Cell Cycle Regulatory Functions of the KSHV Oncoprotein LANA

Abstract

Manipulation of cell cycle is a commonly employed strategy of viruses for achieving a favorable cellular environment during infection. Kaposi’s sarcoma-associated herpesvirus (KSHV), the primary etiological agent of several human malignancies including Kaposi’s sarcoma, and primary effusion lymphoma, encodes several oncoproteins that deregulate normal physiology of cell cycle machinery to persist with endothelial cells and B cells and subsequently establish a latent infection. During latency, only a small subset of viral proteins is expressed. Latency-associated nuclear antigen (LANA) is one of the latent antigens shown to be essential for transformation of endothelial cells in vitro. It has been well demonstrated that LANA is critical for the maintenance of latency, episome DNA replication, segregation and gene transcription. In this review, we summarize recent studies and address how LANA functions as an oncoprotein to steer host cell cycle-related events including proliferation and apoptosis by interacting with various cellular and viral factors, and highlight the potential therapeutic strategy of disrupting LANA-dependent signaling as targets in KSHV-associated cancers.

Shugoshin 1 is dislocated by KSHV-encoded LANA inducing aneuploidy

“…LANA is one of a few proteins expressed during KSHV latent infection. LANA regulates multiple pathways by interacting with host proteins through its amino and carboxy terminal domains [ 25 ]. It is also involved in cell cycle regulation with diverse functions.…”

Mechanistic Insights into Chemoresistance Mediated by Oncogenic Viruses in Lymphomas

“…LANA is a master regulator of KSHV latency, and primarily functions to maintain latency, enable episome DNA replication and segregation, and regulates gene transcription. LANA has also been identified as an oncoprotein to steer immune evasion and facilitate tumorigenesis [94,95]. Our recent work highlighted an extended role of LANA in PEL chemoresistance [40,96].…”

Viral-Mediated AURKB Cleavage Promotes Cell Segregation and Tumorigenesis

“…Cell-cycle manipulation is a common evasion strategy that has been adapted by viruses to achieve a favorable cellular environment for replication and infection (Nascimento et al, 2012;Wei et al, 2016). Kaposi's sarcoma-associated herpesvirus (KSHV), also referred to as human herpesvirus 8 (HHV-8), is well recognized as the causative agent of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Cattleman's disease (MCD) (Davis et al, 2015;Gantt and Casper, 2011).…”