Biology subjects

Schultz-Pernice, I.

Publications and source records attributed to Schultz-Pernice, I..

3 recordsLinked to original sources

bioRxiv2025

Bemnifosbuvir and remdesivir inhibit tick-borne encephalitis virus infection in complementary in vitro and ex vivo disease models

The geographical distribution and incidence of tick-borne encephalitis (TBE) have steeply increased over the past decades, raising to represent a major health concern in Asia and Europe. Symptoms of TBE, caused by infections with tick-borne encephalitis virus (TBEV), range from mild, flu-like symptoms to severe neurological disease, often accompanied by long-term sequelae persisting for several years following pathogen encounter. While effective vaccines against TBEV are available, no antiviral drugs are currently approved and therapeutic options for patients suffering from TBE are limited to supportive measures. Compounds able to disrupt viral nucleic acid synthesis bear the potential of effectively limiting viral replication and spread. Seeking to fill the therapeutic gap, we evaluated the efficacy of a panel of approved and investigational antiviral compounds in containing TBEV infection. Combining several cell lines, human neural organoids and organotypic rat brain slice cultures, we found that the nucleoside analogs remdesivir and bemnifosbuvir efficiently limit viral replication. Through infectious virus quantification, immunofluorescence analysis and flow cytometry, we report significant, dose-dependent reduction of viral loads across all models used, with inhibition observed at low doses for both drugs. Notably, while we observed bemnifosbuvir to be well tolerated, we report important cytotoxicity of remdesivir when applied to human neural organoids. Our findings identify bemnifosbuvir and remdesivir as novel treatment strategies for TBE, providing an accessible and timely response to a clinical challenge of pressing concern.

microbiology↗

bioRxiv2023

Mpox virus spreads from cell-to-cell and leads to neuronal injury in human cerebral organoids

In 2022-23, the world experienced the largest recorded monkeypox virus (MPXV) outbreak outside of endemic regions. Remarkably, cases of neurological manifestations were reported, some of which fatal. MPXV DNA and MPXV-specific antibodies were detected in the cerebrospinal fluid of encephalitis-affected patients, suggesting neuroinvasive potential of MPXV. We explored the susceptibility of neural tissue to MPXV infection using human neural organoids (hNOs) exposed to a primary isolate belonging to clade IIb lineage. The virus efficiently replicates in hNOs as indicated by the exponential increase of infectious viral loads and the elevated frequency of MPXV-positive cells over time. Electron microscopy imaging revealed the presence of viral particles as well as perinuclear viral factories. We observed susceptibility of several cell types to the virus, including neural progenitor cells and neurons. Furthermore, we detected the presence of viral antigen in neurites and in foci of grouped cells distributed throughout the tissue. In line with this, we documented significantly more cell-associated than released infectious virus, suggesting viral spread by cell-to-cell contact. Using an mNeonGreen-expressing recombinant MPXV, we confirmed cell-associated virus transmission through live-cell imaging. While hNOs displayed no evident outer morphological changes upon infection, we detected the formation of beads in neurites, a phenomenon commonly associated with neurodegenerative disorders. Live-cell imaging further confirmed the recurrent formation of neuritic beads in neurons in the days following MPXV infection, with bead formation preceding neurite-initiated cell death. Notably, treatment of MPXV infected hNOs with the antiviral drug tecovirimat resulted in a significant reduction of infectious viral loads by several orders of magnitude. Taken together, our findings suggest viral manipulation of axonal transport driving neuronal degeneration and identify a mechanism potentially contributing to MPXV-mediated neuropathology that may have therapeutic implications.

microbiology↗

bioRxiv2020

Transcriptional changes in the mammary gland during lactation revealed by single cell sequencing of cells from human milk

Findings from epidemiological studies suggest that breast cancer risk is influenced by parity in an age-dependent manner. However, human mammary tissue remodelling that takes place during pregnancy and lactation remain little understood due to the challenge of acquiring samples. Here, we present an approach to overcome this using single-cell RNA sequencing to examine viable primary mammary epithelial cells isolated from human milk compared to resting, non-lactating breast tissue. Thereby, we determined that separate to breast tissue, human milk largely contains epithelial cells belonging to the luminal lineage, as well as immune cells. Our data reveal the presence of two distinct secretory luminal cell clusters in milk which highly express luminal progenitor signatures akin to non-lactating breast tissue luminal cells. Taking advantage of the fact that both the resting and lactating mammary gland contain a luminal compartment, we focussed on comparing these transcriptomes and identified differences in mammary cell function and metabolism between these maturation states. These findings provide the basis to dissect human luminal differentiation and milk biosynthesis pathways that in the future, may be interrogated to determine how parity influences luminal cell metabolism and breast cancer risk.

cell biology↗