Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) (also known as human herpesvirus 8) is a gamma-2 herpesvirus believed to be the etiologic agent responsible for KS. In these tumors, KSHV establishes a latent infection in many of the rapidly proliferating and morphologically abnormal cells. The glycine-alanine repeat of the Epstein-Barr virus episome maintenance protein, EBNA-1, limits EBNA-1 epitope presentation to CD8(+) T lymphocytes (CTLs). We have recently described a C-terminal domain in LANA-1 that modulates the interaction with cellular interphase chromatin or elements of the nuclear matrix. Cell cycle analysis indicated that the minichromosome maintenance complex protein, MCM3, bound TR in late-G(1)/S-arrested cells, which coincided with the loss of histone H3 K4 methylation. We also show that RTA can activate the LANA promoter and induce LANA expression in transient reporter assays. In addition to a TATA box at -30 relative to the LT(i) mRNA start sites, we identified three separate RTA response elements that are also utilized by the K14/v-GPCR promoter.
In HHV-7, 52% of healthy adults shed the reactivated HHV-7 in the saliva during the fatigue, and 30% shed HHV-7 after holidays; however, there were no significant differences in their positive ratio and in the amount of viral DNA. Our study describes a novel mechanism through which LANA maintains KSHV latency by targeting a major downstream effector of the Notch signaling pathway.