bioRxiv Science⌕ Search

bioRxiv · 10.1101/404657

Tenuivirus uses a molecular bridge strategy to overcome insect midgut barriers for virus persistent transmission

Abstract

Many persistent transmitted plant viruses, including Rice stripe tenuivirus (RSV), cause serious damages to crop productions in China and worldwide. Although many reports have indicated that successful insect-mediated virus transmission depends on proper virus-insect vector interactions, the mechanism(s) controlling interactions between viruses and insect vectors for virus persistent transmission remained poorly understood. In this study, we used RSV and its small brown planthopper (SBPH) vector as a working model to elucidate the molecular mechanism controlling RSV virion entrance into SBPH midgut for persistent transmission. We have now demonstrated that this non-enveloped Tenuivirus uses its non-structural glycoprotein NSvc2 as a helper component to bridge the specific interaction between virion and SBPH midgut cells, leading to overcome SBPH midgut barriers for virus persistent transmission. In the absence of this glycoprotein, purified RSV virion is not capable of entering SBPH midgut cells. In RSV-infected cells, glycoprotein NSvc2 is processed into two mature proteins: an amino-terminal protein NSvc2-N and a carboxyl-terminal protein NSvc2-C. We determined that NSvc2-N interacted with RSV virion and bound directly to midgut lumen surface via its N-glycosylation sites. Upon recognition by midgut cells, the midgut cells underwent endocytosis followed by compartmentalizing RSV virion and NSvc2 into early and then late endosomes. The acidic condition inside the late endosome triggered conformation change of NSvc2-C and caused cell membrane fusion via its highly conserved fusion loop motifs, leading to the release of RSV virion from endosome into cytosol. In summary, our results showed for the first time that a rice Tenuivirus uses a molecular bridge strategy to ensure proper interactions between virus and insect midgut for successful persistent transmission.\n\nAuthor summaryOver 75% of the known plant viruses are insect transmitted. Understanding how plant viruses interacted with their insect vectors during virus transmission is one of the key steps to manage virus diseases worldwide. Both the direct and indirect virus-insect vector interaction models have been proposed for virus non-persistent and semi-persistent transmission. However, the indirect virus-vector interaction mechanism during virus persistent transmission has not been reported previously. In this study, we developed a new reverse genetics technology and demonstrated that the circulative and propagative transmitted Rice stripe tenuivirus utilizes a glycoprotein NSvc2 as a helper component to ensure a specific interaction between Tenuivirus virion and midgut cells of small brown planthopper (SBPH), leading to conquering the midgut barrier of SBPH. This is the first report of a helper component mediated-molecular bridge mechanism for virus persistent transmission. These new findings and our new model on persistent transmission expand our understanding of molecular mechanism(s) controlling virus-insect vector interactions during virus transmission in nature.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Lu, G., Li, S., Zhou, C., Qian, X., Xiang, Q., Yang, T., Wu, J., Zhou, X., Zhou, Y., Ding, X. S., Tao, X.. 2018-08-30. Tenuivirus uses a molecular bridge strategy to overcome insect midgut barriers for virus persistent transmission. https://doi.org/10.1101/404657

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Biomechanical stress in the retinal pigment epithelium surrounding laser scars in humans

Purpose : The wound response of an epithelium comprises tissue-scale activation of stress fibers whose contraction regionally reconfigures the epithelium and drives closure of the wound. Recent in vitro studies have shown that similar biomechanical processes can paradoxically lead to enlargement of epithelial holes. In patients having undergone laser photocoagulation of the retinal pigment epithelium (RPE), laser scars may expand over years. Here, to document the implication of epithelial biomechanics in the enlargement of laser scars we analyzed the dynamic changes affecting the RPE around scars in patients and performed confocal microscopy on a RPE flat-mount from a donor eye. Methods: We analyzed the image files of five patients (age 61 to 85 years) showing enlargement of laser scars in the RPE (follow-up, 13 to 60 months). In three of them, prospective imaging was performed using transscleral illumination adaptive optics ophthalmoscopy (AOO), an imaging technology enabling visualization of RPE cells. Time-lapse sequences were analyzed to track dynamic processes in the RPE surrounding scars. A flat-mounted phalloidin-labeled RPE from a human donor eye with a history of scatter photocoagulation was examined by confocal microscopy to document the distribution of stress fibers and cell metrics. Results: Time-lapse sequences showed that enlargement of laser scars was accompanied by the displacement of microscopic features in margins of atrophy. AOO imaging suggested locally coordinated displacement of mosaic of darks spots, with a generally radial or tangent direction relative to the edges of scars. Such movements were detected up to several hundred microns from the edges of scars. On the histology sample, elongated RPE cells with stress fibers forming actin cables were found along edges of scars, which formed fascicles between adjacent scars. Conclusion: Enlargement of RPE scars may be accompanied by long-lasting, largescale changes in the distribution of microscopic features in the margins of lesions. In particular, transscleral illumination AOO showed coordinated displacement of a mosaic similar to the one described for the RPE. The finding by histology of RPE cell with a tractional phenotype along edges further suggests that epithelial biomechanics contribute to such movements and may hence contribute to scar enlargement.

