Inhibition of human immunodeficiency virus type 1 replication in primary macrophages by using Tat- or CCR5-specific small interfering RNAs expressed from a lentivirus vector.

Published

Journal Article

Although several groups have demonstrated that RNA interference, induced by transfection of small interfering RNA (siRNA) duplexes, can protect cells against a viral challenge in culture, this protection is transient. Here, we describe lentivirus expression vectors that can stably express siRNAs at levels sufficient to block virus replication. We have used these vectors to stably express siRNAs specific for the essential human immunodeficiency virus type 1 (HIV-1) Tat transcription factor or specific for a cellular coreceptor, CCR5, that is required for infection by the majority of primary HIV-1 isolates. These lentivirus vectors are shown to protect cells, including primary macrophages, against HIV-1 infection in culture by inducing selective degradation of their target mRNA species. These data suggest that it should be possible to block the expression of specific viral or cellular genes in vivo by using viral vectors to stably express the appropriate siRNAs.

Full Text

Duke Authors

Cited Authors

  • Lee, M-TM; Coburn, GA; McClure, MO; Cullen, BR

Published Date

  • November 2003

Published In

Volume / Issue

  • 77 / 22

Start / End Page

  • 11964 - 11972

PubMed ID

  • 14581533

Pubmed Central ID

  • 14581533

Electronic International Standard Serial Number (EISSN)

  • 1098-5514

International Standard Serial Number (ISSN)

  • 0022-538X

Digital Object Identifier (DOI)

  • 10.1128/JVI.77.22.11964-11972.2003

Language

  • eng