-guided precision oncology has improved survival in cancer entities with actionable mutations but cannot capture oncogenic signaling that manifests at the protein level. Here, we report a prospective, real-world pan-cancer study profiling proteomes and phosphoproteomes of 1,998 tumor samples from adults and children with rare or advanced cancers enrolled in the German precision oncology programs DKFZ/NCT/DKTK MASTER, CATCH and INFORM and their molecular tumor boards (MTBs). We developed tumor proteome activity status (TOPAS) scores for 46 clinically relevant kinases, an immune activity score capturing antigen presentation and T-cell activation and identified therapeutically targetable cell-surface proteins for 94% of patients. These readouts enhance MTB recommendations by exposing actionable non-genomic kinase activity, refining interpretation of oncogenic genome alterations, and highlighting cell-surface treatment options. Three proof-of-concept analyses indicate clinical utility including kinase activity-stratified pazopanib response in sarcoma, immune activity score-tracked checkpoint-inhibitor outcomes pan-cancer, and a phosphoproteomic biomarker distinguishing EGFR-inhibitor response in chordoma.

cancer biology↗

bioRxiv2026

Direct probabilistic quantification of mosaic loss of chromosome Y from sequencing data

Loss of chromosome Y (LOY) is the most common aneuploidy in aging men and is increasingly recognized as a marker of aging and genomic instability. Because LOY occurs in mosaic form, its degree reflects the fraction of cells lacking the Y chromosome. Existing SNP-array- and sequencing-based methods rely largely on single genomic features and indirect transformations to estimate this fraction. We developed BaySeq-Y, a Bayesian method that directly estimates LOY mosaicism from sequencing data using VCF files with read depth (DP) and allelic depth (AD). Within a rigorous Bayesian framework, BaySeq-Y integrates complementary LOY-associated genomic features, including decreased read depth and allelic imbalance, and can additionally leverage haplotype phasing to improve precision. In simulations and fluorescence in situ hybridization validation (FISH), BaySeq-Y provided accurate estimates and outperformed existing methods. Applications to ROSMAP and GTEx supported its biological relevance through transcriptomic validation, demonstrating its utility for quantifying LOY across diverse sequencing datasets.

bioinformatics↗

bioRxiv2026

HSPB8 regulates CTP synthase filaments to couple nucleotide metabolism and autophagy in tumors

Metabolic adaptation and proteostasis are essential for tumor survival under nutrient stress, yet how these processes are mechanistically integrated remains unclear. Here, we identify CTP synthase (CTPS) filament dynamics as a regulatory nexus linking nucleotide metabolism to autophagic flux. Under glutamine deprivation--a hallmark of poorly vascularized solid tumors--CTPS undergoes polymerization into filamentous assemblies that exhibit reduced enzymatic activity. We demonstrate that filament formation is driven by intracellular asparagine availability and stabilized by the accumulation of misfolded proteins. Using APEX2-based proximity labeling and proteomics, we identify the small heat shock protein HSPB8 as a filament-associated regulator. HSPB8, acting within the chaperone-assisted selective autophagy (CASA) pathway, antagonizes CTPS polymerization by promoting clearance of misfolded proteins, thereby restoring soluble, catalytically active CTPS. Filament disassembly increases CTP production and enhances synthesis of autophagy-related phospholipids, including phosphatidylinositol and phosphatidylethanolamine, resulting in accelerated autophagic flux. Cells expressing filament-deficient CTPS mutants display elevated autophagosome formation and increased LC3-II accumulation upon lysosomal blockade, confirming enhanced flux. In vivo, disruption of CTPS filament assembly impairs xenograft tumor growth and is associated with excessive autophagy. Analysis of TCGA datasets further reveals that high CTPS and low HSPB8 expression correlate with poor patient survival across multiple cancers. Collectively, our findings establish CTPS filament dynamics as a proteostasis-sensitive metabolic switch that coordinates nucleotide biosynthesis with autophagy, revealing a previously unrecognized vulnerability in tumors adapting to nutrient limitation.

