Work

Multiple Defects, Including Premature Apoptosis, Prevent Kaposi's Sarcoma-Associated Herpesvirus Replication in Murine Cells

Year: 2011

Type: article

Abstract: The development of a mouse model for Kaposi's sarcoma-associated herpesvirus (KSHV) infection has been impeded by the limited host range of the virus. Here, we have examined the molecular basis of this host range restriction. KSHV efficiently enters murine cells and establishes latency. However, ectopic expression of the lytic switch protein RTA (replication and transcription activator) in these cells induces little viral gene expression and no virus production. Upon treatment with histone deacetylase inhibitors, KSHV-infected murine cells display more extensive but aberrant viral transcription and do not support either viral DNA synthesis or the production of infectious virions. These aberrantly infected cells also display markedly enhanced apoptosis. Genetic ablation of the mitochondrial apoptotic pathway in these cells prolongs their survival and permits viral DNA replication but does not rescue the generation of virions. We conclude that multiple defects, both prior to and following DNA synthesis, restrict lytic KSHV infection in murine cells.

Source: Journal of Virology

DOI: 10.1128/jvi.06600-11

Authors: Kathryn Austgen, Scott A. Oakes, Don Ganem

Institutions: Howard Hughes Medical Institute, University of California, San Francisco

Language: English

Topic: Viral-associated cancers and disorders

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Institute of Dental and Craniofacial Research