Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling by array of mouse FV env-specific CD4 TCRbeta transgenic cells primed by an Ad5 vector

ABSTRACT: Comparison of the transcriptional profiles of FV env-specific CD4 TCRbeta transgenic cells primed by an Ad5 vector with those primed by FV and submitted in E-MEXP-2950

ORGANISM(S): Mus musculus

SUBMITTER: George Kassiotis

PROVIDER: E-MTAB-2210 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Clonotypic composition of the CD4+ T cell response to a vectored retroviral antigen is determined by its speed.

Thorborn Georgina G Ploquin Mickaël J MJ Eksmond Urszula U Pike Rebecca R Bayer Wibke W Dittmer Ulf U Hasenkrug Kim J KJ Pepper Marion M Kassiotis George G

Journal of immunology (Baltimore, Md. : 1950) 20140707 4

The mechanisms whereby different vaccines may expand distinct Ag-specific T cell clonotypes or induce disparate degrees of protection are incompletely understood. We found that several delivery modes of a model retroviral Ag, including natural infection, preferentially expanded initially rare high-avidity CD4(+) T cell clonotypes, known to mediate protection. In contrast, the same Ag vectored by human adenovirus serotype 5 induced clonotypic expansion irrespective of avidity, eliciting a predomi ...[more]

PMID: 25000983

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Project description:Replicating viruses have broad applications in biomedicine, notably in cancer virotherapy and in the design of attenuated vaccines, however uncontrolled virus replication in vulnerable tissues can give pathology and often restricts the use of potent strains. Increased knowledge of tissue-selective microRNA expression now affords the possibility of engineering replicating viruses that are attenuated at the RNA level in sites of potential pathology, but retain wild type replication activity at sites not expressing the relevant microRNA. To assess the usefulness of this approach for the DNA virus, adenovirus, we have engineered a hepatocyte-safe wild type adenovirus 5 (Ad5), which normally mediates significant toxicity and is potentially lethal in mice. To do this we have included binding sites for hepatocyte-selective microRNA122a within the 3' UTR of the E1A transcription cassette. Imaging versions of these viruses, produced by fusing E1A with luciferase, showed that inclusion of microRNA122a binding sites caused up to 80 fold decreased hepatic expression of E1A following intravenous delivery to mice. Animals administered a ten-times lethal dose of wild type Ad5 (5 x 1010 viral particles/mouse) showed substantial hepatic genome replication and extensive liver pathology, while inclusion of 4 microRNA binding sites decreased replication 50-fold and virtually abrogated liver toxicity. This modified wild type virus retained full activity within cancer cells and provides a potent, liver-safe oncolytic virus. In addition to providing many potent new viruses for cancer virotherapy, microRNA-control of virus replication should provide a new strategy for designing safe attenuated vaccines applied across a broad range of viral diseases. four groups which we had were: WT: RNA extracted from livers of mice treated with wild type Ad5, 3 Replicates miR: RNA extracted from livers of mice treated with wild type Ad5 bearing mir122-binding sites in the 3'UTR of E1A (3 Replicates) Luc: RNA extracted from livers of mice treated with non-replicating Ad5 (3 Replicates) PBS: RNA extracted from livers of mice treated with PBS only (3 Replicates)

Dataset Information

Transcription profiling by array of mouse FV env-specific CD4 TCRbeta transgenic cells primed by an Ad5 vector

Publications

Clonotypic composition of the CD4+ T cell response to a vectored retroviral antigen is determined by its speed.

Similar Datasets

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