Max Planck Institute for Infection Biology

Sheeppox virus (SPPV) is a major livestock pathogen causing economic hardship through reduced production and death of vulnerable sheep, with written descriptions of sheeppox-like disease recorded since antiquity. We report 21 novel ancient SPPV genomes spanning the Eurasian steppe Bronze Age (~1,700 BCE) to the Early Modern period in Western Europe, including multiple genomes obtained from medieval parchment. We estimate that major capripoxvirus lineages diverged ~11,500-3,700 years ago, overlapping known translocations and bio-cultural developments in sheep. Our dataset supports SPPV diverging first within the lineage leading to goatpox virus and lumpy skin disease virus, and that known gene inactivation events within SPPV and goatpox virus occur in our earliest SPPV genomes. These findings reveal that the food security of Eurasian communities have been threatened by sheeppox for over 3,700 years, and provide new insights to the genomic evolution and potential host adaptation of sheeppox virus.

Abstract Ancient DNA is a valuable data source for the understanding of our past. However, to effectively interpret this data, it is essential to know the age of the samples from which the DNA is obtained. Although the field of palaeogenomics has been recognised for its robust open data sharing practices, dating information associated with analysed samples is not reported consistently across palaeogenomic studies, nor is it included as metadata in most genetic data repositories. Here, we describe the addition of standardised precise dating information for ancient microbial genomes into the AncientMetagenomeDir metadata repository of published ancient metagenomic samples. This extension currently includes dating information for over 700 ancient microbial genomic datasets, of which 333 are dated using historical, contextual, or stratigraphic methods, and 405 are radiocarbon dated. We quantitatively assess the quality of radiocarbon date reporting and find that, despite established reporting conventions, radiocarbon dating information is often reported inconsistently across ancient metagenomic studies. This new resource provides ancient microbial researchers with standardised dating information that facilitates more accurate and consistent analysis of metagenomic sequencing data. The dataset also highlights the need for greater standardisation of radiocarbon date reporting in original publications in order to allow effective reuse of this and future ancient microbial data.

1 Abstract Parameter estimation is often necessary to inform transmission models of infectious diseases. This estimation requires choosing an observation model that links the model outputs to the observed data. Although potentially consequential, this choice has received little attention in the literature. Here, we aimed to compare eight observation models, including common distributions such as the Poisson, binomial, negative binomial, and normal (equivalent to least-squares estimation). Using Bayesian inference methods, we fit an SIR-like model to daily case reports during the first wave of COVID-19 in Belgium, Finland, Germany, and the UK. We found considerable differences in the log-likelihoods of the observation models, spanning three orders of magnitude between the best and the worst. Compared with the best models, the binomial, Poisson, and normal models received no support due to their rigid variance structures. Additionally, the binomial and Poisson models produced overly narrow prediction and confidence intervals, especially for key parameters such as the basic reproduction number. The other five models—each with a free dispersion parameter scaling the variance to the mean—performed significantly better, with the negative binomial model ranking first in three countries. We conclude that flexible observation models are essential for transmission models to accurately capture all sources of uncertainty.

BackgroundParkinson’s disease is a complex, multifactorial neurodegenerative disorder characterized by aggregation of α-Synuclein into Lewy bodies, with phosphorylation at serine 129 (pSer129), serving as a key regulatory site and pathological hallmark. However, the exact mechanisms by which environmental triggers lead to this disease phenotype remain poorly understood. In this study, we investigate the impact of representative infectious and pesticide exposures on pSer129 α-Synuclein, with a particular focus on the role of cellular kinases in mediating this process.MethodsNeuronal cells were exposed to two distinct environmental stressors: the pesticide rotenone and the well-characterized gastric bacterium Helicobacter pylori (H. pylori). Phosphorylation of Ser129 α-Synuclein and mitochondrial damage were assessed by immunofluorescence staining or Western blotting. To investigate the involvement of c-Abl, cells were treated with mechanistically distinct c-Abl inhibitors and siRNA. Levels of pSer129 α-Synuclein were quantified by Western blotting, while the activities of the upstream serine/threonine kinase were predicted by kinase profiling and validated by Western blotting. Additionally, transcriptome analyses of treated cells were performed and ingenuity pathway analysis and DESeq2 were applied to identify neurodegenerative pathways affected by the infection/treatment.ResultsThe functional analysis of our RNA-sequencing data revealed that both H. pylori and rotenone induce neuroinflammatory and cellular stress response pathways. Although they likely activate c-Abl through distinct upstream mediators, both triggers ultimately promote α-synuclein phosphorylation. Treatment with the c-Abl inhibitors, Ponatinib and Asciminib, effectively prevented the accumulation of pSer129 α-synuclein and reversed the associated gene expression changes induced by H. pylori or rotenone. Additionally, GSK3β has been identified as a contributor to Ser129 phosphorylation occurring downstream of activated c-Abl signaling. Notably, the vacuolating cytotoxin (VacA) produced by H. pylori appears to play a critical role in c-Abl–mediated phosphorylation of α-synuclein at Ser129.ConclusionsThese findings highlight the pivotal role of c-Abl in α-Synucleinopathies and provide insights into shared mechanisms between infection and pesticide exposure, offering potential therapeutic targets for Parkinson’s disease and related pathologies involving α-Synuclein modification.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12964-025-02399-2.

Pathogen-pathogen interactions represent a critical but little-understood feature of infectious disease dynamics. In particular, experimental evidence suggests that influenza virus and respiratory syncytial virus (RSV) compete with each other, such that infection with one confers temporary protection against the other. However, such interactions are challenging to study using common epidemiologic methods. Here, we use a mathematical modeling approach, in conjunction with detailed surveillance data from Hong Kong and Canada, to infer the strength and duration of the interaction between influenza and RSV. Based on our estimates, we further utilize our model to evaluate the potential conflicting effects of live attenuated influenza vaccines (LAIV) on RSV burden. We find evidence of a moderate to strong, negative, bidirectional interaction, such that infection with either virus yields 40-100% protection against infection with the other for one to five months. Assuming that LAIV reduces RSV susceptibility in a similar manner, we predict that the impact of such a vaccine at the population level would likely depend greatly on underlying viral circulation patterns. More broadly, we highlight the utility of mathematical models as a tool to characterize pathogen-pathogen interactions.

Eosinophils control many aspects of the vertebrate innate immune response. They contribute to homeostasis, inflammatory conditions and defense against pathogens. With the varied functions of eosinophils, they have been found to play both protective and pathogenic roles in many diseases. The zebrafish (Danio rerio) has emerged as a useful model organism for human diseases but tools to study eosinophils in this model are severely limited. Here, we characterize a new and highly specific marker gene, embp, for eosinophils in zebrafish and report a new transgenic reporter line using this gene to visualize eosinophils invivo. In addition, we created an Embp-specific polyclonal Ab that allows the identification of eosinophils ex vivo. These new tools expand the approaches for studying eosinophils in the zebrafish model. Using these reagents, we have been able to identify Embp as a constituent of eosinophil granules in zebrafish. These advances will allow for the investigation of eosinophil biology in the zebrafish model organism, allowing researchers to identify the contribution of eosinophils to the many diseases that are modeled within zebrafish and also shed light on the evolution of eosinophils within vertebrates.