Novel infection of pericytes by Andes virus enhances endothelial cell permeability

Area of Science:

• Virology
• Vascular Biology
• Pathology

Background:

• Andes Virus (ANDV) causes Hantavirus Pulmonary Syndrome (HPS) by infecting pulmonary microvascular endothelial cells (PMECs).
• Pericytes, located basolaterally to PMECs, regulate vascular barrier integrity and immune cell interactions.
• The precise mechanisms by which ANDV disrupts the vascular barrier remain incompletely understood.

Purpose of the Study:

• To investigate the role of pericytes in ANDV infection and subsequent vascular dysfunction.
• To elucidate the contribution of pericyte-mediated effects to Hantavirus Pulmonary Syndrome pathogenesis.

Main Methods:

• Primary human vascular pericytes were infected with ANDV.
• ANDV infection persistence in pericytes was monitored for up to 9 days.
• Supernatants from infected pericytes were used to assess effects on PMEC monolayer permeability.
• Vascular Endothelial Growth Factor (VEGF) levels in supernatants were quantified.

Main Results:

• ANDV persistently infected primary human vascular pericytes for at least 9 days.
• Supernatants from ANDV-infected pericytes significantly increased PMEC monolayer permeability.
• ANDV-infected pericytes secreted high levels of VEGF, a known permeability factor.
• This suggests a mechanism where infected pericytes directly augment vascular permeability.

Conclusions:

• ANDV infection of vascular pericytes is a key factor in promoting vascular barrier dysfunction.
• Pericyte-directed increases in permeability, mediated by VEGF, contribute to Hantavirus Pulmonary Syndrome.
• Targeting ANDV-infected pericytes represents a novel therapeutic strategy for HPS.