Zoster-Associated Prothrombotic Plasma Exosomes and Increased Stroke Risk

Authors

Andrew N Bubak
Christina Coughlan
Janelle Posey
Anthony J Saviola
Christy S Niemeyer
Serena W R Lewis
Sara Bustos Lopez
Adriana Solano
Stephen K Tyring
Cassidy Delaney
Keith B Neeves
Ravi Mahalingam
Kirk C Hansen
Maria A Nagel

Publication Date

4-18-2023

Journal

The Journal of Infectious Diseases

Abstract

Herpes zoster (HZ; shingles) caused by varicella zoster virus reactivation increases stroke risk for up to 1 year after HZ. The underlying mechanisms are unclear, however, the development of stroke distant from the site of zoster (eg, thoracic, lumbar, sacral) that can occur months after resolution of rash points to a long-lasting, virus-induced soluble factor (or factors) that can trigger thrombosis and/or vasculitis. Herein, we investigated the content and contributions of circulating plasma exosomes from HZ and non-HZ patient samples. Compared with non-HZ exosomes, HZ exosomes (1) contained proteins conferring a prothrombotic state to recipient cells and (2) activated platelets leading to the formation of platelet-leukocyte aggregates. Exosomes 3 months after HZ yielded similar results and also triggered cerebrovascular cells to secrete the proinflammatory cytokines, interleukin 6 and 8. These results can potentially change clinical practice through addition of antiplatelet agents for HZ and initiatives to increase HZ vaccine uptake to decrease stroke risk.

Keywords

Humans, Exosomes, Herpes Zoster, Herpesvirus 3, Human, Stroke, Risk Assessment, Male, Female, Plasma, Thrombosis