Angiopoietin-1/Tie2 Activation as a Therapeutic Hypothesis for Hantavirus-Induced Vascular Permeability

Abstract

Severe hantavirus infection produces extensive vascular leakage, driven by a combination of endothelial dysfunction, dysregulated inflammation, VEGF-mediated hyperpermeability, angiopoietin imbalance, and degradation of the endothelial glycocalyx. This narrative review draws on the peer-reviewed literature, with particular attention to work published between 2016 and 2026, to examine how hantavirus-induced vascular permeability arises in hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), and how Angiopoietin-1 (Ang-1)/Tie2 signaling and glycocalyx injury contribute to endothelial barrier failure. Direct hantavirus evidence shows that Ang-1 inhibits hantavirus-directed endothelial permeability in vitro and that angiopoietin dysregulation tracks with disease severity in patients; findings that Tie2 activation curbs vascular leakage in sepsis and other non-hantavirus models are mechanistically suggestive but remain inferential rather than hantavirus-specific. No hantavirus animal model or clinical trial has yet evaluated Ang-1/Tie2-directed therapy, so this review treats the approach as a testable hypothesis rather than an established or recommended treatment; confirming its therapeutic value will require dedicated hantavirus-specific animal and clinical studies.

Keywords

hantavirus, endothelial dysfunction, vascular permeability, angiopoietin, Tie2, therapeutic hypothesis

Citation

Publication Details

ISSN: Online ISSN: 3143-5653

License: Author-retained; open access display by NSRI unless a separate article license states otherwise.

Peer review status: NSRI uses editorial and scholarly review. When appropriate, manuscripts may undergo blinded review by reviewers with relevant subject knowledge.

AI disclosure: No AI disclosure is attached to this public record unless stated in the manuscript.

Conflict of interest statement: No conflict of interest statement is attached to this public record unless stated in the manuscript.

References

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