The Role of ORF59 and PAN ENE in Viral Replication of KSHV
type: CreativeWork
description: Kaposi's sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA virus and the etiological agent for a number of oncogenic diseases including Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion lymphoma (PEL). Similarly to other herpesviruses, KSHV can establish life-long infections. After a primary infection, the virus remains within the host as a persistent infection with periodic episodes of reactivation due to a variety of factors including environmental stimuli or waning immunity. Particularly, in immune-compromised individuals, reactivation can result in the production of new infectious virions which can in turn drive the progression of KSHV-associated malignancies. During reactivation, multiple viral and cellular factors are required to ensure progression through the KSHV viral lytic cycle. One of these factors is the viral polymerase processivity factor ORF59. The main functions of ORF59 are to localize the viral polymerase to the nucleus and to aid in polymerase processivity during viral DNA synthesis. Recently, ORF59 has been described to be a multifunctional protein. These functions extend beyond direct involvement in viral DNA synthesis to include regulation of viral gene transcription and modulation of the cellular environment to facilitate viral replication. Among the identified ORF59 binding partners are histones. Our work identified the domains of ORF59 that are required for interaction with histones and also determined that the carboxy-terminus is not required for viral replication. However, while we ascertained the domains required for ORF59 to interact with histones and found that these are also required for viral replication, the functional role for ORF59 and histone interaction remains to be determined. ORF59 is known to interact with a highly abundant viral long non-coding RNA (lnc RNA), polyadenylated nuclear (PAN) RNA. Previous work has suggested that PAN plays a crucial role during replication and also …
abstract: Kaposi's sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA virus and the etiological agent for a number of oncogenic diseases including Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion lymphoma (PEL). Similarly to other herpesviruses, KSHV can establish life-long infections. After a primary infection, the virus remains within the host as a persistent infection with periodic episodes of reactivation due to a variety of factors including environmental stimuli or waning immunity. Particularly, in immune-compromised individuals, reactivation can result in the production of new infectious virions which can in turn drive the progression of KSHV-associated malignancies. During reactivation, multiple viral and cellular factors are required to ensure progression through the KSHV viral lytic cycle. One of these factors is the viral polymerase processivity factor ORF59. The main functions of ORF59 are to localize the viral polymerase to the nucleus and to aid in polymerase processivity during viral DNA synthesis. Recently, ORF59 has been described to be a multifunctional protein. These functions extend beyond direct involvement in viral DNA synthesis to include regulation of viral gene transcription and modulation of the cellular environment to facilitate viral replication. Among the identified ORF59 binding partners are histones. Our work identified the domains of ORF59 that are required for interaction with histones and also determined that the carboxy-terminus is not required for viral replication. However, while we ascertained the domains required for ORF59 to interact with histones and found that these are also required for viral replication, the functional role for ORF59 and histone interaction remains to be determined. ORF59 is known to interact with a highly abundant viral long non-coding RNA (lnc RNA), polyadenylated nuclear (PAN) RNA. Previous work has suggested that PAN plays a crucial role during replication and also …
author: Gutierrez, Isaura Vanessa
keywords: ENE, KSHV, long non-coding RNA, ORF59, PAN, Processivity Factor
date published: 2021
date modified: 2026-07-27T21:47:03Z
provider: University of Nevada - Reno
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Nevada - Reno

PropertyValue
property ID: Handle
value: http://hdl.handle.net/11714/7926