Biology subjects

Keszei, Z.

Publications and source records attributed to Keszei, Z..

3 recordsLinked to original sources

bioRxiv2026

Gut-derived ammonia modulates hypothalamic stress responses during viral infection

The gut-brain axis integrates microbial and host metabolism to regulate systemic physiology, yet its role during viral infection remains poorly defined. Viral infection induces behavioral changes and neuroendocrine stress responses accompanied by profound alterations in gut microbial metabolism. Here, we show that chronic viral infection in mice increases systemic levels of microbiota-derived ammonia in a CD8 T cell-dependent manner. Increased ammonia accumulates in the brain and selectively activates neurons within the paraventricular hypothalamus (PVH), driving corticosterone release into the circulation. Pharmacological inhibition of ammonia detoxification exacerbates these effects, leading to increased corticosterone levels, aggravated sickness behavior, and dampened antiviral responses. Together, these findings identify gut-derived ammonia as a previously unrecognized immunometabolic signal linking antiviral T cell responses to hypothalamic control of systemic stress during viral infection. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=186 SRC="FIGDIR/small/736796v1_ufig1.gif" ALT="Figure 1"> View larger version (59K): org.highwire.dtl.DTLVardef@1291dbcorg.highwire.dtl.DTLVardef@5f223corg.highwire.dtl.DTLVardef@1c0aafaorg.highwire.dtl.DTLVardef@190502_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2025

Crosstalk between CD8+ T cells and systemic bile acid metabolism controls LCMV-induced immunopathology

Antiviral immunity has a profound effect on host metabolism, which can, in turn, modulate immune responses and influences disease pathology. Among its many functions, the liver orchestrates systemic bile acid (BA) metabolism, a pathway disrupted in chronic liver diseases such as viral hepatitis. BAs have become increasingly recognized for their immunomodulatory properties, and multiple BA species are being explored as therapeutic agents in liver diseases. Understanding the interplay between immune responses and BA metabolism could unlock new therapeutic opportunities based on BA modulation. Using lymphocytic choriomeningitis virus (LCMV) as a model, we investigated the interplay between chronic hepatotropic virus infection, BA metabolism and immunity. Our findings reveal that chronic LCMV infection increases BA levels and shifts circulating and liver BA composition towards host-derived, conjugated BAs. At the same time, hepatic BA transport and synthesis genes are broadly downregulated, which is at least partially dependent on CD8+ T cells. Additionally, we found that sustained high BA levels impact CD8+ T cell responses to chronic LCMV infection. Mice with elevated circulating BAs due to the lack of BA transporters OATP1a and OATP1b, showed impaired T cell expansion and reduced liver immunopathology. These findings reveal a reciprocal interplay between CD8+ T cells and BA metabolism, expanding our understanding of adaptive immunity against viral hepatitis. Moreover, it highlights how immuno-metabolic changes in liver disease may affect the bodys ability to fight infections and cancer. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=170 SRC="FIGDIR/small/670599v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@7d4bcorg.highwire.dtl.DTLVardef@1f84b5org.highwire.dtl.DTLVardef@1419686org.highwire.dtl.DTLVardef@1014b8c_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2020

Mutational dynamics and transmission properties of SARS-CoV-2 superspreading events in Austria

Superspreading events shape the COVID-19 pandemic. Here we provide a national-scale analysis of SARS-CoV-2 outbreaks in Austria, a country that played a major role for virus transmission across Europe and beyond. Capitalizing on a national epidemiological surveillance system, we performed deep whole-genome sequencing of virus isolates from 576 samples to cover major Austrian SARS-CoV-2 clusters. Our data chart a map of early viral spreading in Europe, including the path from low-frequency mutations to fixation. Detailed epidemiological surveys enabled us to calculate the effective SARS-CoV-2 population bottlenecks during transmission and unveil time-resolved intra-patient viral quasispecies dynamics. This study demonstrates the power of integrating deep viral genome sequencing and epidemiological data to better understand how SARS-CoV-2 spreads through populations. Graphical Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

microbiology↗