Kaposi's sarcoma-associated herpesvirus replication and transcription activator protein activates CD274/PD-L1 gene promoter.
Cancer Sci
; 114(4): 1718-1728, 2023 Apr.
Article
em En
| MEDLINE
| ID: mdl-36411531
ABSTRACT
Kaposi's sarcoma-associated herpesvirus (KSHV) is responsible for the pathogenesis of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease. The expression of immunosuppressive genes, such as IL-10 and CD274/PD-L1 is observed during KSHV-associated pathogenesis, and the modulation of the host immune system by KSHV contributes to establishing viral persistence in the host. Understanding the mechanism that allows the virus to evade host cell immunity would be helpful in order to develop therapeutic strategies for KSHV malignancy. In this study, we show that KSHV replication and transcriptional activator (K-RTA), an essential activator of the viral lytic cycle, transactivates the CD274/PD-L1 gene promoter. Mechanistically, we demonstrate that the binding of K-RTA to the cellular specificity protein 1 (SP1) is critical for K-RTA-mediated CD274/PD-L1 promoter activation. These findings suggest that K-RTA cooperates with intracellular SP1 to activate the expression of CD274/PD-L1, which helps the virus regulate immune checkpoints to escape and survive.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Imediatamente Precoces
/
Herpesvirus Humano 8
Tipo de estudo:
Clinical_trials
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Cancer Sci
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Japão