cell biology↗

bioRxiv2026

Deficiency of miR130a leads to fat hypertrophy, hepatic steatosis, insulin resistance and glucose intolerance in mice

Insulin resistance, excessive and ectopic fat accumulation, chronic low-grade inflammation, and pancreatic beta-cell failure are pathological features of type 2 diabetes mellitus.MiR-130a has been demonstrated to suppress the mRNA levels of PPAR{gamma}, NF-{kappa}B, and TNF- in vitro. PPAR{gamma} is a master regulator of systemic fat and glucose metabolism. NF-{kappa}B and TNF- are pivotal modulators of inflammation. Therefore, we aimed to examine the systemic effect of miR130a on fat metabolism, glucose/insulin homeostasis, and inflammation in mice. We found that mirR130a-deficient mice exhibited larger white fat mass with hypertrophic adipocytes, increased lipogenic gene expression in fat, and elevated serum leptin levels than controls. The white fat pads of mirR130a-deficient mice showed significant macrophage infiltration with enhanced expression of pro-inflammatory genes. In addition, mirR130a-deficient mice had more severe hepatic steatosis and higher hepatic triglycerides content than controls. Similarly, mirR130a-deficient mice had increased macrophage infiltration and lipogenic and inflammatory gene expression in the liver. Consistently, we found that Lepob/ob mice expressed markedly decreased miR130a expression in the liver and white fat compared to controls. Importantly, mirR130a-deficient mice displayed impaired glucose tolerance and worsened insulin resistance, accompanied with reduced serum adiponectin levels. Furthermore, insulin secretion is reduced in mirR130a-deficient mice compared to controls. In conclusion, knockout of miR130a in mice results in fat hypertrophy, hepatic steatosis, increased macrophage infiltration in liver and fat, glucose intolerance, and insulin resistance. These data indicate miR130a exert systemic anti-diabetic effects.

molecular biology↗

bioRxiv2025

Chemical proteomics decrypts the kinases that shape the dynamic human phosphoproteome

Mass-spectrometry-based phosphoproteomics enables the analysis of thousands of protein phosphorylation events across the human proteome. However, there is a lack of scalable, hypothesis-free, and statistically sound approaches for discovering, evaluating, and falsifying kinase::substrate relationships (KSRs). Here, we developed a new concept termed potency-coherence analysis. By measuring and integrating 17 million peptidoform-specific dose-response curves for 133 kinase inhibitors with known targets and affinities, we could critically re-evaluate published KSRs and discover thousands of potency-coherent and motif-plausible new KSRs for 96 human kinases. Application of these high-confidence KSRs enabled the estimation of kinase and signaling pathway activities in cancer patient biopsies. This unified and extendable framework has been implemented in ProteomicsDB to aid researchers in understanding the human phosphoproteome in health and disease.

systems biology↗

bioRxiv2025

TRIB2 couples UCP1 degradation to thermogenic adaptation and metabolic health

Genetic variation in TRIB2 has been associated with thermogenesis and fat accumulation, yet the underlying molecular mechanisms remain unclear. Uncoupling protein 1 (UCP1) is a key regulator of adaptive thermogenesis and energy expenditure. Here, we identified a human TRIB2 variant associated with migration patterns along latitude and environmental temperature, which destabilized its mRNA and is consistent with enhanced thermogenic capacity. We demonstrate that loss of Trib2 protects mice from diet-induced obesity, alleviates hepatic steatosis, and improves glucose tolerance and insulin sensitivity. Trib2 knockout mice exhibit elevated UCP1 expression in brown adipose tissue, leading to enhanced thermogenesis and increased heat production. Mechanistically, TRIB2 acts as a scaffold that binds UCP1 through its pseudokinase domain and recruits the E3 ligase MYCBP2, thereby promoting UCP1 ubiquitination and proteasomal degradation. Collectively, our findings reveal a previously unrecognized post-translational mechanism that regulates UCP1 stability and link TRIB2 function to both thermogenic adaptation and metabolic health, thereby highlighting TRIB2 as a potential therapeutic target for obesity and metabolic disorders.

molecular biology↗

bioRxiv2025

A Yeast-Based High-Throughput Screening Platform for the Discovery of Novel pre-mRNA Splicing Modulators

Pre-mRNA splicing is a crucial process in eukaryotic gene expression, and splicing dysregulation has been linked to various diseases. However, very few small molecules have been discovered that can modulate spliced mRNA formation or inhibit the splicing machinery itself. This study presents a novel high-throughput screening (HTS) platform for identifying compounds that modulate splicing. Our platform comprises a two-tiered screening approach: a primary screen measuring growth inhibition in sensitized in S. cerevisiae (yeast) strains and a secondary screen that relies on production of a fluorescent protein as a readout for splicing inhibition. Using this approach, we identified 4 small molecules that cause accumulation of unspliced pre-mRNA in vivo in yeast. In addition, cancer cells expressing a myelodysplastic syndrome-associated splicing factor mutation (SRSF2P95H) are more sensitive to one of these compounds than those expressing the wild-type version of the protein. Transcriptome analyses showed that this compound causes widespread changes in gene expression in sensitive SRSF2P95H-expressing cells. Our results demonstrate the utility of using a yeast-based HTS to identify compounds capable of changing pre-mRNA splicing outcomes.

biochemistry↗

bioRxiv2025

Loss of PIMREG impairs double-strand break signaling and repair

Glioblastoma (GBM) is the most common primary brain tumor in adults. It is an aggressive type of tumor with an average overall survival of 12-15 months post-diagnosis. Standard treatment involves surgical resection, followed by radiotherapy and chemotherapy with temozolomide (TMZ). However, resistance to treatment is frequently observed. PIMREG is a marker of proliferation highly expressed across different tumor types, with particularly elevated levels in GBM. Our previous study revealed that PIMREG silencing sensitizes GBM cells to TMZ treatment and affects ATM activation, a key apical kinase involved in DNA damage signaling. Given the emerging significance of PIMREG in the DNA damage response, we sought to explore PIMREGs role in DNA damage repair and signaling in GBM cells exposed to genotoxic agents. Here we assessed the functionally enriched pathways associated with high PIMREG expression in GBM patient samples, analyzed the interactome of PIMREG upon treatment of GBM cells with TMZ and evaluated the impact of PIMREG loss on DNA damage signaling, DNA break formation and the repair of double-strand breaks. Our findings reveal that PIMREG functions as a direct substrate for ATM/ATR kinases, interacts with key DNA repair proteins upon TMZ treatment and actively facilitates the cellular response to chemotherapy- and radiotherapy-induced DNA damage. Taken together, PIMREG may function in the DNA damage response, particularly in the signaling and repair of double strand breaks via homologous recombination in GBM cells. In all, our data suggested high PIMREG expression may affect resistance of GBM cells to treatment.

cancer biology↗

bioRxiv2025

Hypoxia-induced metastatic heterogeneity in pancreatic cancer

In most solid tumors, hypoxia constitutes a defining microenvironmental feature that reprograms malignant cells into a highly metastatic state by driving cellular plasticity and exacerbating chromosomal instability (CIN). However, the mechanisms by which cancer cells concurrently co-opt these elements of hypoxic adaptation to promote metastasis remains poorly understood. Here, we report that hypoxia promotes metastasis by suppressing the JmjC-containing histone lysine demethylase Kdm8. CRISPR/Cas9-mediated targeting of Kdm8 in a Kras;Trp53-driven mouse model of pancreatic ductal adenocarcinoma (PDA) robustly rewires the malignant cell transcriptomic programs, leading to a profound loss of the epithelial morphology and widespread metastatic disease. In PDA patients, a high KDM8-induced gene signature is associated with reduced metastatic burden and better survival in advanced disease. Notably, Kdm8 suppression in normoxia recapitulates key aspects of the global epigenetic and transcriptomic rewiring, mitotic spindle defects, and CIN induced by hypoxia. Moreover, disruption of Kdm8s demethylase activity phenocopies Kdm8 loss, whereas expression of hypermorphic Kdm8 variants resistant to hypoxic suppression markedly reduces metastasis beyond the levels achieved by the wildtype protein. Through the suppression of Kdm8 demethylase function, hypoxia unleashes a potent metastatic program by simultaneously advancing cellular plasticity and CIN.

cell biology↗

bioRxiv2025

Contribution of HMGB1 to Keratinocyte inflammation in Recessive Dystrophic Epidermolysis Bullosa

Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited skin disorder characterized by fragile skin, blistering, and chronic wounds. Keratinocytes, the primary cells in the epidermis, are directly affected by persistent injury in RDEB, contributing to chronic inflammation. High mobility group box 1 (HMGB1) is elevated in the serum of individuals with RDEB. However, its role in keratinocyte inflammation remains unclear. Here, we report an increase in HMGB1 expression in keratinocytes at chronic wound sites compared to matched non-wounded skin from an RDEB individual, suggesting a potential link to local inflammation. Pharmacological inhibition of HMGB1 using inflachromene reduced lipopolysaccharide (LPS)-induced inflammatory responses in a keratinocyte cell line, supporting a role for keratinocyte-specific HMGB1 in inflammation. Surprisingly, deletion of HMGB1 alone or together with its paralogue HMGB2 did not suppress the inflammatory response to LPS. Furthermore, inflachromene still reduced inflammation in these knockout cells. This unexpected discrepancy between genetic deletion and pharmacologic inhibition points to a more complex role for HMGB1 or off-target effects of the compound. These findings suggest that HMGB1 may contribute to inflammation in keratinocytes, but its exact function needs further investigation.

molecular biology↗

bioRxiv2025

Forecast Padding Enhances Accuracy and Robustness of EEG-Phase-Synchronized TMS

Closed-loop neuromodulation is a promising personalized treatment for various neuropsychiatric disor-ders, delivering precise stimuli based on real-time brain signals. However, its clinical potential is currently limited by technical challenges inherent in its real-time nature. This article addresses the primary technical challenges in EEG-Phase-Synchronized Transcranial Magnetic Stimulation (TMS), including poor stimulation accuracy and inefficient biomarker detection (correlated with deadlock). These challenges arise from the vulnerability of existing algorithms to filter edge effects. Inspired by predictive coding theory in neuroscience, we propose a novel signal padding method (forecast padding) to mitigate the filter edge effect. To properly quantify the improvements that forecast padding brings about in real-world systems, we introduce a novel delay-relevant validation framework and demonstrate its reliability using experimental data from a real system. Through this framework, we demonstrate that forecast padding significantly improves both stimulation accuracy and deadlock rate. Given the pervasive impact of filter edge effects in closed-loop neuromodulation and other signal processing domains, forecast padding shows broad application potential across various fields.

bioengineering↗

bioRxiv2025

Accessory subunits of PRC2 mimic H3K27me3 to restrict the spread of Polycomb domains

The Polycomb repressive complex 2 (PRC2) is essential for normal development by maintaining developmental gene repression. PRC2 deposits the repressive chromatin mark H3 lysine 27 tri-methyl (H3K27me3) through a read-write loop that involves direct interactions between PRC2 and H3K27me3. According to current models, the PRC2-H3K27me3 read-write loop is initiated by the PRC2 subunits JARID2 and PALI1 that mimic H3K27me3. However, it is unknown what restricts the PRC2-H3K27me3 read-write loop from spreading H3K27me3 indefinitely. To answer this question, we generated mutant mice where PRC2 subunits cannot mimic H3K27me3. Unexpectedly, the mutations led to delayed Hox genes activation and a homeotic transformation characteristic of a Polycomb gain-of-function in vivo and the spread of H3K27me3 beyond Polycomb domains in stem cells. Collectively, we show that H3K27me3 mimicry evolved to compete against the PRC2-H3K27me3 read-write loop in a process that restrains PRC2 and restricts the spread of Polycomb domains. HighlightsO_LIH3K27me3 mimicry antagonises Polycomb function in vivo. C_LIO_LIJARID2 and PALI1 synergise to allosterically regulate PRC2 during development. C_LIO_LIH3K27me3 mimicry by JARID2 and PALI1 antagonises PRC2 in stem cells. C_LIO_LIJARID2 and PALI1 mimic H3K27me3 to restrict the spread of Polycomb domains. C_LI

molecular biology↗

bioRxiv2025

Hyperglycemia-Driven Hepatic Immune Dysfunction Facilitates Microbial Dissemination Post-Myocardial Infarction

BackgroundThe gut microbiome is intimately connected to cardiovascular health through the gut-heart axis and plays a pivotal role in maintaining homeostasis. Myocardial infarction (MI) disrupts this homeostatic balance, leading to widespread adverse effects. Hyperglycemia, a hallmark of metabolic dysfunction, further exacerbates these disruptions, emphasizing the need to understand the underlying mechanisms to develop effective therapeutic strategies for mitigating the cascading complications along the gut-heart axis. This study aims to elucidate the dynamics of gut barrier disruption during MI, and explore the livers function as an immune sentinel in this process, with a focus on the impact of hyperglycemia on microbial dissemination, systemic inflammation, and liver immune function. MethodsA murine MI model was used to evaluate gut permeability, bacterial translocation, and hepatic immune responses. MI was induced via permanent left anterior descending artery ligation. Hyperglycemia was established through streptozotocin injections and a high-fat, high-sugar diet. Gut barrier integrity was assessed using FITC-dextran assays, and microbial translocation was tracked through intravital imaging and anaerobic bacterial cultures from multiple organs. Hepatic immune function was analyzed via flow cytometry, cytokine profiling, and phagocytosis assays. 16S rRNA sequencing characterized the composition of translocated bacteria. ResultsMI significantly increased intestinal permeability, with hyperglycemia further exacerbating gut barrier dysfunction. Intravital imaging revealed bacterial translocation through the portal vein to the liver, highlighting the livers role in microbial interception. Hyperglycemia impaired hepatic macrophage function by activating NLRP3 inflammasome signaling, reducing bacterial clearance and promoting persistent liver colonization. Systemic inflammatory cytokines, particularly TNF-, were elevated, further facilitating microbial dissemination. 16S rRNA sequencing demonstrated host-dependent stochastic variability in translocated bacterial composition. ConclusionThe liver serves as a key immune regulator in the gut-liver-heart axis but is functionally compromised under hyperglycemia, exacerbating systemic inflammation and microbial dissemination post-MI. Targeting NLRP3 signaling and restoring gut barrier integrity may mitigate post-MI complications, particularly in hyperglycemic conditions. These findings underscore the need for integrated therapeutic strategies incorporating metabolic control and microbiome-targeted interventions to improve post-MI outcomes.

immunology↗

bioRxiv2025

Illuminating oncogenic KRAS signaling by multi-dimensional chemical proteomics

Mutated KRAS is among the most frequent activating genetic alterations in cancer and drug discovery efforts have led to inhibitors that block its activity. To better understand oncogenic KRAS signaling and the cytostatic effects of drugs, we performed comprehensive dose-dependent proteome-wide target deconvolution, pathway engagement and protein expression characterization of KRAS, MEK, ERK, SHP2 and SOS1 inhibitors in pancreatic (KRAS G12C, G12D) and lung cancer (KRAS G12C) cells. Analysis of the resulting 687,954 dose-response curves available online revealed both common and cell line-specific signaling networks dominated by oncogenic KRAS activity. Time-dose experiments separated early KRAS-MEK-ERK from CDK-mediated signaling that cause cells to exit from the cell cycle. This transition to a quiescent state occurred without substantial proteome re-modelling but extensive changes of protein phosphorylation and ubiquitylation. The collective data highlights the complexity of KRAS signaling in cancer and places a large number of new proteins into this functional context.

cell biology↗

bioRxiv2025

Structural basis of K11/K48-branched ubiquitin chain recognition by the human 26S proteasome

Beyond the canonical K48-linked homotypic polyubiquitination for proteasome-targeted proteolysis, K11/K48-branched ubiquitin (Ub) chains are involved in fast-tracking protein turnover during cell cycle progression and proteotoxic stress. Here, we report cryo-EM structures of human 26S proteasome in a complex with a K11/K48-branched Ub chain. The structures revealed a multivalent substrate recognition mechanism involving a hitherto unknown K11-linked Ub binding site at the groove formed by RPN2 and RPN10 in addition to the canonical K48-linkage binding site formed by RPN10 and RPT4/5 coiled-coil. Additionally, RPN2 recognizes an alternating K11-K48 linkage through a conserved motif similar to the K48-specific T1 binding site of RPN1. The insights gleaned from these structures explain the molecular mechanism underlying the recognition of the K11/K48 branched Ub as a priority signal in the ubiquitin-mediated proteasomal degradation.

biochemistry↗

bioRxiv2024

Identification of PTGR2 inhibitors as a new therapy for diabetes and obesity

Peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) is a master transcriptional regulator of systemic insulin sensitivity and energy balance. The anti-diabetic drug thiazolidinediones (TZDs) are potent synthetic PPAR{gamma} ligands with undesirable side effects, including obesity, fluid retention, and osteoporosis. 15-keto prostaglandin E2 (15-keto-PGE2) is an endogenous PPAR{gamma} ligand metabolized by prostaglandin reductase 2 (PTGR2). Here, we confirmed that 15-keto-PGE2 binds and activates PPAR{gamma} via covalent binding. In patients with type 2 diabetes and obese mice, serum 15-keto-PGE2 levels were decreased. Administration of 15-keto-PGE2 improves glucose homeostasis and prevented diet-induced obesity in mice. Either genetic inhibition of PTGR2 or PTGR2 inhibitor BPRPT0245 protected mice from diet-induced obesity, insulin resistance, and hepatic steatosis without fluid retention and osteoporosis. In conclusion, inhibition of PTGR2 is a new therapeutic approach to treat diabetes and obesity through increasing endogenous PPAR{gamma} ligands without side effects of synthetic PPAR{gamma} ligands TZDs.

physiology↗

bioRxiv2024

Identification of a novel mycovirus belonging to the ''flexivirus''-related family with icosahedral virion

The order Tymovirales currently comprises five viral families with positive-sense RNA ((+)RNA) genomes that infect plants, fungi, and insects. Virion morphologies within the order Tymovirales differ between families, with icosahedral virions in the Tymoviridae and filamentous virions in the other "flexi"viridae families. Despite their different morphologies, these viruses are placed in the same order based on phylogenetic analyses of replicase-associated polyproteins. However, one of the families in the Tymovirales, Deltaflexiviridae, is considered to be capsidless because there have been no published reports of virion isolation. Here we report that a new "flexivirus"-related (+)RNA virus, prospectively named Fusarium oxysporum icosahedral virus 1 (FoIV1), is icosahedral, and that most deltaflexiviruses may have icosahedral virions. Phylogenetic analyses based on replicase-associated polyproteins indicated that FoIV1 forms a distinct group in the Tymovirales with some viruses originally assigned to the Deltaflexiviridae. Electron microscopy, protein analysis, and protein structure predictions indicate that FoIV1 ORF4 encodes a single jelly-roll (SJR)-like coat protein (CP) that constitutes the icosahedral virions. Results of clustering analyses based on amino acid sequences and predicted CP structures suggested that most of the deltaflexiviruses have icosahedral virions composed of SJR-like CPs as in FoIV1, rather than having filamentous virions or capsidless. These results challenge the conventional understanding of viruses in the order Tymovirales, with important implications for revising its taxonomic framework and providing insights into the evolutionary relationships within this diverse and broad host range group of (+)RNA viruses.

microbiology↗