PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 9374034

Viruses and apoptosis.

L S Young·C W Dawson·A G Eliopoulos
View original source ↗Export metadata ↓

Abstract

Virus infection and replication are often associated with apoptosis and this effect is likely to be responsible for much of the pathology associated with infectious disease. Many viruses encode proteins which can inhibit apoptosis thereby either prolonging the survival of infected cells such that the production of progeny virus is maximised or facilitating the establishment of virus persistence. These viral proteins target the cellular pathways responsible for regulating apoptosis and have been instrumental in furthering our understanding of the apoptotic process. Many of the viruses associated with oncogenic transformation have adopted strategies for blocking apoptosis highlighting the centrality of this effect in carcinogenesis. Understanding the mechanisms by which viruses regulate apoptosis may lead to the development of novel therapies for both infectious disease and cancer.

Explore related subjects

Adenovirus E1 ProteinsApoptosisGenes, bcl-2HIV InfectionsHumansReceptors, Tumor Necrosis FactorViral ProteinsVirus DiseasesVirus Physiological PhenomenaJournal ArticleResearch Support, Non-U.S. Gov'tReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

L S Young, C W Dawson, A G Eliopoulos. 1997. Viruses and apoptosis.. https://doi.org/10.1093/oxfordjournals.bmb.a011627

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Rescue of chimeric adenoviral vectors to expand the serotype repertoire.

The successful use of any adenoviral vectors is predicated upon the use of a serotype that is not neutralized by circulating antibodies. However, efforts to develop a diverse repertoire of serologically distinct adenovirus vectors may be hindered by the necessity to generate cell lines to allow for the successful propagation of vectors deleted of essential genes. A strategy to construct chimeric adenoviruses whereby the rescue and propagation of an E1-deleted HAdV-B-derived adenoviral vector can be achieved using existing cell lines such as HEK 293 is reported. It is further shown that this strategy may be more widely applicable.

Adenovirus E1 Proteins↗
PubMed2006

Efficient generation of double heterologous promoter controlled oncolytic adenovirus vectors by a single homologous recombination step in Escherichia coli.

BACKGROUND: Oncolytic adenoviruses are promising agents for the multimodal treatment of cancer. However, tumor-selectivity is crucial for their applicability in patients. Recent studies by several groups demonstrated that oncolytic adenoviruses with tumor-/tissue-specific expression of the E1 and E4 genes, which are pivotal for adenoviral replication, have a specificity profile that is superior to viruses that solely target the expression of E1 or E4 genes. Presently the E1 and E4 regions are modified in a time consuming sequential fashion. RESULTS: Based on the widely used adenoviral cloning system AdEasy we generated a novel transfer vector that allows efficient and rapid generation of conditionally replication-competent adenovirus type 5 based vectors with the viral E1 and E4 genes under the transcriptional control of heterologous promoters. For insertion of the promoters of interest our transfer vector has two unique multiple cloning sites. Additionally, our shuttle plasmid allows encoding of a transgene within the E1A transcription unit. The modifications, including E1 mutations, are introduced into the adenoviral genome by a single homologous recombination step in Escherichia coli. Subsequently infectious viruses are rescued from plasmids. As a proof-of-concept we generated two conditionally replication-competent adenoviruses Ad.Ki x COX and Ad.COX x Ki with the promoters of the Ki-67 protein and the cyclooxygenase-2 (COX-2) driving E1 and E4 and vice versa. CONCLUSION: We demonstrated with our cloning system efficient generation of double heterologous promoter controlled oncolytic adenoviral vectors by a single homologous recombination step in bacteria. The generated viruses showed preferential replication in tumor cells and in a subcutaneous HT-29 colon cancer xenograft model the viruses demonstrated significant oncolytic activity comparable with dl327.

Adenovirus E1 Proteins↗
PubMed2005

Specific and efficient transduction of Cochlear inner hair cells with recombinant adeno-associated virus type 3 vector.

Recombinant adeno-associated virus (AAV) vectors are of interest for cochlear gene therapy because of their ability to mediate the efficient transfer and long-term stable expression of therapeutic genes in a wide variety of postmitotic tissues with minimal vector-related cytotoxicity. In the present study, seven AAV serotypes (AAV1-5, 7, 8) were used to construct vectors. The expression of EGFP by the chicken beta-actin promoter associated with the cytomegalovirus immediate-early enhancer in cochlear cells showed that each of these serotypes successfully targets distinct cochlear cell types. In contrast to the other serotypes, the AAV3 vector specifically transduced cochlear inner hair cells with high efficiency in vivo, while the AAV1, 2, 5, 7, and 8 vectors also transduced these and other cell types, including spiral ganglion and spiral ligament cells. There was no loss of cochlear function with respect to evoked auditory brain-stem responses over the range of frequencies tested after the injection of AAV vectors. These findings are of value for further molecular studies of cochlear inner hair cells and for gene replacement strategies to correct recessive genetic hearing loss due to monogenic mutations in these cells.

Adenovirus E1 Proteins↗