Open AccessMultiple Defects, Including Premature Apoptosis, Prevent Kaposi's Sarcoma-Associated Herpesvirus Replication in Murine Cells
Author(s) -
Kathryn Austgen,
Scott A. Oakes,
Don Ganem
Publication year - 2012
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.06600-11
Subject(s) - biology , lytic cycle , virology , viral replication , ectopic expression , virus , kaposi's sarcoma associated herpesvirus , oncolytic virus , virus latency , transcription (linguistics) , dna replication , microbiology and biotechnology , cell culture , dna , herpesviridae , viral disease , genetics , linguistics , philosophy
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.