Articles of Significant Interest in This Issue

Abstract

Andes virus (ANDV) selectively infects pulmonary microvascular endothelial cells (PMECs), causing a 35% fatal acute pulmonary edema termed hantavirus pulmonary syndrome (HPS). However, the mechanism of ANDV-induced vascular permeability remains an enigma. Gorbunova and Mackow (e00396-21) found that the ANDV N-protein binds to RhoGDI, the primary repressor of RhoA-directed vascular permeability. N-protein binding to S34-phosphorylated RhoGDI inhibited RhoGDI binding and repression of RhoA, revealing a novel edemagenic mechanism that permits ANDV to cause HPS. These findings rationalize targeting PKCα phosphorylation of RhoGDI to therapeutically inhibit HPS patient edema and may be broadly applicable to other causes of acute respiratory distress.