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

Abstract

AbstractKaposi 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.