NDLI: Diabetes and risk of Kaposi's sarcoma: effects of high glucose on reactivation and infection of Kaposi's sarcoma-associated herpesvirus

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Diabetes and risk of Kaposi's sarcoma: effects of high glucose on reactivation and infection of Kaposi's sarcoma-associated herpesvirus

Content Provider	Semantic Scholar
Author	Chang, Pey-Jium Yang, Yao-Hsu Chen, Pau-Chung Chen, Lee-Wen Wang, Shie-Shan Shih, Ying-Ju Chen, Li-yu Chen, Chi-Jen Hung, Chien-Hui Lin, Chun-Liang
Copyright Year	2017
Abstract	Patients with diabetes are generally prone to pathogen infection and tumor progression. Here, we investigated the potential association between diabetes and Kaposi's sarcoma (KS), a tumor linked to infection with Kaposi's sarcoma-associated herpesvirus (KSHV). By using Taiwan's National Health Insurance Research Database, we found that diabetes is statistically associated with increased risk of KS in a case-control study. Since a high level of blood sugar is the hallmark of diabetes, we determined whether high glucose promotes both KSHV reactivation and infection, which are crucial for KS pathogenesis. Our results showed that high glucose significantly increases lytic reactivation of KSHV but not Epstein-Barr virus, another related human oncogenic gammaherpesvirus, in latently infected cells. Activation of the transcription factor AP1 by high glucose is critically required for the onset of KSHV lytic reactivation. We also demonstrated that high glucose enhances susceptibility of various target cells to KSHV infection. Particularly, in endothelial and epithelial cells, levels of specific cellular receptors for KSHV entry, including integrin α3β1 and xCT/CD98, are elevated under high glucose conditions, which correlate with the enhanced cell susceptibility to infection. Taken together, our studies implicate that the high-glucose microenvironment may be an important predisposing factor for KS development.
Starting Page	80595
Ending Page	80611
Page Count	17
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://www.oncotarget.com/index.php?journal=oncotarget&op=download&page=article&path%5B%5D=19685&path%5B%5D=62881
PubMed reference number	5655223
Alternate Webpage(s)	https://doi.org/10.18632/oncotarget.19685
DOI	10.18632/oncotarget.19685
Journal	Oncotarget
Volume Number	8
Language	English
Access Restriction	Open
Subject Keyword	Blood Glucose Diabetes Mellitus Epstein-Barr Virus Lysis Murine sarcoma viruses Neoplasms Pathogenic organism Reactivation SARS coronavirus Sugars Tumor Progression gammaherpesvirus human herpesvirus 8
Content Type	Text
Resource Type	Article

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