Biology subjects

Genger, J.-W.

Publications and source records attributed to Genger, J.-W..

7 recordsLinked to original sources

bioRxiv2026

Suitable seasons: Global monthly habitat suitability for the arbovirus vectors Aedes aegypti and Aedes albopictus in 1975-2024

The mosquito species Aedes aegypti and Aedes albopictus are the primary vectors of the arboviruses dengue, Zika, and chikungunya. Expansion of these vectors into previously non-endemic regions due to climate and environmental changes has accelerated global burden from arboviral diseases. To combat this, predictive models accurately mapping Aedes habitats are essential for epidemiological modelling, effective vector control, and disease prevention. We introduce the Climademic Suitability Model, a machine learning model that delivers monthly global predictions of Aedes habitat suitability at 0.25{degrees} spatial resolution between 1975--2024. The model leverages integrated climate, land use, human population, and mosquito surveillance data to provide an explainable view of the factors governing habitat dynamics. SHAP-based explainability analysis identified temperature and dew point temperature as dominant features driving habitat suitability. Long-term analysis reveals a complex global redistribution of expanding and contracting vector habitats. Suitable areas for both species now encompass regions home to over 5 billion people, coinciding with the worlds most pronounced population growth and surpassing projections previously placing this threshold at 2050. The Climademic Suitability Model serves as a framework for near-real-time vector surveillance, climate scenario projection, and integration into transmission models to advance epidemic preparedness in an era of accelerating environmental change.

ecology↗

bioRxiv2025

CD8+ T cells regulate the bioenergetic reprogramming of lymphoid organs and the heart during viral infection

The activation of the immune system is a bioenergetically-costly process1. Yet, essential bodily functions require a continuous energy supply, imposing energy constraints and trade-offs between competing processes2. Our understanding of the underlying bioenergetic adaptations reconciling rapid immune activation with other vital processes remains scarce. 3-6 Here, by using experimental models of viral infections, we identified an unexpected CD8+ T cell-driven redistribution of energy substrates between lymphoid organs and the heart. Viral infection promoted systemic hypoglycaemia and ketogenesis, together with systemic reallocation of energy substrates. Across organs analysed, secondary lymphoid organs and the heart showed the most dramatic changes. The former increased glucose uptake and oxidation while the heart showed the opposite, switching to preferential fatty acid utilization. These bioenergetic adaptations were absent in infected mice lacking CD8+ T cells or with T cells lacking the glucose transporter GLUT1. Pharmacological inhibition of fatty acid oxidation forced a systemic switch to glucose oxidation. This was associated with metabolic decompensation, reduced cardiac energetics, left ventricular stress, and mortality in otherwise nonlethal viral infections. Our results reveal how the energetic cost of immune cell activation imposes bioenergetic adaptations on non-lymphoid organs, posing a major challenge for the heart by completely relying on fatty acids.

immunology↗

bioRxiv2025

Purine nucleobases enhance CD8+ T cell effector function

During antiviral immune responses, activated immune cells remodel metabolic pathways towards uptake and utilization of biosynthetic and bioenergetic metabolites. Concurrently, viral infections alter metabolic environments, impacting metabolite availability for the establishment of an effective immune response. Here, we integrated in vivo metabolomics data from murine and human viral infections with in vitro metabolite screens, identifying purine nucleobases as novel immunometabolites that enhance CD8+ T cell effector function. We found that CD8+ T cells can switch from resource-intensive purine de novo synthesis to purine salvage pathway, to produce nucleotides from purine nucleobases. This strategy of metabolic adaptation allows diversion of biosynthetic and bioenergetic resources towards enhancing effector molecule production. Our findings unveil an adaptation strategy by CD8+ T cells to manage metabolic challenges in dynamic organismal environments and suggest pharmacological targets in purine metabolism as potential targets for immunotherapy. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=144 SRC="FIGDIR/small/669899v1_ufig1.gif" ALT="Figure 1"> View larger version (65K): org.highwire.dtl.DTLVardef@17b4b15org.highwire.dtl.DTLVardef@17e57a3org.highwire.dtl.DTLVardef@1abc36aorg.highwire.dtl.DTLVardef@1aa704a_HPS_FORMAT_FIGEXP M_FIG C_FIG Instead of producing nucleotides via purine de novo synthesis, CD8+ T cells can import and utilize purine nucleobases via the purine salvage pathway to divert bioenergetic and biosynthetic resources towards effector function. By shifting from purine de novo synthesis to the purine salvage pathway, cells save significant resources: 5 moles of the key bioenergetic metabolite ATP, and biosynthetic metabolites including 2 moles of glutamine, 1 mole each of serine or glycine, and 1 mole of aspartate.

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↗

bioRxiv2025

Functional profiling reveals a non-enzymatic role of NUDT5 in repressing purine de novo synthesis

Folate metabolism is intricately linked to purine de novo synthesis through the incorporation of folate-derived one-carbon units into the purine scaffold. Here, we investigate the chemical and genetic dependencies caused by mutations in the folate enzyme MTHFD1 and discover a key role for Nudix hydrolase 5 (NUDT5) in regulating purine de novo synthesis. Through genetic knockout and development of a selective chemical NUDT5 degrader, we uncover an unprecedented scaffolding role rather than NUDT5 enzymatic activity is responsible for this phenotype. We find that NUDT5 interacts with the rate-limiting enzyme of purine de novo synthesis, PPAT, to repress the pathway in response to elevated purine levels. Our findings establish NUDT5 as an important regulator of purine de novo synthesis and elucidate its role in mediating sensitivities to 6-thioguanine in cancer treatment and to adenosine in MTHFD1 deficiency.

molecular biology↗

bioRxiv2020

SARS-CoV-2 escapes CD8 T cell surveillance via mutations in MHC-I restricted epitopes

CD8+ T cell immunity to SARS-CoV-2 has been implicated in COVID-19 severity and virus control, though direct evidence has been lacking so far. Here, we identified non-synonymous mutations in MHC-I restricted CD8+ T cell epitopes after deep sequencing of 747 SARS-CoV- 2 virus isolates. Mutant peptides exhibited diminished or abrogated MHC-I binding, which was associated with a loss of recognition and functional responses by CD8+ T cells isolated from HLA-matched COVID-19 patients. Our findings highlight the capacity of SARS-CoV-2 to subvert CD8+ T cell surveillance through escape mutations in MHCI-restricted viral epitopes. This provides evolutionary evidence for CD8+ T cell immunity controlling SARS-CoV-2 with consequences for COVID-19 vaccine design.

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↗