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Lentivirus-mediated RNA interference of DC-SIGN expression inhibits human immunodeficiency virus transmission from dendritic cells to T cells.
J Virol. 2004 Oct; 78(20):10848-55.JV

Abstract

In the early events of human immunodeficiency virus type 1 (HIV-1) infection, immature dendritic cells (DCs) expressing the DC-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) receptor capture small amounts of HIV-1 on mucosal surfaces and spread viral infection to CD4(+) T cells in lymph nodes (22, 34, 45). RNA interference has emerged as a powerful tool to gain insight into gene function. For this purpose, lentiviral vectors that express short hairpin RNA (shRNA) for the delivery of small interfering RNA (siRNA) into mammalian cells represent a powerful tool to achieve stable gene silencing. In order to interfere with DC-SIGN function, we developed shRNA-expressing lentiviral vectors capable of conditionally suppressing DC-SIGN expression. Selectivity of inhibition of human DC-SIGN and L-SIGN and chimpanzee and rhesus macaque DC-SIGN was obtained by using distinct siRNAs. Suppression of DC-SIGN expression inhibited the attachment of the gp120 envelope glycoprotein of HIV-1 to DC-SIGN transfectants, as well as transfer of HIV-1 to target cells in trans. Furthermore, shRNA-expressing lentiviral vectors were capable of efficiently suppressing DC-SIGN expression in primary human DCs. DC-SIGN-negative DCs were unable to enhance transfer of HIV-1 infectivity to T cells in trans, demonstrating an essential role for the DC-SIGN receptor in transferring infectious viral particles from DCs to T cells. The present system should have broad applications for studying the function of DC-SIGN in the pathogenesis of HIV as well as other pathogens also recognized by this receptor.

Links

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Authors+Show Affiliations

Arrighi JF
Department of Dermatology and Venereology, University Hospital of Geneva, 4-752, 24 Rue Micheli-du-Crest, 1211 Geneva, Switzerland.
Pion M
No affiliation info available
Wiznerowicz M
No affiliation info available
Geijtenbeek TB
No affiliation info available
Garcia E
No affiliation info available
Abraham S
No affiliation info available
Leuba F
No affiliation info available
Dutoit V
No affiliation info available
Ducrey-Rundquist O
No affiliation info available
van Kooyk Y
No affiliation info available
Trono D
No affiliation info available
Piguet V
No affiliation info available

MeSH

Amino Acid SequenceAnimalsCell Adhesion MoleculesCell LineDendritic CellsGene SilencingHIV Envelope Protein gp120HIV InfectionsHIV-1HeLa CellsHumansLectins, C-TypeLentivirusMacaca mulattaMolecular Sequence DataPan troglodytesRNA InterferenceRNA, MessengerRNA, Small InterferingReceptors, Cell SurfaceT-Lymphocytes

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15452205

Citation

Arrighi, Jean-François, et al. "Lentivirus-mediated RNA Interference of DC-SIGN Expression Inhibits Human Immunodeficiency Virus Transmission From Dendritic Cells to T Cells." Journal of Virology, vol. 78, no. 20, 2004, pp. 10848-55.
Arrighi JF, Pion M, Wiznerowicz M, et al. Lentivirus-mediated RNA interference of DC-SIGN expression inhibits human immunodeficiency virus transmission from dendritic cells to T cells. J Virol. 2004;78(20):10848-55.
Arrighi, J. F., Pion, M., Wiznerowicz, M., Geijtenbeek, T. B., Garcia, E., Abraham, S., Leuba, F., Dutoit, V., Ducrey-Rundquist, O., van Kooyk, Y., Trono, D., & Piguet, V. (2004). Lentivirus-mediated RNA interference of DC-SIGN expression inhibits human immunodeficiency virus transmission from dendritic cells to T cells. Journal of Virology, 78(20), 10848-55.
Arrighi JF, et al. Lentivirus-mediated RNA Interference of DC-SIGN Expression Inhibits Human Immunodeficiency Virus Transmission From Dendritic Cells to T Cells. J Virol. 2004;78(20):10848-55. PubMed PMID: 15452205.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lentivirus-mediated RNA interference of DC-SIGN expression inhibits human immunodeficiency virus transmission from dendritic cells to T cells. AU - Arrighi,Jean-François, AU - Pion,Marjorie, AU - Wiznerowicz,Maciej, AU - Geijtenbeek,Teunis B, AU - Garcia,Eduardo, AU - Abraham,Shahnaz, AU - Leuba,Florence, AU - Dutoit,Valérie, AU - Ducrey-Rundquist,Odile, AU - van Kooyk,Yvette, AU - Trono,Didier, AU - Piguet,Vincent, PY - 2004/9/29/pubmed PY - 2004/11/4/medline PY - 2004/9/29/entrez SP - 10848 EP - 55 JF - Journal of virology JO - J Virol VL - 78 IS - 20 N2 - In the early events of human immunodeficiency virus type 1 (HIV-1) infection, immature dendritic cells (DCs) expressing the DC-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) receptor capture small amounts of HIV-1 on mucosal surfaces and spread viral infection to CD4(+) T cells in lymph nodes (22, 34, 45). RNA interference has emerged as a powerful tool to gain insight into gene function. For this purpose, lentiviral vectors that express short hairpin RNA (shRNA) for the delivery of small interfering RNA (siRNA) into mammalian cells represent a powerful tool to achieve stable gene silencing. In order to interfere with DC-SIGN function, we developed shRNA-expressing lentiviral vectors capable of conditionally suppressing DC-SIGN expression. Selectivity of inhibition of human DC-SIGN and L-SIGN and chimpanzee and rhesus macaque DC-SIGN was obtained by using distinct siRNAs. Suppression of DC-SIGN expression inhibited the attachment of the gp120 envelope glycoprotein of HIV-1 to DC-SIGN transfectants, as well as transfer of HIV-1 to target cells in trans. Furthermore, shRNA-expressing lentiviral vectors were capable of efficiently suppressing DC-SIGN expression in primary human DCs. DC-SIGN-negative DCs were unable to enhance transfer of HIV-1 infectivity to T cells in trans, demonstrating an essential role for the DC-SIGN receptor in transferring infectious viral particles from DCs to T cells. The present system should have broad applications for studying the function of DC-SIGN in the pathogenesis of HIV as well as other pathogens also recognized by this receptor. SN - 0022-538X UR - https://www.unboundmedicine.com/medline/citation/15452205/Lentivirus_mediated_RNA_interference_of_DC_SIGN_expression_inhibits_human_immunodeficiency_virus_transmission_from_dendritic_cells_to_T_cells_ DB - PRIME DP - Unbound Medicine ER -