AUTHOR=Chen Jungang , Song Jiao , James Jennifer , Plaisance-Bonstaff Karlie , Post Steven R. , Qin Zhiqiang , Dai Lu 

TITLE=Activation of IL1 signaling molecules by Kaposi’s sarcoma-associated herpesvirus

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.1049624

DOI=10.3389/fcimb.2022.1049624

ISSN=2235-2988

ABSTRACT=Kaposi’s Sarcoma-associated Herpesvirus (KSHV) is the etiologic agent of several human cancers, including Kaposi’s sarcoma (KS) and Primary effusion lymphoma (PEL), which preferentially arise in immunocompromised patients and lack of effective therapeutic options. Interleukin1 (IL1) family represents a major mediator for inflammation and plays an important role in both innate and adaptive immunity. In contrast to the well-studied IL1 molecules, the activation and functional role of IL1 receptor/co-receptor and other related ligands, such as the IL1 receptor accessory protein (IL1RAP), in KSHV pathogenesis and tumorigenesis remain almost unknown. In the current study, we reported the high activation of multiple IL1 signaling molecules, including IL1, IL36, IL1R1, IL1RAP and IRAKs, during KSHV latent and lytic stages, as well as in clinical samples from patients with KSHV-related malignancies. Directly targeting these molecules especially IL1R1 and IL1RAP significantly impaired the survival and growth of KSHV+ tumor cells, as well as their colony formation on 3-D culture. Taken together, our data indicate the importance of IL1 signaling molecules in KSHV pathogenesis and tumorigenesis, which may represent attractive therapeutic targets against these virus-associated diseases.