Abstract SY23-01: KSHV: Immune evasion and oncogenesis

Abstract

Abstract Infection of cells with oncogenic DNA viruses, including herpesviruses, triggers innate immune responses mediated by DNA sensors. Cyclic GMP-AMP synthase (cGAS) is a key DNA sensor that upon activation produces the cyclic dinucleotide cGAMP, which binds and activates Stimulator of Interferon Genes (STING), leading to interferon production and an antiviral response. Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic herpesvirus that is linked to several human malignancies including Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman’s disease (MCD). We have found that KSHV infection activates the cGAS-STING pathway and that cGAS and STING also play an important role in regulating KSHV reactivation from latency. Furthermore, we have identified several KSHV viral proteins that inhibit the cGAS-STING pathway. It appears that modulation of this pathway is important for viral transmission and the lifelong persistence of oncogenic herpesviruses in the human population. Citation Format: Blossom A. Damania. KSHV: Immune evasion and oncogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr SY23-01. doi:10.1158/1538-7445.AM2017-SY23-01