Biology subjects

Wendt, L.

Publications and source records attributed to Wendt, L..

4 recordsLinked to original sources

bioRxiv2026

CD81 is an Ebola virus inhibiting factor that is antagonized by GP and VP40

Viruses manipulate the host cell membrane of infected cells for evasion of antiviral immunity, prevention of superinfection and optimization of viral replication and spread. The Ebola virus glycoprotein (EBOV GP) mediates virus entry, but is also known as important factor for subversion of the hosts antiviral immune response. We characterized the dysregulation of cell surface-residing proteins by EBOV GP and found that among several membrane proteins GP interferes with the tetraspanins CD81, CD63 and CD9. This was a conserved function of several filoviral GPs and not observable for viral glycoproteins of other virus families. While CD63 and CD9 were largely dispensable for EBOV replication, CD81 suppressed virus-like particle entry and replication at multiple steps. This phenotype might be explainable by sustained suppression of NF{kappa}B by CD81, that is otherwise activated by VP40 and EBOV trVLP replication. We further demonstrate that not only GP but also VP40 interferes with CD81 functionality and that antibody-mediated clustering of CD81 suppresses EBOV infection. Altogether, the tetraspanin CD81 emerges as druggable NF{kappa}B and EBOV-inhibiting factor, supporting an important role of NF{kappa}B in EBOV replication and potentially virus-induced immunopathogenesis. HighlightsO_LIEBOV GP and VP40 interfere with CD81 cell surface expression C_LIO_LICD81 suppresses NF{kappa}B signaling which is activated by VP40 C_LIO_LICD81 restricts EBOV VLP uptake and replication C_LIO_LITargeting CD81 by a crosslinking antibody inhibits EBOV infection C_LI

microbiology↗

bioRxiv2023

Nucleocapsid condensation drives Ebola viral factory maturation and dispersion

Replication and genome encapsidation of many negative-sense RNA viruses take place in virus-induced membrane-less organelles termed viral factories (VFs). While liquid properties of VFs are believed to control the transition from genome replication to encapsidation, the nucleocapsid assembly, VF maturation and interactions with the cellular environment remain elusive. Here we apply in situ cryo-correlative light and electron tomography to follow nucleocapsid assembly and changes in VF morphology and their liquid properties during Ebola virus infection. We show that Ebola viral nucleocapsids transition from loosely packed helical assemblies in early VFs to condensed cylinders that arrange into highly organized parallel bundles later in infection. Early VFs associate with intermediate filaments and are devoid of other host material, but become progressively accessible to cellular components. Our data suggest that this process is coupled to VF solidification and dispersion, and that changes in liquid properties of VFs promote nucleocapsid transport to budding sites. Highlights- Cryo-ET reveals the molecular architecture of Ebola virus replication compartments - Loosely coiled nucleocapsids transition to condensed cylinders forming bundles - Nucleocapsid condensation drives dispersion of viral factories promoting viral egress - Intermediate filaments associate with and are critical for virus factory formation

microbiology↗

bioRxiv2022

Deep learning-based automated lesion segmentation on mouse stroke magnetic resonance images

Magnetic resonance imaging (MRI) is widely used for ischemic stroke lesion detection in mice. A challenge is that lesion segmentation often relies on manual tracing by trained experts, which is labor-intensive, time-consuming, and prone to inter- and intra-rater variability. Here, we present a fully automated ischemic stroke lesion segmentation method for mouse T2-weighted MRI data. As an end-to-end deep learning approach, the automated lesion segmentation requires very little preprocessing and works directly on the raw MRI scans. We randomly split a large dataset of 382 MRI scans into a subset (n = 293) to train the automated lesion segmentation and a subset (n = 89) to evaluate its performance. We compared Dice coefficients and accuracy of lesion volume against manual segmentation, as well as its performance on an independent dataset from an open repository with different imaging characteristics. The automated lesion segmentation produced segmentation masks with a smooth, compact, and realistic appearance that are in high agreement with manual segmentation.

neuroscience↗

bioRxiv2021

Quantifying the inverted U: A meta-analysis of prefrontal dopamine, D1-receptors, and working memory

Dopamine in the prefrontal cortex can be disrupted in human disorders that affect cognitive function such as Parkinsons disease (PD), attention-deficit hyperactivity disorder (ADHD), and schizophrenia. Dopamine has a powerful effect on prefrontal circuits via the D1-type dopamine receptor (D1DR). It has been proposed that prefrontal dopamine has "inverted U-shaped" dynamics, with optimal dopamine and D1DR signaling required for optimal cognitive function. However, the quantitative relationship between prefrontal dopamine and cognitive function is not clear. Here, we conducted a meta-analysis of published manipulations of prefrontal dopamine and the effects on working memory, a high-level executive function in humans, primates, and rodents that involves maintaining and manipulating information over seconds to minutes. We reviewed 646 papers and found that 75 studies met criteria for inclusion. Our quantification of effect sizes for dopamine, D1DRs, and behavior revealed a negative quadratic slope. This is consistent with the proposed inverted U-shape of prefrontal dopamine and D1DRs and working memory performance, explaining 10% of the variance. Of note, the inverted quadratic fit was much stronger for prefrontal D1DRs alone, explaining 26% of the variance, compared to prefrontal dopamine alone, explaining 10% of the variance. Taken together, these data, derived from a variety of manipulations and systems, demonstrate that optimal prefrontal dopamine signalling is linked with higher cognitive function. Our results provide insight into the fundamental dynamics of prefrontal dopamine, which could be useful for pharmacological interventions targeting prefrontal dopaminergic circuits, and into the pathophysiology of human brain disease.

neuroscience↗