Biology subjects

Lu, S.-C.

Publications and source records attributed to Lu, S.-C..

3 recordsLinked to original sources

bioRxiv2024

Novel Mechanism of Inflammatory Activation by Ebola Virus Matrix Protein Linked to the Ebolavirus Virulence

Uncontrolled systemic inflammatory responses are a critical pathological feature of fatal Ebola virus (EBOV) infection. While some inflammatory responses may originate from mononuclear phagocytes (MNPs), non-immune cells vastly outnumber MNPs and may be an important source of inflammation. Here, we demonstrated that highly virulent EBOV induced a high and sustained pro-inflammatory response compared to less virulent ebolaviruses in non-MNPs through TLR4-independent NF-{kappa}B activation. We identified the EBOV matrix protein VP40 as a potent activator of NF-{kappa}B in non-MNPs, whose intrinsic inflammatory activation ability is higher than VP40 proteins from less virulent ebolaviruses. This suggests that VP40 is a novel virulence determinant inducing distinct degrees of pro-inflammatory responses among ebolaviruses. Mechanistically, VP40 activated the NF-{kappa}B signaling pathway, primarily via TNFR1 using a ligand-independent mechanism. These findings reveal mechanisms that may drive systemic inflammation and promote EBOV pathogenesis, suggesting potential therapeutic strategies to mitigate immune dysregulation in severe EBOV infections.

microbiology↗

bioRxiv2023

Evaluating the validity of the eye movement event detection model of Ganzin Sol glasses

Eye tracking requires precise measurement of gaze data. Identifying fixations and saccades reliably is crucial for eye trackers, given these are fundamental eye movements. The present study evaluated the performance of Ganzin Sol glasses, a wearable eye tracker developed by Ganzin Technology, in detecting eye movement events. Participants performed the fixation and saccade invocation task (Komogortsev et al., 2010) and the gap paradigm (Saslow, 1967) using both Ganzin Sol and Tobii Pro 2 glasses separately at both short (50 cm) and long (300 cm) viewing distance. The fixation and saccade invocation task involved maintaining fixation on a regularly shifting visual target, enabling quantitative and qualitative analysis of participants oculomotor behaviors. In the gap paradigm, participants executed saccades toward a peripheral target when the fixation disappeared (gap condition) or remained visible (overlap condition). Typically, saccade latency in the gap condition is shorter (i.e., the gap effect). Results revealed aligned performances with Ganzin Sol and Tobii Pro 2 glasses in the fixation and saccade invocation task and the observation of the gap effect with both eye trackers. Therefore, the validity of Ganzin Sol glasses was at least comparable to Tobii Pro 2 glasses in the present study.

neuroscience↗

bioRxiv2021

Ex Vivo and In Vivo CD46 Receptor Utilization by Species D Human Adenovirus Serotype 26 (HAdV26)

Human adenovirus serotype 26 (Ad26) is used as a gene-based vaccine against SARS-CoV-2 and HIV-1. Yet, its primary receptor portfolio remains controversial, potentially including sialic acid, CAR, integrins, and CD46. We and others have shown that Ad26 can use CD46, but these observations were questioned by the inability to co-crystallize Ad26 fiber with CD46. Recent work demonstrated that Ad26 binds CD46 with its hexon protein rather than its fiber. We examined the functional consequences of Ad26 for infection in vitro and in vivo. Ectopic expression of human CD46 on Chinese hamster ovary cells increased Ad26 infection significantly. Deletion of the complement control protein domains CCP1 or CCP2 or the serine-threonine-proline (STP) region of CD46 reduced infection. Comparing wild type and sialic acid-deficient CHO cells, we show that the usage of CD46 is independent of its sialylation status. Ad26 transduction was increased in CD46 transgenic mice after intramuscular (IM) injection, but not after intranasal (IN) administration. Ad26 transduction was 10-fold lower than Ad5 after intratumoral (IT) injection of CD46-expressing tumors. Ad26 transduction of liver was 1000-fold lower than Ad5 after intravenous (IV) injection. These data demonstrate the use of CD46 by Ad26 under certain situations, but also show that the receptor has little consequence by other routes of administration. Finally, IV injection of high doses of Ad26 into CD46 mice induced release of liver enzymes in the bloodstream and reduced white blood cell counts, but did not induce thrombocytopenia. This suggests that Ad26 virions do not induce direct clotting side effects seen during COVID-19 vaccination with this serotype of adenovirus. IMPORTANCEHuman species D Ad26 is being pursued as a low seroprevalence vector for oncolytic virotherapy and gene-based vaccination against HIV-1 and SARS-CoV-2. However, there is debate in the literature about its tropism and receptor utilization, which directly influence its efficiency for certain applications. This work was aimed at determining which receptor(s) this virus uses for infection, and its role in virus biology, vaccine efficacy, and importantly, in vaccine safety.

pharmacology and toxicology↗