Orthoflavivirus omskense NS1 Protein Induces Microvascular Endothelial Permeability In Vitro

Area of Science:

• Virology
• Pathogenesis
• Molecular Biology

Background:

• Omsk hemorrhagic fever virus (OHFV) causes severe zoonotic Omsk hemorrhagic fever (OHF).
• The role of OHFV NS1 protein in pathogenesis is largely unknown.
• NS1 proteins of other flaviviruses are known to affect endothelial permeability.

Purpose of the Study:

• To investigate the role of OHFV NS1 protein in inducing human endothelial cell permeability.
• To understand the molecular mechanisms by which OHFV NS1 affects endothelial cells.

Main Methods:

• Production of recombinant OHFV NS1 protein in eukaryotic cells.
• In vitro treatment of human lung microvascular endothelial cells (HLMVEC) and human umbilical vein endothelial cells (HUVEC) with OHFV NS1.
• RNA sequencing (RNAseq) analysis of treated endothelial cells.

Main Results:

• Recombinant OHFV NS1 directly affects HLMVEC and HUVEC in vitro.
• OHFV NS1 upregulates genes involved in cellular stress, vascular signaling, and cell-cell junction regulation.
• This leads to a general increase in endothelial permeability.

Conclusions:

• OHFV NS1 protein contributes to OHFV pathogenesis by impairing endothelial barrier function.
• Disrupted endothelial barrier and vascular leakage promoted by NS1 may underlie the hemorrhagic manifestations of OHF.