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. IMPORTANCE Multiple epidemiological studies have reported a higher prevalence of classic KS in diabetic patients. By using both in vitro and in vivo models, we demonstrated an association between high glucose levels and KSHV lytic replication. High glucose levels induce oxidative stress and the production of H2O2, which mediates the reactivation of latent KSHV through multiple mechanisms. Our results provide the first experimental evidence and mechanistic support for the association of classic KS with diabetes.

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

Long-term combined rIFN-alpha-2a and zidovudine therapy for HIV-associated Kaposi's sarcoma: clinical consequences and side effects.

Thoracic manifestations of the acquired immune deficiency syndrome.

Among 350 recipients of renal transplants seen at the Riyadh Military Hospital, 12 developed Kaposi's sarcoma. Two of these sarcomas presented primarily as a problem of diffuse lung infiltrates in an immunocompromised host. In one the diagnosis was established by transbronchial lung biopsy. Withdrawal of immunosuppression led to satisfactory radiological resolution in both patients.

https://thorax.bmj.com/content/thoraxjnl/43/8/653.full.pdf

Pulmonary Kaposi's sarcoma in two recipients of renal transplants.

immunosuppression.In view of these findings immunosuppressive treatmentwasstopped. Hedevelopedafeverandbecameincreasinglyshort ofbreath, which was not relieved by the removal of1-2 1 offluid fromthechest. Hisarterial blood gas tensionsdeteriorated (Pao2 66 mmHg (8-8 kPa) while he wasbreathingair).Aright thoracotomyandlungbiopsywerecarried outinMay1986to makesurethat thetransbronchial lungbiopsyhad not missed an

David Grieder

Papers

Asthma, Kaposi's Sarcoma, and Nodular Pulmonary Infiltrates