Biology subjects

Ritter, B.

Publications and source records attributed to Ritter, B..

5 recordsLinked to original sources

bioRxiv2024

Repression of varicella zoster virus gene expression during quiescent infection in the absence of detectable histone deposition

Varicella zoster virus (VZV) is a human-specific herpesvirus that establishes latency in peripheral neurons. The only transcripts detected in infected human trigeminal ganglia (TG) obtained shortly after death correspond to the VZV latency-associated transcript (VLT) and associated VLT-ORF63 splice variants. In vitro studies showed that VLT-ORF63 is translated into a protein (pVLT-ORF63) that induces VZV transcription. The mechanisms that lead to this restricted gene expression and the transition to lytic replication remain unknown, partly due to the difficulty of working with human neurons. In this study, we addressed whether the neuroblastoma-derived cell line SH-SY5Y could serve as a model to investigate the mechanisms that lead to repression of VZV gene expression followed by reactivation. VZV productively infected differentiated SH-SY5Y (dSH-SY5Y) whereas incubation with acyclovir (ACV) inhibited virus replication and induced a progressive repression of the virus. Upon removal of ACV there was production of viral particles in a subset of cells, while others contained non-replicating VZV genomes and VLT-containing transcripts for at least 20 days post-infection (dpi). Exogenous expression of VLT-ORF63 induced productive infection, suggesting that the non-replicating and repressed genomes remained functional. Interestingly, histone deposition was undetectable at VZV genomes in quiescently infected dSH-SY5Y cells, pointing to a potential novel mechanism leading to VZV repression in this neuronal setting.

microbiology↗

bioRxiv2023

Genetic diversity of the Atacama Desert shrub Huidobria chilensis in the context of geography and climate

Survival in hyperarid deserts is a major challenge for plant life, requiring the development of evolutionary strategies. The Atacama Desert presents harsh conditions such as limited rainfall, crusted soils, high soil salinity, high altitude, and intense solar radiation. These conditions, together with paleoclimatic variability since the past millions of years, have influenced the genetic structure and connectivity of plant populations, resulting in a diverse flora with high endemism. However, the diversification of most lineages appears to be relatively recent, in contrast to proposed age of the Atacama Desert and the onset, evolution and expansion of hyperarid conditions since the Late Oligocene and Early Miocene. A prominent exception is the Atacama paleoendemic Huidobria chilensis (Loasaceae), which is thought to be adapted to such conditions since the Eocene. Still, the environmental limits and thresholds for life in the Atacama remain poorly understood. To investigate the genetic structure in relation to the history of the Atacama Desert, we studied 186 individuals from 11 populations using genotyping-by-sequencing (GBS). Genome-wide single nucleotide polymorphisms (SNPs) were analyzed for population structure and genetic diversity. We identified three genetic clusters corresponding to geographic regions: the coastal region south of Tocopilla, the Coastal Cordillera around Chanaral, and the Copiapo watershed in the south. These clusters as well as genetic diversity were analyzed alongside rainfall, altitude, and landscape data. Although the genetic data generally supports isolation by distance as a major factor for genetic variation between populations, the study also reveals the influence of the topography on the distribution of H. chilensis and highlights the role of hydrologically connected watersheds and rivers in plant migration and colonization. This shapes the species evolutionary trajectory and genetic diversity. Understanding these patterns provides insights into the adaptation and survival strategies of plants in extreme desert environments such as the Atacama.

genetics↗

bioRxiv2023

Viral modulation of type II interferon increases T cell adhesion and virus spread

During primary infection, varicella zoster virus (VZV) infects epithelial cells in the respiratory lymphoid organs and mucosa. Subsequent infection of lymphocytes, T cells in particular, causes primary viremia allowing systemic spread throughout the host, including the skin. This results in the expression of cytokines, including interferons (IFNs) which partly limit primary infection. VZV also spreads from skin keratinocytes to lymphocytes prior to secondary viremia. How VZV infects lymphocytes from epithelial cells while evading the cytokine response has not been fully established. Here, we show that VZV glycoprotein C (gC) binds IFN-{gamma} and modifies its activity. Transcriptomic analysis revealed that gC in combination with IFN-{gamma} increased the expression of a small subset of IFN-stimulated genes (ISGs), including intercellular adhesion molecule 1 (ICAM1), as well as several chemokines and immunomodulatory genes. The higher ICAM1 protein level at the plasma membrane of epithelial cells resulted in lymphocyte function-associated antigen 1 (LFA-1)-dependent T cell adhesion. This gC activity required a stable interaction with IFN-{gamma} and signalling through the IFN-{gamma} receptor. Finally, the presence of gC during infection increased VZV spread from epithelial cells to peripheral blood mononuclear cells. This constitutes the discovery of a novel strategy to modulate the activity of IFN-{gamma}, inducing the expression of a subset of ISGs, leading to enhanced T cell adhesion and virus spread.

