Fluid shear stress delays viral gene expression in a human vascular model.

Viral dissemination through blood vessels is a part of systemic infection and causes endothelial cells to be exposed to viruses. Inside human vasculature, hemodynamic forces exert fluid shear stress (FSS) against blood vessel walls; however, its impact on viral infection remains understudied. To explore the impact of FSS on viral infections, we characterized Vesicular Stomatitis Virus (VSV) and replication-competent, recombinant VSV (rVSV) infections under static and FSS conditions. Infections in either VeroE6 or primary endothelial cells were performed within a microphysiological system (MPS), capable of variable flow rates. We found that when the MPS was seeded with VeroE6 cells both WT VSV and rVSVs were capable of robust infection under static and FSS conditions. In contrast, FSS delayed WT VSV infection and viral spread in primary endothelial cells. Infection with rVSVs increased delays in infection in both cell types, and rVSVs containing an additional gene insertion demonstrated the most attenuation under FSS. These results suggest that FSS can have an important impact on virus infection that is independent of the entry protein used and dependent on genetic modification.