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

被引:20
作者
Austgen, Kathryn [1 ,2 ,3 ]
Oakes, Scott A. [4 ]
Ganem, Don [1 ,2 ,3 ]
机构
[1] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Microbiol, GW Hooper Fdn, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Dept Med, GW Hooper Fdn, San Francisco, CA USA
[4] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA
关键词
PRIMARY EFFUSION LYMPHOMA; NOTCH SIGNALING PATHWAY; LYTIC SWITCH PROTEIN; GENE-EXPRESSION; CULTURED-CELLS; DNA-SEQUENCES; CYTOCHROME-C; BCL-2; FAMILY; HOST-RANGE; KSHV;
D O I
10.1128/JVI.06600-11
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
引用
收藏
页码:1877 / 1882
页数:6
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