High Glucose Induces Reactivation of Latent Kaposi’s Sarcoma-Associated Herpesvirus

Authors

Fengchun Ye, Case Western Reserve UniversityFollow
Yan Zeng, University of Nebraska-Lincoln
Jingfeng Sha, Case Western Reserve University
Tiffany Jones, University of Texas Health Sciences Center at San Antonio
Kurt Kuhne, University of Texas Health Sciences Center at San Antonio
Charles Wood, University of Nebraska-LincolnFollow
Shou-Jiang Gao, University of Texas Health Sciences Center at San AntonioFollow

Document Type

Article

Date of this Version

2016

Citation

J. Virol. doi:10.1128/JVI.01049-16

Comments

Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Abstract

High prevalence of Kaposi’s sarcoma (KS) is seen in diabetic patients. It is unknown if the physiological condition of diabetes contributes to KS development. We found elevated levels of viral lytic gene expression when Kaposi’s sarcoma-associated herpesvirus (KSHV) infected cells were cultured in high glucose medium. To demonstrate the association between high glucose and KSHV replication, we xeno29

grafted telomerase-immortalized human umbilical vein endothelial cells that are infected with KSHV (TIVE-KSHV) into hyperglycemic and normal nude mice. The injected cells expressed significantly higher levels of KSHV lytic genes in hyperglycemic mice than in normal mice. We further demonstrated that high glucose induced production of hydrogen peroxide (H2O2), which down regulated silent information regulator 1 (SIRT1), a class-III histone deacetylase (HDAC), resulting in epigenetic transactivation of KSHV lytic genes.These results suggest that high blood glucose in diabetic patients contributes to development of KS by promoting KSHV lytic replication and infection.