pathology↗

Loss of stromal VEGFR2 protects against ischemic acute kidney injury by preserving the renal microvasculature

Injury to the renal microvasculature, particularly the peritubular capillaries, is a defining feature of ischemic acute kidney injury (AKI). Vascular endothelial growth factor receptor 2 (VEGFR2) signaling is a central regulator of endothelial cell survival, proliferation, migration, and vascular remodeling. Although VEGFR2 has been extensively studied in endothelial cells, accumulating evidence suggests that it is also expressed in non-endothelial cell populations, where it may regulate tissue-specific responses to injury. Here, using publicly available single-cell or single-nucleus RNA sequencing data from human and mouse kidneys, we identified VEGFR2 expression in renal stromal populations. Immunostaining further detected phosphorylated VEGFR2 in the renal stroma of mouse kidneys. To determine the functional role of stromal VEGFR2, we utilized renal stroma-specific Vegfr2 KO mice. Stromal VegfR2 deletion attenuated kidney injury after renal ischemia/reperfusion injury (IRI), as evidenced by reduced tubular injury, preservation of renal blood flow, decreased endothelial oxidative stress, and maintenance of the renal microvasculature. Stromal Vegfr2-deficient kidneys also exhibited increased Angpt1 and Tek levels, enhanced endothelial ERK activation, and preserved endothelial adherent junctions. Taken together, these findings reveal an unexpected role for VEGFR2 in the renal stromal lineage and highlight stromal-endothelial communication as a potential therapeutic target for preserving microvascular integrity after ischemic AKI.

pathology↗

Digital pathological classification of peripheral neuroblastic tumors across multi-continent cohorts

Peripheral neuroblastic tumors (pNTs) are embryonal tumors of neural crest origin with highly variable clinical behaviors, ranging from spontaneous regression to aggressive and fatal disease. The International Neuroblastoma Pathology Classification (INPC) defines four diagnostic categories and stratifies tumors into Favorable Histology (FH) or Unfavorable Histology (UH) group based on age-linked assessment of tumor differentiation/maturation and the Mitosis-Karyorrhexis Index (MKI). Prognostic distinction according to INPC offers significant prediction of clinical outcomes, with patients harboring FH tumors demonstrating longer overall and event-free survival than those with UH tumor. Here, we assembled the largest multi-continental whole-slide histology imaging dataset of pNTs to date, comprising 2,030 tumors from the United States, Canada, Australia, New Zealand, Germany and Japan. Using this dataset, we developed NB-PathAssist, a computational pathology framework for automated INPC-based classification from digitized whole-slide images. NB-PathAssist integrates foundation-model-based feature extraction with an archetype-guided SummaryMixing architecture that compresses whole-slide morphology into representative histologic tokens for tumor-level classification. To automate MKI assessment, we manually annotated 14,049 nuclei, classifying them as mitotic-karyorrhectic (MK) tumor cells, non-MK tumor cells, or non-tumor cells. The resulting model was applied to phenotype cells in whole-slide images across 1,649 tissue sections. Across geographically and institutionally diverse cohorts, NB-PathAssist reproducibly assessed key diagnostic features and generated prognostic classifications concordant with reference INPC annotations. The average balanced accuracy for classifying tumor categories, grade of neuroblastic differentiation, MKI and prognostic groups achieved 0.84, 0.86, 0.89 and 0.96, respectively. We packaged the NB-PathAssist algorithms into an end-to-end online platform for scalable and standardized AI-assisted assessment of pNTs.

pathology↗