Abstract
Kaposi’s sarcoma-associated herpesvirus (KSHV) belongs to the gamma herpesvirus family and is the causative agent of various lymphoproliferative diseases in humans. KSHV, like other herpesviruses, establishes life-long latent infection with the expression of a limited number of viral genes. Expression of these genes is tightly regulated by both the viral and cellular factors. Recent advancements in identifying the expression profiles of viral transcripts, using tilling arrays and next generation sequencing have identified additional coding and non-coding transcripts in the KSHV genome. Determining the functions of these transcripts will provide a better understanding of the mechanisms utilized by KSHV in altering cellular pathways involved in promoting cell growth and tumorigenesis. Replication of the viral genome is critical in maintaining the existing copies of the viral episomes during both latent and lytic phases of the viral life cycle. The replication of the viral episome is facilitated by viral components responsible for recruiting chromatin modifying enzymes and replication factors for altering the chromatin complexity and replication initiation functions, respectively. Importantly, chromatin modification of the viral genome plays a crucial role in determining whether the viral genome will persist as latent episome or undergo lytic reactivation. Additionally, chromatinization of the incoming virion DNA, which lacks chromatin structure, in the target cells during primary infection, helps in establishing latent infection. Here, we discuss the recent advancements on our understating of KSHV genome chromatinization and the consequences of chromatin modifications on viral life cycle.
Highlights
Kaposi’s Sarcoma (KS), first described in 1872 by the Hungarian dermatologist Moritz Kaposi, is defined as a multiple idiopathic sarcoma of the skin
Chromatin and epigenetic modulation of Kaposi’s sarcoma-associated herpesvirus (KSHV) genome represents a novel antiviral target for blocking virus-mediated tumorigenesis. This compilation review summarizes some of the emerging concepts that will describe in the detail our current knowledge of chromatin assembly and remodeling factors, and epigenetic alterations, including DNA methylation, post-translational histone modifications, and nucleosome occupancy of KSHV genome, as the master controllers of KSHV’s biphasic life cycle, gene expression pattern and associated pathogenesis
The results indicated a heterogeneous chromatin structure with both fully closed and open conformations being present at investigated promoter regions in the KSHV genome
Summary
Kaposi’s Sarcoma (KS), first described in 1872 by the Hungarian dermatologist Moritz Kaposi, is defined as a multiple idiopathic sarcoma of the skin. The causative agent of Kaposi’s sarcoma was identified as the human herpesvirus 8 (HHV8), or Kaposi’s sarcoma-associated herpesvirus (KSHV). Since its initial discovery in KS lesions, KSHV has been tightly linked with endothelial tumors, Kaposi’s sarcoma and two B-cell lymphoproliferative disorders, primary effusion lymphoma (PEL), known as body cavity-based lymphoma [2], and a plasmablastic variant of multicentric Castleman’s disease (MCD) [3]. KSHV has been linked to different lymphomas, including Burkitt’s lymphoma, Germinotropic Lymphoproliferative Disorder (GLD), multiple myeloma, angio-sarcomas, malignant skin tumors, angio-immunoblastic lymphoma and primary pulmonary hypertension [4,5,6]. There have been reports of a new KSHV/HHV8-associated germinotropic lymphoproliferative disorder in HIV-seronegative individuals [7]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
