Blockade of Autocrine CCL5 Responses Inhibits Zika Virus Persistence and Spread in Human Brain Microvascular Endothelial Cells
Megan C. Mladinich, Jonas N. Conde, William R. Schutt, Sook‐Young Sohn, Erich R. Mackow
Abstract
Our findings demonstrate that CCL5 is required for ZIKV to persistently infect human brain ECs that normally protect neuronal compartments. We demonstrate that ZIKV-elicited CCL5 secretion directs autocrine hBMEC activation of ERK1/2 survival pathways via CCR3/CCR5, and inhibiting CCL5/CCR3/CCR5 responses prevented ZIKV persistence and spread. Our findings demonstrate that ZIKV-directed CCL5 secretion promotes hBMEC survival and reveals an underlying mechanism of ZIKV pathogenesis and spread. We demonstrate that antagonists of CCR3/CCR5 inhibit ZIKV persistence in hBMECs and provide potential therapeutic approaches for preventing ZIKV persistence, spread, and neurovirulence.