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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Silencing of HIV-1 subtype C primary isolates by expressed small hairpin RNAs targeted to gag
AIDS Research and Human Retroviruses, Volume 22, No. 5, Year 2006
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Description
Discovery of sequence-specific silencing by activating the RNA interference (RNAi) pathway has led to exciting new strategies for treating infection with human immunodeficiency virus type 1 (HIV-1). Of the HIV-1 subtypes, C is especially common in areas of the world that are worst affected. Although prone to mutation, genome plasticity of this subtype is limited in functionally important regions. We identified conserved sequences within the HIV-1 subtype C gag open reading frame and assessed whether they are suitable targets for inhibition of viral replication by RNA Pol III-driven small hairpin RNAs (shRNAs). Initially, the efficacy of each of a panel of 10 shRNAs against HIV-1 was determined using a reporter assay. shRNAs A and B, which targeted the 5′ end of gag, were most effective and were used to assess inhibition of replication in cultured cells of two R5 isolates (Du151 and Du422) and one X4 virus (SW7). These shRNAs diminished intracellular HIV-1 gag RNA and HIV-1 protein concentrations as well as p24 secretion by up to 80% without inducing an interferon response. However, shRNA-mediated knockdown efficacy against each of these viral isolates varied slightly. These data show successful activation of RNAi to inhibit the replication of biologically distinct HIV-1 subtype C isolates. The effector shRNAs described here are potential candidates for gene therapy applications against the most common global subtype of HIV-1. © Mary Ann Liebert, Inc.
Authors & Co-Authors
Cave, Eleanor M.
South Africa, Johannesburg
University of the Witwatersrand
South Africa, Johannesburg
National Institute for Communicable Diseases
Weinberg, Marc S.
South Africa, Johannesburg
University of the Witwatersrand
Cilliers, Tonie
South Africa, Johannesburg
National Institute for Communicable Diseases
Carmona, Sergio C.
South Africa, Johannesburg
University of the Witwatersrand
Morris, Lynn
South Africa, Johannesburg
National Institute for Communicable Diseases
Arbuthnot, Patrick B.
South Africa, Johannesburg
University of the Witwatersrand
Statistics
Citations: 13
Authors: 6
Affiliations: 2
Identifiers
Doi:
10.1089/aid.2006.22.401
ISSN:
08892229
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases