Curr Neurovasc Res. 2023 Jul 3. doi: 10.2174/1567202620666230703122140. Online ahead of print.

ABSTRACT

BACKGROUND: Autoimmune diseases are associated with cardiovascular and cerebrovascular diseases. However, whether myasthenia gravis (MG) and ischemic stroke (IS) are causally related remains unclear.

OBJECTIVE: This study aimed to evaluate potential causal links between MG and IS using bidirectional Mendelian randomization (MR).

METHODS: We conducted a two-sample MR analysis to assess the potential associations between MG and IS. Genetic variants associated with MG and IS as well as their subtypes were extracted from genome-wide association studies by meta-analysis. The inverse-variance weighted method was used for the main MR analysis. Sensitivity analyses, including the MREgger, simple mode, simple median, weighted mode, and weighted median approaches were applied to test the robustness of the results.

RESULTS: The MR analyses indicated no causal effects of general MG on IS of all causes (odds ratio [OR] = 0.990, 95% confidence interval [CI]: 0.953-1.029, P = 0.615), large vessel atherosclerosis stroke (OR = 0.943, 95% CI: 0.856-1.039, P = 0.233), cardioembolic stroke (OR = 0.975, 95% CI: 0.867-1.096, P = 0.670), and small vessel occlusion stroke (OR = 1.059, 95% CI 0.974-1.150, P = 0.178). Subgroup analyses indicated no causal effects of early- or late-onset MG on IS and its subtypes (all P > 0.05). The reverse MR analysis showed no significant causal associations of IS on MG (all P > 0.05).

CONCLUSION: Bidirectional MR analysis did not provide evidence to support a causal relationship between genetically predicted MG and IS, although observational studies have found such a potential link.

PMID:37403387 | DOI:10.2174/1567202620666230703122140

Biophys J. 2023 Jul 4:S0006-3495(23)00411-3. doi: 10.1016/j.bpj.2023.06.023. Online ahead of print.

ABSTRACT

Bacterial cells that stop growing but maintain viability and the capability to regrow are termed dormant and have been shown to transiently tolerate high concentrations of antimicrobials. Links between tolerance and cellular energetics as a possible explanation for the tolerance, have been investigated and have produced mixed and seemingly contradictory results. Because dormancy merely indicates growth arrest, which can be induced by various stimuli, we hypothesise that dormant cells may exist in a range of energetic states that depend on the environment. To energetically characterise different dormancies, we first induce them in a way that results in dormant populations and subsequently measured both of their main energy sources, the PMF magnitude and the concentration of ATP. We find that different types of dormancy exhibit characteristic energetic profiles that vary in level and dynamics. The energetic makeup was associated with survival to some antibiotics, but not others. Our findings portray dormancy as a state that is rich in phenotypes with various stress survival capabilities. Because environmental conditions outside of the lab often halt or limit microbial growth, a typologisation of dormant states may yield relevant insights on the survival and evolutionary strategies of these organisms.

PMID:37403359 | DOI:10.1016/j.bpj.2023.06.023

Plant Commun. 2023 Jul 4:100645. doi: 10.1016/j.xplc.2023.100645. Online ahead of print.

ABSTRACT

Understanding plant immune responses is complex due to the high interdependence among biological processes in homeostatic networks. Hence, the integration of environmental cues causes network rewiring that interferes with defence responses. Similarly, plants retain molecular signatures configured under abiotic stress periods to rapidly respond to recurrent stress that can alter immunity. Metabolome changes imposed by abiotic stressors are persistent, although the impact on defence is elusive. In this study, we profiled metabolomes of Arabidopsis plants under several abiotic stress treatments applied individually or simultaneously to capture temporal trajectories in metabolite composition during adverse conditions and recovery. Further systemic analysis was conducted to address the relevance of metabolome changes and extract central features to be tested in planta. Our results demonstrate irreversibility in major fractions of metabolome changes as a general pattern in response to abiotic stress periods. Functional analysis of metabolomes and co-abundance networks points to convergences in the reconfiguration of the metabolism of organic acids and secondary metabolites. Arabidopsis mutant lines for components related to these metabolic pathways displayed altered defence capacities against different pathogens. Collectively, our data support that sustained metabolome changes configured during adverse environments can act as modulators of immune responses and provide evidence for a new layer of regulation in plant defence.

PMID:37403356 | DOI:10.1016/j.xplc.2023.100645

Traffic. 2023 Jul 4. doi: 10.1111/tra.12908. Online ahead of print.

ABSTRACT

Each cell in a multicellular organism permanently adjusts the concentration of its cell surface proteins. In particular, epithelial cells tightly control the number of carriers, transporters and cell adhesion proteins at their plasma membrane. However, sensitively measuring the cell surface concentration of a particular protein of interest in live cells and in real time represents a considerable challenge. Here, we introduce a novel approach based on split luciferases, which uses one luciferase fragment as a tag on the protein of interest and the second fragment as a supplement to the extracellular medium. Once the protein of interest arrives at the cell surface, the luciferase fragments complement and generate luminescence. We compared the performance of split Gaussia luciferase and split Nanoluciferase by using a system to synchronize biosynthetic trafficking with conditional aggregation domains. The best results were achieved with split Nanoluciferase, for which luminescence increased more than 6000-fold upon recombination. Furthermore, we showed that our approach can separately detect and quantify the arrival of membrane proteins at the apical and basolateral plasma membrane in single polarized epithelial cells by detecting the luminescence signals with a microscope, thus opening novel avenues for characterizing the variations in trafficking in individual epithelial cells.

PMID:37403269 | DOI:10.1111/tra.12908

Mol Cell. 2023 Jun 28:S1097-2765(23)00461-6. doi: 10.1016/j.molcel.2023.06.016. Online ahead of print.

ABSTRACT

Insertions and deletions (indels) are common sources of structural variation, and insertions originating from spontaneous DNA lesions are frequent in cancer. We developed a highly sensitive assay called insertion and deletion sequencing (Indel-seq) to monitor rearrangements in human cells at the TRIM37 acceptor locus that reports indels stemming from experimentally induced and spontaneous genome instability. Templated insertions, which derive from sequences genome wide, require contact between donor and acceptor loci, require homologous recombination, and are stimulated by DNA end-processing. Insertions are facilitated by transcription and involve a DNA/RNA hybrid intermediate. Indel-seq reveals that insertions are generated via multiple pathways. The broken acceptor site anneals with a resected DNA break or invades the displaced strand of a transcription bubble or R-loop, followed by DNA synthesis, displacement, and then ligation by non-homologous end joining. Our studies identify transcription-coupled insertions as a critical source of spontaneous genome instability that is distinct from cut-and-paste events.

PMID:37402370 | DOI:10.1016/j.molcel.2023.06.016

Mol Cell. 2023 Jun 27:S1097-2765(23)00434-3. doi: 10.1016/j.molcel.2023.06.012. Online ahead of print.

ABSTRACT

Transcription factors (TFs) orchestrate the gene expression programs that define each cell's identity. The canonical TF accomplishes this with two domains, one that binds specific DNA sequences and the other that binds protein coactivators or corepressors. We find that at least half of TFs also bind RNA, doing so through a previously unrecognized domain with sequence and functional features analogous to the arginine-rich motif of the HIV transcriptional activator Tat. RNA binding contributes to TF function by promoting the dynamic association between DNA, RNA, and TF on chromatin. TF-RNA interactions are a conserved feature important for vertebrate development and disrupted in disease. We propose that the ability to bind DNA, RNA, and protein is a general property of many TFs and is fundamental to their gene regulatory function.

PMID:37402367 | DOI:10.1016/j.molcel.2023.06.012

J Leukoc Biol. 2023 Jul 4:qiad076. doi: 10.1093/jleuko/qiad076. Online ahead of print.

ABSTRACT

The differentiation and activation of macrophages are critical regulatory programs that are central to host inflammation and defense against pathogens. However, the transcriptional regulatory pathways involved in these programs are not well understood. Herein, we demonstrate that the activity and expression of Activating Transcription Factor 2 (ATF2) is precisely regulated during primary human monocyte to macrophage differentiation, and that its activation is linked to M1 polarization and antibacterial responses. Genetic perturbation experiments demonstrated that deletion of ATF2 (THP-ΔATF2) resulted in irregular and abnormal macrophage morphology, whereas macrophages overexpressing ATF2 (THP-ATF2) developed round and pancake-like morphology, resembling classically activated (M1) macrophages. Mechanistically, we show that ATF2 binds to the core promoter of PPM1A, a phosphatase that regulates monocyte-to-macrophage differentiation, to regulate its expression. Functionally, overexpression of ATF2 sensitized macrophages to M1 polarization, resulting in increased production of MHC Class II, IL-1β and IP-10, improved phagocytic capacity, and enhanced control of the intracellular pathogen Mycobacterium tuberculosis. Gene expression profiling revealed that overexpression of ATF2 reprogramed macrophages to promote antibacterial pathways enriched in chemokine signaling, metabolism and antigen presentation. Consistent with pathways analysis, metabolic profiling revealed that genetic overexpression or stimuli-induced activation of ATF2 alters the metabolic capacity of macrophages and primes these cells for glycolytic metabolism during M1 polarization or bacterial infection. Our findings reveal that ATF2 plays a central role during macrophage differentiation and M1 polarization to enhance the functional capacities of macrophages.

PMID:37403209 | DOI:10.1093/jleuko/qiad076

BMC Bioinformatics. 2023 Jul 4;24(1):275. doi: 10.1186/s12859-023-05400-2.

ABSTRACT

BACKGROUND: P4 medicine (predict, prevent, personalize, and participate) is a new approach to diagnosing and predicting diseases on a patient-by-patient basis. For the prevention and treatment of diseases, prediction plays a fundamental role. One of the intelligent strategies is the design of deep learning models that can predict the state of the disease using gene expression data.

RESULTS: We create an autoencoder deep learning model called DeeP4med, including a Classifier and a Transferor that predicts cancer's gene expression (mRNA) matrix from its matched normal sample and vice versa. The range of the F1 score of the model, depending on tissue type in the Classifier, is from 0.935 to 0.999 and in Transferor from 0.944 to 0.999. The accuracy of DeeP4med for tissue and disease classification was 0.986 and 0.992, respectively, which performed better compared to seven classic machine learning models (Support Vector Classifier, Logistic Regression, Linear Discriminant Analysis, Naive Bayes, Decision Tree, Random Forest, K Nearest Neighbors).

CONCLUSIONS: Based on the idea of DeeP4med, by having the gene expression matrix of a normal tissue, we can predict its tumor gene expression matrix and, in this way, find effective genes in transforming a normal tissue into a tumor tissue. Results of Differentially Expressed Genes (DEGs) and enrichment analysis on the predicted matrices for 13 types of cancer showed a good correlation with the literature and biological databases. This led that by using the gene expression matrix, to train the model with features of each person in a normal and cancer state, this model could predict diagnosis based on gene expression data from healthy tissue and be used to identify possible therapeutic interventions for those patients.

PMID:37403016 | DOI:10.1186/s12859-023-05400-2

Nat Commun. 2023 Jul 4;14(1):3936. doi: 10.1038/s41467-023-38747-4.

ABSTRACT

Circular RNAs (circRNAs) are a regulatory RNA class. While cancer-driving functions have been identified for single circRNAs, how they modulate gene expression in cancer is not well understood. We investigate circRNA expression in the pediatric malignancy, neuroblastoma, through deep whole-transcriptome sequencing in 104 primary neuroblastomas covering all risk groups. We demonstrate that MYCN amplification, which defines a subset of high-risk cases, causes globally suppressed circRNA biogenesis directly dependent on the DHX9 RNA helicase. We detect similar mechanisms in shaping circRNA expression in the pediatric cancer medulloblastoma implying a general MYCN effect. Comparisons to other cancers identify 25 circRNAs that are specifically upregulated in neuroblastoma, including circARID1A. Transcribed from the ARID1A tumor suppressor gene, circARID1A promotes cell growth and survival, mediated by direct interaction with the KHSRP RNA-binding protein. Our study highlights the importance of MYCN regulating circRNAs in cancer and identifies molecular mechanisms, which explain their contribution to neuroblastoma pathogenesis.

PMID:37402719 | DOI:10.1038/s41467-023-38747-4

Cell Death Discov. 2023 Jul 4;9(1):223. doi: 10.1038/s41420-023-01468-0.

NO ABSTRACT

PMID:37402715 | DOI:10.1038/s41420-023-01468-0

Bioinformatics. 2023 Jul 4:btad397. doi: 10.1093/bioinformatics/btad397. Online ahead of print.

ABSTRACT

MOTIVATION: One central goal of systems biology is to infer biochemical regulations from large-scale OMICS data. Many aspects of cellular physiology and organismal phenotypes can be understood as results of metabolic interaction network dynamics. Previously, we have proposed a convenient mathematical method which addresses this problem using metabolomics data for the inverse calculation of biochemical Jacobian matrices revealing regulatory checkpoints of biochemical regulations. The proposed algorithms for this inference are limited by two issues: they rely on structural network information that needs to be assembled manually, and they are numerically unstable due to ill-conditioned regression problems for large-scale metabolic networks.

RESULTS: To address these problems we developed a novel regression-loss based inverse Jacobian algorithm, combining metabolomics COVariance and genome-scale metabolic RECONstruction, which allows for a fully automated, algorithmic implementation of the COVRECON workflow. It consists of two parts: a, Sim-Network and b, Inverse differential Jacobian evaluation. Sim-Network automatically generates an organism-specific enzyme and reaction dataset from Bigg and KEGG databases, which is then used to reconstruct the Jacobian's structure for a specific metabolomics dataset. Instead of directly solving a regression problem as in the previous workflow, the new inverse differential Jacobian is based on a substantially more robust approach and rates the biochemical interactions according to their relevance from large-scale metabolomics data.The approach is illustrated by in silico stochastic analysis with differently-sized metabolic networks from the BioModels database and applied to a real-world example. The characteristics of the COVRECON implementation are that i) it automatically reconstructs a data-driven superpathway model; ii) more general network structures can be investigated and iii) the new inverse algorithm improves stability, decreases computation time, and extends to large-scale models.

AVAILABILITY: The code is available in the website https://bitbucket.org/mosys-univie/covrecon.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:37402625 | DOI:10.1093/bioinformatics/btad397

Anim Cogn. 2023 Jul 4. doi: 10.1007/s10071-023-01806-w. Online ahead of print.

ABSTRACT

Animal vocalisations encode a wide range of biological information about the age, sex, body size, and social status of the emitter. Moreover, vocalisations play a significant role in signalling the identity of the emitter to conspecifics. Recent studies have shown that, in the African penguin (Spheniscus demersus), acoustic cues to individual identity are encoded in the fundamental frequency (F0) and resonance frequencies (formants) of the vocal tract. However, although penguins are known to produce vocalisations where F0 and formants vary among individuals, it remains to be tested whether the receivers can perceive and use such information in the individual recognition process. In this study, using the Habituation-Dishabituation (HD) paradigm, we tested the hypothesis that penguins perceive and respond to a shift of ± 20% (corresponding to the natural inter-individual variation observed in ex-situ colonies) of F0 and formant dispersion (ΔF) of species-specific calls. We found that penguins were more likely to look rapidly and for longer at the source of the sound when F0 and formants of the calls were manipulated, indicating that they could perceive variations of these parameters in the vocal signals. Our findings provide the first experimental evidence that, in the African penguin, listeners can perceive changes in F0 and formants, which can be used by the receiver as potential cues for the individual discrimination of the emitter.

PMID:37401990 | DOI:10.1007/s10071-023-01806-w

Sheng Wu Gong Cheng Xue Bao. 2023 Jun 25;39(6):2101-2107. doi: 10.13345/j.cjb.230386.

ABSTRACT

Engineering efficient enzymes or microbial cell factories should help to establish green bio-manufacturing process for chemical overproduction. The rapid advances and development in synthetic biology, systems biology and enzymatic engineering accerleate the establishing feasbile bioprocess for chemical biosynthesis, including expanding the chemical kingdom and improving the productivity. To consolidate the latest advances in chemical biosynthesis and promote green bio-manufaturing, we organized a special issue on chemical bioproduction that including review or original research papers about enzymatic biosynthesis, cell factory, one-carbon based biorefinery and feasible strategies. These papers comprehensively discussed the latest advaces, the challenges as well as the possible solutions in chemical biomanufacturing.

PMID:37401584 | DOI:10.13345/j.cjb.230386

Gut Microbes. 2023 Jan-Dec;15(1):2229945. doi: 10.1080/19490976.2023.2229945.

ABSTRACT

Inflammatory bowel disease (IBD) is a multifactorial disease with increasing incidence in the U.S. suggesting that environmental factors, including diet, are involved. It has been suggested that excessive consumption of linoleic acid (LA, C18:2 omega-6), which must be obtained from the diet, may promote the development of IBD in humans. To demonstrate a causal link between LA and IBD, we show that a high fat diet (HFD) based on soybean oil (SO), which is comprised of ~55% LA, increases susceptibility to colitis in several models, including IBD-susceptible IL10 knockout mice. This effect was not observed with low-LA HFDs derived from genetically modified soybean oil or olive oil. The conventional SO HFD causes classical IBD symptoms including immune dysfunction, increased intestinal epithelial barrier permeability, and disruption of the balance of isoforms from the IBD susceptibility gene Hepatocyte Nuclear Factor 4α (HNF4α). The SO HFD causes gut dysbiosis, including increased abundance of an endogenous adherent invasive Escherichia coli (AIEC), which can use LA as a carbon source. Metabolomic analysis shows that in the mouse gut, even in the absence of bacteria, the presence of soybean oil increases levels of LA, oxylipins and prostaglandins. Many compounds in the endocannabinoid system, which are protective against IBD, are decreased by SO both in vivo and in vitro. These results indicate that a high LA diet increases susceptibility to colitis via microbial and host-initiated pathways involving alterations in the balance of bioactive metabolites of omega-6 and omega-3 polyunsaturated fatty acids, as well as HNF4α isoforms.

PMID:37400966 | DOI:10.1080/19490976.2023.2229945

bioRxiv. 2023 Jun 19:2023.06.01.543292. doi: 10.1101/2023.06.01.543292. Preprint.

ABSTRACT

Antibodies are critical reagents to detect and characterize human proteins. The biomedical research community aspires to have at least one potent and selective renewable antibody for each human protein, and for each of the most common applications. To quantify progress toward this goal, a standardized characterization approach to assess the performance of 614 commercial antibodies for 65 neuroscience-related proteins in Western blot, immunoprecipitation, and immunofluorescence applications, using isogenic knockout cells as controls. Side-by-side comparisons of the antibodies demonstrated that: i) for each application tested, approximately half of this protein set was covered by at least one high-performing antibody, suggesting that coverage of human proteins by commercial antibodies is significant but gaps are still present; ii) on average recombinant antibodies performed better than monoclonal or polyclonal antibodies; iii) hundreds of underperforming antibodies have been used in published articles. Encouragingly, more than half of the commercial antibodies that did not perform as expected were removed from the market by manufacturers or had alterations made to their recommended usage based on this body of work. This work suggests an efficient strategy toward achieving coverage of the human proteome with selective renewable antibodies is to mine the existing commercial antibody repertoire, using this knowledge to focus new renewable antibody generation efforts.

PMID:37398479 | PMC:PMC10312534 | DOI:10.1101/2023.06.01.543292

Nat Immunol. 2023 Jul 3. doi: 10.1038/s41590-023-01548-4. Online ahead of print.

ABSTRACT

Innate lymphoid cells (ILCs) can quickly switch from a quiescent state to an active state and rapidly produce effector molecules that provide critical early immune protection. How the post-transcriptional machinery processes different stimuli and initiates robust gene expression in ILCs is poorly understood. Here, we show that deletion of the N6-methyladenosine (m6A) writer protein METTL3 has little impact on ILC homeostasis or cytokine-induced ILC1 or ILC3 responses but significantly diminishes ILC2 proliferation, migration and effector cytokine production and results in impaired antihelminth immunity. m6A RNA modification supports an increase in cell size and transcriptional activity in activated ILC2s but not in ILC1s or ILC3s. Among other transcripts, the gene encoding the transcription factor GATA3 is highly m6A methylated in ILC2s. Targeted m6A demethylation destabilizes nascent Gata3 mRNA and abolishes the upregulation of GATA3 and ILC2 activation. Our study suggests a lineage-specific requirement of m6A for ILC2 responses.

PMID:37400674 | DOI:10.1038/s41590-023-01548-4

Nat Methods. 2023 Jul 3. doi: 10.1038/s41592-023-01915-x. Online ahead of print.

ABSTRACT

An unambiguous description of an experiment, and the subsequent biological observation, is vital for accurate data interpretation. Minimum information guidelines define the fundamental complement of data that can support an unambiguous conclusion based on experimental observations. We present the Minimum Information About Disorder Experiments (MIADE) guidelines to define the parameters required for the wider scientific community to understand the findings of an experiment studying the structural properties of intrinsically disordered regions (IDRs). MIADE guidelines provide recommendations for data producers to describe the results of their experiments at source, for curators to annotate experimental data to community resources and for database developers maintaining community resources to disseminate the data. The MIADE guidelines will improve the interpretability of experimental results for data consumers, facilitate direct data submission, simplify data curation, improve data exchange among repositories and standardize the dissemination of the key metadata on an IDR experiment by IDR data sources.

PMID:37400558 | DOI:10.1038/s41592-023-01915-x

Nat Biotechnol. 2023 Jul 3. doi: 10.1038/s41587-023-01830-8. Online ahead of print.

ABSTRACT

Transcriptome engineering applications in living cells with RNA-targeting CRISPR effectors depend on accurate prediction of on-target activity and off-target avoidance. Here we design and test ~200,000 RfxCas13d guide RNAs targeting essential genes in human cells with systematically designed mismatches and insertions and deletions (indels). We find that mismatches and indels have a position- and context-dependent impact on Cas13d activity, and mismatches that result in G-U wobble pairings are better tolerated than other single-base mismatches. Using this large-scale dataset, we train a convolutional neural network that we term targeted inhibition of gene expression via gRNA design (TIGER) to predict efficacy from guide sequence and context. TIGER outperforms the existing models at predicting on-target and off-target activity on our dataset and published datasets. We show that TIGER scoring combined with specific mismatches yields the first general framework to modulate transcript expression, enabling the use of RNA-targeting CRISPRs to precisely control gene dosage.

PMID:37400521 | DOI:10.1038/s41587-023-01830-8

Adv Sci (Weinh). 2023 Jul 3:e2302611. doi: 10.1002/advs.202302611. Online ahead of print.

ABSTRACT

Lymphangioleiomyomatosis (LAM) is a rare disease involving cystic lung destruction by invasive LAM cells. These cells harbor loss-of-function mutations in TSC2, conferring hyperactive mTORC1 signaling. Here, tissue engineering tools are employed to model LAM and identify new therapeutic candidates. Biomimetic hydrogel culture of LAM cells is found to recapitulate the molecular and phenotypic characteristics of human disease more faithfully than culture on plastic. A 3D drug screen is conducted, identifying histone deacetylase (HDAC) inhibitors as anti-invasive agents that are also selectively cytotoxic toward TSC2-/- cells. The anti-invasive effects of HDAC inhibitors are independent of genotype, while selective cell death is mTORC1-dependent and mediated by apoptosis. Genotype-selective cytotoxicity is seen exclusively in hydrogel culture due to potentiated differential mTORC1 signaling, a feature that is abrogated in cell culture on plastic. Importantly, HDAC inhibitors block invasion and selectively eradicate LAM cells in vivo in zebrafish xenografts. These findings demonstrate that tissue-engineered disease modeling exposes a physiologically relevant therapeutic vulnerability that would be otherwise missed by conventional culture on plastic. This work substantiates HDAC inhibitors as possible therapeutic candidates for the treatment of patients with LAM and requires further study.

PMID:37400371 | DOI:10.1002/advs.202302611

Phytopathology. 2023 Jul 3. doi: 10.1094/PHYTO-12-22-0465-V. Online ahead of print.

ABSTRACT

High-throughput sequencing (HTS) and sequence mining tools revolutionized virus detection and discovery in recent years and implementing them with classical plant virology techniques results to a powerful approach to characterize viruses. An example of a virus discovered through HTS is Solanum nigrum ilarvirus 1 (SnIV1) (Bromoviridae), which was recently reported in various solanaceous plants from France, Slovenia, Greece, and South Africa. It was likewise detected in grapevines (Vitaceae) and several Fabaceae and Rosaceae plant species. Such very diverse set of source organisms is atypical for ilarviruses, thus warranting further investigation. In this study, modern and classical virological tools were combined to accelerate the characterization of SnIV1. Through HTS-based virome surveys, mining of sequence read archive datasets, and literature search, SnIV1 was further identified from diverse plant and non-plant sources globally. SnIV1 isolates showed relatively low variability compared to other phylogenetically related ilarviruses. Phylogenetic analyses showed a distinct basal clade of isolates from Europe, while the rest formed clades of mixed geographic origin. Furthermore, systemic infection of SnIV1 in Solanum villosum and its mechanical and graft transmissibility to solanaceous species were demonstrated. Near identical SnIV1 genomes from the inoculum (S. villosum) and inoculated Nicotiana benthamiana were sequenced, thus partially fulfilling Koch's postulates. SnIV1 was shown to be seed-transmitted and potentially pollen-borne, has spherical virions, and possibly induces histopathological changes in infected N. benthamiana leaf tissues. Overall, this study provides information to better understand the diversity, global presence, and pathobiology of SnIV1, however, its possible emergence as a destructive pathogen remains uncertain.

PMID:37399026 | DOI:10.1094/PHYTO-12-22-0465-V