Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A recombinant herpes simplex virus (HSV) capable of inhibiting its own replication as well as the replication of wild-type virus would have greatly increased safety as a general purpose vector for in vivo gene transfer, antitumor therapy, and viral vaccine against HSV infection. By using a tetracycline repressor (tetR)-mediated HSV-1 viral replication switch [Yao and Eriksson (1999). Hum. Gene Ther. 10, 419-427], we have generated a novel anti-HSV-1-specific HSV-1 recombinant (CJ83193) that expresses a trans-dominant negative HSV-1 UL9 origin-binding protein, UL9-C535C. The de novo synthesis of CJ83193 can be suppressed by UL9-C535C by at least 1 x 10(6)-fold in non-tetR-expressing cells, and is subject to tetracycline regulation over a range of four to five orders of magnitude in a tetR-expressing osteosarcoma line. In particular, the UL9-C535C peptides expressed from the CJ83193 genome can inhibit the replication of wild-type HSV-1 by 100- to 200-fold in single-step growth assays. The construction of CJ83193 creates a new general strategy for developing recombinant viral vectors able to function as an intracellular therapy against wild-type viral infections.
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PMID:A novel anti-herpes simplex virus type 1-specific herpes simplex virus type 1 recombinant. 1044 21

The herpes simplex virus (HSV) genome rapidly becomes associated with histones after injection into the host cell nucleus. The viral proteins ICP0 and VP16 are required for efficient viral gene expression and have been implicated in reducing the levels of underacetylated histones on the viral genome, raising the possibility that high levels of underacetylated histones inhibit viral gene expression. The U2OS osteosarcoma cell line is permissive for replication of ICP0 and VP16 mutants and appears to lack an innate antiviral repression mechanism present in other cell types. We therefore used chromatin immunoprecipitation to determine whether U2OS cells are competent to load histones onto HSV DNA and, if so, whether ICP0 and/or VP16 are required to reduce histone occupancy and enhance acetylation in this cell type. High levels of underacetylated histone H3 accumulated at several locations on the viral genome in the absence of VP16 activation function; in contrast, an ICP0 mutant displayed markedly reduced histone levels and enhanced acetylation, similar to wild-type HSV. These results demonstrate that U2OS cells are competent to load underacetylated histones onto HSV DNA and uncover an unexpected role for VP16 in modulating chromatin structure at viral early and late loci. One interpretation of these findings is that ICP0 and VP16 affect viral chromatin structure through separate pathways, and the pathway targeted by ICP0 is defective in U2OS cells. We also show that HSV infection results in decreased histone levels on some actively transcribed genes within the cellular genome, demonstrating that viral infection alters cellular chromatin structure.
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PMID:Herpes simplex virus VP16, but not ICP0, is required to reduce histone occupancy and enhance histone acetylation on viral genomes in U2OS osteosarcoma cells. 1993 31