Astrovirus VA1 infection of mice
Description
Astroviruses commonly cause of gastrointestinal disease in humans and have been linked to fatal cases of encephalitis. A major barrier to the study of human-infecting astroviruses is the lack of an in vivo model, as previous attempts failed to identify a host that supports viral replication. We describe a novel murine model of infection using astrovirus VA1/HMO-C (VA1), an astrovirus with high seroprevalence in humans. VA1 is cardiotropic and viral RNA levels peak in heart tissue seven days post-inoculation in multiple different murine genetic backgrounds. Infectious VA1 particles could be recovered from heart tissue three- and five-days post-inoculation. Intracellular viral capsid was present in heart tissue by immunostaining and viral RNA was detected in cardiac myocytes, endocardium, and endothelial cells based on fluorescent in situ hybridization and confocal microscopy. Histologically, we identified inflammatory infiltrates consistent with myocarditis in some mice, with viral RNA co-localizing with the infiltrates. These foci contained CD3+ T cells and CD68+ macrophages. Viral RNA levels increased by >10-fold in heart tissue or serum samples from Rag1 or Stat1 knockout mice, demonstrating the role of both adaptive and innate immunity in the response to VA1 infection. Based on the in vivo tropisms, we tested cardiac-derived primary cells and determined that VA1 can replicate in primary human cardiac endothelial cells, suggesting a novel cardiovascular tropism in human cells. This novel in vivo model of a human-infecting astrovirus enables further characterization of the host immune response and reveals a new cardiovascular tropism of astroviruses. Experimental data from astrovirus VA1 infection in mice for the manuscript "Novel murine model of human astrovirus infection reveals a cardiovascular tropism: murine model of astrovirus infection". A total of 199 files containing data including mouse weights, tissue weights, qPCR data, focus forming unit measurement, and imaging files are available.
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Steps to reproduce
Data was obtained through mouse experiments. Measurements include mouse weights, qPCR of tissues, measurement of focus forming units, and imaging of tissue using fluorescent in situ hybridization and immunofluorescence. Full methods can be found: https://doi.org/10.1101/2024.10.03.616429.
Institutions
Categories
Funding
National Institute of Allergy and Infectious Diseases
K08AI132745
National Center for Advancing Translational Sciences
UL1TR002345
Children’s Discovery Institute
CDI-FR-2020-906
Additional Metadata for Digital Commons Data@Becker
| Keywords | Virology, Astroviruses, Cardiotropism, Astrovirus VA1, Myocyte, Endothelial Cells, Host-Pathogen Interactions, Tropism |