Regulation of KSHV replication by glycoprotein B: chronicles of a virus and its host

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Ossie F. Dyson (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Advisor

Shaw Akula

Abstract: Kaposi's sarcoma-associated herpesvirus (KSHV) the causative agent of three cancers: Kaposi's sarcoma (KS) primary effusion lymphoma (PEL) and the plasmablastic form of multicentric Castleman disease (MCD) shares many characteristics with other herpesviruses including the unique ability to maneuver between latent and lytic modes of infection. During a latent stage of infection viruses remain dormant with very few genes being expressed. Alternatively lytic infection is distinguished by the production of infectious virions and virus dissemination. In KSHV pathogenesis the majority of infected cells support latent infections while less than 3% of them support spontaneous lytic replication. Regulation of latent and lytic infections involves interactions between virus-encoded and cellular factors. However the exact mechanism(s) supporting it is poorly understood. In the following study we provide evidence supporting the role for KSHV-encoded glycoprotein B (gB) a structural protein to inhibit KSHV reactivation from latency via altering the expression of the cellular transcription factor Early growth response-1 (Egr-1). We observed Egr-1 to specifically bind to two separate locations on the KSHV-encoded ORF50 promoter which plays a significant role in KSHV reactivation. Furthermore we provide evidence supporting the potential mechanism for KSHV gB to regulate KSHV reactivation. These studies provide new insights and appreciation for the role of virus-encoded structural proteins to support virus latency and may contribute to the development of future therapies. 

Additional Information

Publication

Dissertation

Date: 2011

Keywords

Microbiology, Molecular biology, Egr-1, gB, KSHV, Reactivation

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