UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

HIV-1 Lentiviral Vector Immunogenicity Is Mediated by Toll-Like Receptor 3 (TLR3) and TLR7

Breckpot, K; Escors, D; Arce, F; Lopes, L; Karwacz, K; Van Lint, S; Keyaerts, M; (2010) HIV-1 Lentiviral Vector Immunogenicity Is Mediated by Toll-Like Receptor 3 (TLR3) and TLR7. J VIROL , 84 (11) 5627 - 5636. 10.1128/JVI.00014-10.

Full text not available from this repository.

Abstract

Lentiviral vectors are promising vaccine vector candidates that have been tested extensively in preclinical models of infectious disease and cancer immunotherapy. They are also used in gene therapy clinical trials both for the ex vivo modification of cells and for direct in vivo injection. It is therefore critical to understand the mechanism(s) by which such vectors might stimulate the immune system. We evaluated the effect of lentiviral vectors on myeloid dendritic cells (DC), the main target of lentiviral transduction following subcutaneous immunization. The activation of DC cultures was independent of the lentiviral pseudotype but dependent on cell entry and reverse transcription. In vivo-transduced DC also displayed a mature phenotype, produced tumor necrosis factor alpha (TNF-alpha), and stimulated naive CD8(+) T cells. The lentiviral activation of DC was Toll-like receptor (TLR) dependent, as it was inhibited in TRIF/MyD88 knockout (TRIF/MyD88(-/-))DC. TLR3(-/-) or TLR7(-/-) DC were less activated, and reverse transcription was important for the activation of TLR7(-/-) DC. Moreover, lentivirally transduced DC lacking TLR3 or TLR7 had an impaired capacity to induce antigen-specific CD8(+) T-cell responses. In conclusion, we demonstrated TLR-dependent DC activation by lentiviral vectors, explaining their immunogenicity. These data allow the rational development of strategies to manipulate the host's immune response to the transgene.

Type: Article
Title: HIV-1 Lentiviral Vector Immunogenicity Is Mediated by Toll-Like Receptor 3 (TLR3) and TLR7
DOI: 10.1128/JVI.00014-10
Keywords: T-CELL RESPONSES, THERAPEUTIC ANTITUMOR IMMUNITY, PLASMACYTOID DENDRITIC CELLS, IN-VIVO, CANCER-IMMUNOTHERAPY, GENE-TRANSFER, RECOMBINANT LENTIVECTOR, REVERSE-TRANSCRIPTASE, ANTIGEN PRESENTATION, SIGNALING PATHWAY
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: http://discovery.ucl.ac.uk/id/eprint/113082
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item