Novel infection of pericytes by Andes virus enhances endothelial cell permeability

•ANDV causes a severe capillary leak syndrome hantavirus pulmonary syndrome.•Endothelial cells (EC) and pericytes regulate pulmonary capillary permeability.•We discovered that ANDV persistently infects primary human vascular pericytes.•ANDV infected pericytes direct VEGF secretion and cause EC permeability.•We reveal a novel pericyte directed mechanism of ANDV induced pulmonary edema. Andes Virus (ANDV) non-lytically infects pulmonary microvascular endothelial cells (PMECs) causing a severe capillary leak syndrome termed Hantavirus Pulmonary Syndrome (HPS). Basolaterally, PMECs are in contact with pericytes which play critical roles in regulating PMEC permeability and immune cell recruitment. We discovered that ANDV persistently infects primary human vascular pericytes for up to 9 days, and that PMEC monolayer permeability was increased by supernatants from ANDV-infected pericytes. Pericyte-directed PMEC permeability was consistent with the high-level secretion of the permeability factor VEGF (vascular endothelial growth factor) elicited by ANDV-infected pericytes. These findings suggest that ANDV infection of pericytes augments PMEC permeability and reveal a novel mechanism of pericyte-directed vascular barrier dysfunction that contributes to HPS and provides new therapeutic targets.