Hypoxia and hypoxia-inducible factors in Kaposi sarcoma-associated herpesvirus infection and disease pathogenesis

• Published in: Journal of medical virology Vol. 95; no. 9; p. e29071
• Main Authors: Davis, David A, Shrestha, Prabha, Yarchoan, Robert
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.09.2023
• Subjects: Acquired Immunodeficiency Syndrome; Biology; Cell death; Herpes viruses; Herpesvirus 8, Human - genetics; HIV; Human immunodeficiency virus; Humans; Hypoxia; Immunocompromised Host; Pathogenesis; Sarcoma; Sarcoma, Kaposi; Tumors; Virology; HIF-1; Kaposi sarcoma; hypoxia; HIF-2; gammaherpesvirus; hypoxia response element; viral malignancy
• ISSN: 0146-6615; 1096-9071; 1096-9071
• DOI: 10.1002/jmv.29071

Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi sarcoma and several other tumors and hyperproliferative diseases seen predominantly in human immunodeficiency virus-infected and other immunocompromised persons. There is an increasing body of evidence showing that hypoxia and hypoxia-inducible factors (HIFs) play important roles in the biology of KSHV and in the pathogenesis of KSHV-induced diseases. Hypoxia and HIFs can induce lytic activation of KSHV and KSHV can in turn lead to a hypoxic-like state in infected cells. In this review, we describe the complex interactions between KSHV biology, the cellular responses to hypoxia, and the pathogenesis of KSHV-induced diseases. We also describe how interference with HIFs can lead to decreased tumor growth and/or death of infected cells and KSHV-induced tumors. Finally, we show how these observations may lead to novel strategies for the treatment of KSHV-induced diseases.