Species-specific responses during Seoul orthohantavirus infection in human and rat lung microvascular endothelial cells.

Autor: Noack D; Department of Viroscience, Erasmus University Medical Center, Rotterdam, the Netherlands., van den Hout MCGN; Department of Cell Biology, Erasmus University Medical Center, Rotterdam, the Netherlands.; Center for Biomics, Erasmus University Medical Center, Rotterdam, the Netherlands., Embregts CWE; Department of Viroscience, Erasmus University Medical Center, Rotterdam, the Netherlands., van IJcken WFJ; Department of Cell Biology, Erasmus University Medical Center, Rotterdam, the Netherlands.; Center for Biomics, Erasmus University Medical Center, Rotterdam, the Netherlands., Koopmans MPG; Department of Viroscience, Erasmus University Medical Center, Rotterdam, the Netherlands., Rockx B; Department of Viroscience, Erasmus University Medical Center, Rotterdam, the Netherlands.
Jazyk: angličtina
Zdroj: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2024 Mar 27; Vol. 18 (3), pp. e0012074. Date of Electronic Publication: 2024 Mar 27 (Print Publication: 2024).
DOI: 10.1371/journal.pntd.0012074
Abstrakt: Seoul orthohantavirus (SEOV) is a rat-borne zoonotic virus that is transmitted via inhalation of aerosolized infectious excreta, and can cause hemorrhagic fever with renal syndrome (HFRS) in humans worldwide. In rats, SEOV predominantly exists as a persistent infection in the absence of overt clinical signs. Lack of disease in rats is attributed to downregulation of pro-inflammatory and upregulation of regulatory host responses. As lung microvascular endothelial cells (LMECs) represent a primary target of infection in both human and rats, infections in these cells provide a unique opportunity to study the central role of LMECs in the dichotomy between pathogenicity in both species. In this study, host responses to SEOV infection in primary human and rat LMECs were directly compared on a transcriptional level. As infection of rat LMECs was more efficient than human LMECs, the majority of anti-viral defense responses were observed earlier in rat LMECs. Most prominently, SEOV-induced processes in both species included responses to cytokine stimulus, negative regulation of innate immune responses, responses to type I and II interferons, regulation of pattern recognition receptor signaling and MHC-I signaling. However, over time, in the rat LMECs, responses shifted from an anti-viral state towards a more immunotolerant state displayed by a PD-L1, B2M-, JAK2-focused interaction network aiding in negative regulation of cytotoxic CD8-positive T cell activation. This suggests a novel mechanism by which species-specific orthohantavirus-induced endothelium and T cell crosstalk may play a crucial role in the development of acute disease in humans and persistence in rodents.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Noack et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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