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Formation and disruption of TRIM19 containing nuclear bodies in neurons during herpes simplex virus in vivo
Author(s) -
Sawtell Nancy M,
Thompson Richard L
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.672.41
Subject(s) - biology , viral replication , herpes simplex virus , in vivo , promyelocytic leukemia protein , virology , sumo protein , downregulation and upregulation , virus , microbiology and biotechnology , cell culture , genetics , gene , acute promyelocytic leukemia , retinoic acid , ubiquitin
The tripartite motif (TRIM) family is emerging as a novel class of antiviral proteins involved in innate host defense. TRIM19 (promyelocytic leukemia protein, PML) orchestrates the formation of ND10 which are distinct intranuclear substructures. The hypothesis that these bodies are part of the cellular antiviral response arose from the observation that herpes viruses as well as other viruses actively disrupt these bodies. Maul and Everett have demonstrated that the HSV IE protein, ICP0 is necessary and sufficient for disruption of ND10 in cell culture. Whether ND10 form and/or are disrupted in the context of a herpes viral infection in vivo is not known. In this study we have utilized wild type and PML‐/‐ mice and parental and ICP0 null mutant viruses to examine the role of ND10 formation and disruption during HSV infection in vivo. Viral replication, establishment of latency, and viral reactivation in vivo were compared in the presence and absence of ICP0 and in the presence and absence of PML. HSV infection resulted in the global upregulation of ND10 within cells of infected tissues which was not restricted to those cells that were infected. In the absence of ICP0 function, ND10 were not disrupted in infected neurons. These neurons underwent apoptosis prior to infectious virus production. Thus ND10 are broadly upregulated by viral infection in vivo and their disruption is correlated with productive viral replication. NIH RO1AI32121