High glucose induces reactivation of latent Kaposi's sarcoma-associated herpesvirus

Fengchun Ye, Yan Zeng, Jingfeng Sha, Tiffany Jones, Kurt Kuhne, Charles Wood, Shou Jiang Gao

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

A high prevalence of Kaposi's sarcoma (KS) is seen in diabetic patients. It is unknown if the physiological conditions of diabetes contribute 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 levels and KSHV replication, we xenografted telomerase-immortalized human umbilical vein endothelial cells that are infected with KSHV (TIVE-KSHV cells) 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 levels induced the production of hydrogen peroxide (H2O2), which downregulated silent information regulator 1 (SIRT1), a class III histone deacetylase (HDAC), resulting in the epigenetic transactivation of KSHV lytic genes. These results suggest that high blood glucose levels in diabetic patients contribute to the development of KS by promoting KSHV lytic replication and infection.

Original languageEnglish (US)
Pages (from-to)9654-9663
Number of pages10
JournalJournal of virology
Volume90
Issue number21
DOIs
StatePublished - Jan 1 2016

Fingerprint

Human herpesvirus 8
Human Herpesvirus 8
Glucose
glucose
Kaposi's Sarcoma
sarcoma
mice
Obese Mice
histone deacetylase
telomerase
Histone Deacetylases
Viral Genes
Telomerase
Human Umbilical Vein Endothelial Cells
cells
transcriptional activation
Epigenomics
Nude Mice
epigenetics
Hydrogen Peroxide

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

High glucose induces reactivation of latent Kaposi's sarcoma-associated herpesvirus. / Ye, Fengchun; Zeng, Yan; Sha, Jingfeng; Jones, Tiffany; Kuhne, Kurt; Wood, Charles; Gao, Shou Jiang.

In: Journal of virology, Vol. 90, No. 21, 01.01.2016, p. 9654-9663.

Research output: Contribution to journalArticle

Ye, Fengchun ; Zeng, Yan ; Sha, Jingfeng ; Jones, Tiffany ; Kuhne, Kurt ; Wood, Charles ; Gao, Shou Jiang. / High glucose induces reactivation of latent Kaposi's sarcoma-associated herpesvirus. In: Journal of virology. 2016 ; Vol. 90, No. 21. pp. 9654-9663.
@article{10b933d471874b24be8a0254a13b3760,
title = "High glucose induces reactivation of latent Kaposi's sarcoma-associated herpesvirus",
abstract = "A high prevalence of Kaposi's sarcoma (KS) is seen in diabetic patients. It is unknown if the physiological conditions of diabetes contribute 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 levels and KSHV replication, we xenografted telomerase-immortalized human umbilical vein endothelial cells that are infected with KSHV (TIVE-KSHV cells) 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 levels induced the production of hydrogen peroxide (H2O2), which downregulated silent information regulator 1 (SIRT1), a class III histone deacetylase (HDAC), resulting in the epigenetic transactivation of KSHV lytic genes. These results suggest that high blood glucose levels in diabetic patients contribute to the development of KS by promoting KSHV lytic replication and infection.",
author = "Fengchun Ye and Yan Zeng and Jingfeng Sha and Tiffany Jones and Kurt Kuhne and Charles Wood and Gao, {Shou Jiang}",
year = "2016",
month = "1",
day = "1",
doi = "10.1128/JVI.01049-16",
language = "English (US)",
volume = "90",
pages = "9654--9663",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "21",

}

TY - JOUR

T1 - High glucose induces reactivation of latent Kaposi's sarcoma-associated herpesvirus

AU - Ye, Fengchun

AU - Zeng, Yan

AU - Sha, Jingfeng

AU - Jones, Tiffany

AU - Kuhne, Kurt

AU - Wood, Charles

AU - Gao, Shou Jiang

PY - 2016/1/1

Y1 - 2016/1/1

N2 - A high prevalence of Kaposi's sarcoma (KS) is seen in diabetic patients. It is unknown if the physiological conditions of diabetes contribute 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 levels and KSHV replication, we xenografted telomerase-immortalized human umbilical vein endothelial cells that are infected with KSHV (TIVE-KSHV cells) 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 levels induced the production of hydrogen peroxide (H2O2), which downregulated silent information regulator 1 (SIRT1), a class III histone deacetylase (HDAC), resulting in the epigenetic transactivation of KSHV lytic genes. These results suggest that high blood glucose levels in diabetic patients contribute to the development of KS by promoting KSHV lytic replication and infection.

AB - A high prevalence of Kaposi's sarcoma (KS) is seen in diabetic patients. It is unknown if the physiological conditions of diabetes contribute 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 levels and KSHV replication, we xenografted telomerase-immortalized human umbilical vein endothelial cells that are infected with KSHV (TIVE-KSHV cells) 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 levels induced the production of hydrogen peroxide (H2O2), which downregulated silent information regulator 1 (SIRT1), a class III histone deacetylase (HDAC), resulting in the epigenetic transactivation of KSHV lytic genes. These results suggest that high blood glucose levels in diabetic patients contribute to the development of KS by promoting KSHV lytic replication and infection.

UR - http://www.scopus.com/inward/record.url?scp=84994000433&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84994000433&partnerID=8YFLogxK

U2 - 10.1128/JVI.01049-16

DO - 10.1128/JVI.01049-16

M3 - Article

VL - 90

SP - 9654

EP - 9663

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 21

ER -