HHV8 [LN53]

Human herpesvirus-8//Kaposi’s sarcoma-associated herpesvirus (HHV-8/KSHV) and macaque retroperitoneal fibromatosis herpesvirus (RFHV) were originally identified in in AIDS patients in association with Kaposi’s sarcoma (KS) and in retroperitoneal fibromatosis (RF) tumor lesions of macaques with simian AIDS, respectively. The most prominent protein expressed in cells latently infected with KSHV and RFHV is the orf73 gene product known as the latency-associated nuclear antigen (LANA or LNA). LANA is a nuclear protein that functions to ensure the maintenance of the viral genome by tethering the viral episomal DNA to host cell chromosomes. LANA also regulates the cellular transcription program in host cells through interaction with a number of cellular proteins, including transcriptional regulators and known tumor suppressors, p53 and pRB. In addtion, LANA directly influences the viral transcription program and helps maintain the latent state of the virus by inhibiting viral replication. KSHV LANA consists of a serine- and proline-rich N-terminal domain with a nuclear localization signal (NLS), a chromatin-binding motif (CBM), and domains responsible for interaction with the transcription regulators, mSin3 complex and Sp1. The central domain contains several highly repetitive acidic regions that vary in length and are responsible for the size variation of LANA proteins from different KSHV isolates that can range from 1003 to 1162 amino acids. The proline-rich C-terminal third domain contains another NLS and is responsible for LANA dimerization and binding to the terminal repeats (TR) of the viral genomic DNA. The C-terminal domain is responsible for interaction with tumor suppressors pRB and p53.