microbiology↗

bioRxiv2022

Innate immune response to SARS-1 CoV-2 infection contributes to neuronal damage in human iPSC-derived peripheral neurons

Severe acute respiratory coronavirus 2 (SARS-CoV-2) infection causes neurological disease in some patients suggesting that infection can affect both the peripheral and central nervous system (PNS and CNS, respectively). It is not clear whether the outcome of SARS-CoV-2 infection of PNS and CNS neurons is similar, and which are the key factors that cause neurological disease: SARS-CoV-2 infection or the subsequent immune response. Here, we addressed these questions by infecting human induced-pluripotent stem cell-derived CNS and PNS neurons with the {beta} strain of SARS-CoV-2. Our results show that SARS-CoV-2 infects PNS neurons more efficiently than CNS neurons, despite lower expression levels of angiotensin converting enzyme 2. Infected PNS neurons produced interferon {lambda}1, several interferon stimulated genes and proinflammatory cytokines. They also displayed neurodegenerative-like alterations, as indicated by increased levels of sterile alpha and Toll/interleukin receptor motif-containing protein 1, amyloid precursor protein and -synuclein and lower levels of nicotinamide mononucleotide adenylyltransferase 2 and {beta}-III-tubulin. Interestingly, blockade of the Janus kinase and signal transducer and activator of transcription pathway by Ruxolitinib did not increase SARS-CoV-2 infection, but reduced neurodegeneration, suggesting that an exacerbated neuronal innate immune response contributes to pathogenesis in the PNS.

microbiology↗

bioRxiv2020

Perspectives on the design and performance of upper-limb wearable stimulation devices for stroke survivors with hemiplegia and spasticity

BackgroundVibrotactile stimulation may improve limb function after stroke; however, current studies are limited by the stationary and clinic-based apparatus used to apply this stimulation. A wearable device could provide vibrotactile stimulation in a mobile form factor, enabling further study of this technique. ObjectiveThe aim of this work is twofold: (1) Design and validate a wearable device for stroke survivors that provides vibrotactile stimulation to the upper limb, and (2) Understand features that influence stroke survivors interaction with an upper-limb wearable device. MethodsA vibrotactile glove was designed to apply stimulation to the stroke-affected hand. This device, the vibrotactile stimulation (VTS) Glove, features small electronics, provides hours of stimulation, and has the appearance of a fingerless fitness glove. We performed two studies. In Study 1, sixteen stroke survivors were given the glove and asked to wear it for three hours daily for eight weeks. Usage time, indicating adherence, was calculated by onboard sensors. The device was evaluated using a log of damages and feedback from participants. Self-reported behaviors during glove use were also collected. In Study 2, eight stroke survivors evaluated new device prototypes in a three-round iterative design study. Interviews were used to collect participant feedback as they donned and doffed the prototypes. Task completion time and correctness were measured. Thematic content analysis was used to define actionable design revisions between each round of evaluation and identify key perspectives on design principles. ResultsThe VTS Glove is lightweight, wireless, and durable. Based on Study 1, adherence appears feasible. Each participant recorded over 140 hours wearing the VTS Glove. Participants reported wearing the glove during activities such as church, social events, dining out, and using the computer. However, 69% of participants struggled to extend or insert their fingers to don the device. Our analysis in Study 2 identified six other relevant perspectives from survivors regarding the wearable devices: hand supination is difficult, grip varies without awareness, devices may lead to sweat, separate finger attachments require dexterity, social comfort is perceived as unimportant, and the affected hand is infrequently used. New device designs with revised features (VTS Phalanx, VTS Armband, and VTS Palm) could be donned in an average time of 48 seconds (vs. 5.05 minutes to don the VTS Glove).

bioengineering↗