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

Abstract

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.

Targeted delivery of miR-34a-5p by phenylborate-coupled polyethylenimide nanocarriers for anti-KSHV treatment

“…After infecting cells, the virus mainly exists in a latent state, and only a limited number of viral genes are expressed in order to evade the immune response of host cells and maintain the survival of the virus ( Li et al, 2018 ; Gam Ze Letova et al, 2021 ; Sharma and Zheng, 2021 ). When it is stimulated by hypoxia, phorbol ester induction, and a variety of inflammatory factors, it will quickly enter the lytic state and produce infectious virus particles, thus infecting neighboring cells ( Long et al, 2021 ; Chinna et al, 2023 ; Davis et al, 2023 ).…”