Abstract
The recombination signal binding protein for immunoglobulin kappa J region (RBPJ) has a dual effect on Kaposi’s sarcoma-associated herpesvirus (KSHV) replication. RBPJ interaction with replication and transcription activator (RTA) is essential for lytic replication, while the interaction with latency-associated nuclear antigen (LANA) facilitates latent infection. Furthermore, our previous study found that LANA decreased RBPJ through upregulating miRNA let-7a. However, it is unclear whether RTA regulates the expression of RBPJ. Here, we show RTA increases RBPJ by decreasing let-7a. During KSHV replication, the RBPJ expression level was positively correlated with the RTA expression level and negatively correlated with the LANA expression level. The let-7a expression level was inverse to RBPJ. Knockdown of RBPJ inhibited the self-activation of RTA promoter and LANA promoter and weakened LANA’s inhibition of RTA promoter. Collectively, these findings indicate that RTA and LANA compete for let-7a/RBPJ signal to control the KSHV replication. Regulating the RBPJ expression level by RTA and LANA plays an important role during KSHV replication.
Highlights
Kaposi’s sarcoma (KS) is the most common neoplasm of untreated acquired immunodeficiency syndrome (AIDS) patients
latency-associated nuclear antigen (LANA) is the key factor in maintaining latent infection, while replication and transcription activator (RTA) is the switch of lytic replication
We want to know whether the expression of let-7a and RBPJ be regulated by RTA
Summary
Kaposi’s sarcoma (KS) is the most common neoplasm of untreated acquired immunodeficiency syndrome (AIDS) patients. According to epidemiological and molecular data, Kaposi’s sarcomaassociated herpesvirus (KSHV) infection is the etiology of KS carcinogenesis. KSHV is linked to two lymphoproliferative disorders, primary effusion lymphoma (Cesarman et al, 1995) and multicentric Castleman’s disease (Soulier et al, 1995). KSHV deploys two alternative genetic programs, latent and lytic in infection, during its infection of endothelial cells and B-lymphocytes (Chang et al, 1994). The circular KSHV episome is retained in the nucleus at a low copy number, and only a handful of viral genes are expressed, and no infectious progeny is produced. Most viral genes are expressed in an ordered cascade during lytic replication
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