Melero, I. | bioRxiv Science

bioRxiv2022

Host age-dependent evolution of a plant RNA virus

Viruses are obligate pathogens that entirely rely on their host resources to complete their infectious cycle. The availability of such resources depends upon external and internal factors, being host age one of the most relevant ones. The interplay between host age and virus evolution has not been thoroughly studied in plants. Here, we have used the Arabidopsis thaliana - turnip mosaic virus (TuMV) pathosystem to study plant-virus interactions and virus evolution at three different host ages: vegetative (juvenile), bolting (transition) and reproductive (mature) stages. After infecting plants with a naive and a well-adapted TuMV isolates, we observed that the older the host the faster and more severe the infections were. The same trend was observed for several other viruses. Thereafter, we experimentally evolved lineages of the naive and the well-adapted TuMV isolates in plants from each of the three developmental stages. All evolved viruses enhanced their infection phenotypes, being this increase more intense on viruses evolved in younger hosts. The genomic changes of the evolved viral lineages revealed mutation patterns that strongly depended on the founder viral isolate as well as on the age of the host wherein the lineages evolved.

evolutionary biology↗

bioRxiv2021

Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune pathways related to tissue injury

Severe lung damage in COVID-19 involves complex interactions between diverse populations of immune and stromal cells. In this study, we used a spatial transcriptomics approach to delineate the cells, pathways and genes present across the spectrum of histopathological damage in COVID-19 lung tissue. We applied correlation network-based approaches to deconvolve gene expression data from areas of interest within well preserved post-mortem lung samples from three patients. Despite substantial inter-patient heterogeneity we discovered evidence for a common immune cell signaling circuit in areas of severe tissue that involves crosstalk between cytotoxic lymphocytes and pro-inflammatory macrophages. Expression of IFNG by cytotoxic lymphocytes was associated with induction of chemokines including CXCL9, CXCL10 and CXCL11 which are known to promote the recruitment of CXCR3+ immune cells. The tumour necrosis factor (TNF) superfamily members BAFF (TNFSF13B) and TRAIL (TNFSF10) were found to be consistently upregulated in the areas with severe tissue damage. We used published spatial and single cell SARS-CoV-2 datasets to confirm our findings in the lung tissue from additional cohorts of COVID-19 patients. The resulting model of severe COVID-19 immune-mediated tissue pathology may inform future therapeutic strategies. One Sentence SummarySpatial analysis identifies IFN{gamma} response signatures as focal to severe alveolar damage in COVID-19 pneumonitis.

immunology↗