Protection from HIV-1 infection of primary CD4 T cells by CCR5 silencing is effective for the full spectrum of CCR5 expression.
Stable gene silencing by RNA interference (RNAi) can be achieved by expression of small hairpin RNAs (shRNAs) from RNA polymerase III promoters. We have tested lentiviral vectors expressing shRNAs targetting CCR5 in primary CD4 T cells from donors representing various CCR5 and CCR2 genetic backgrounds covering the full spectrum of CCR5 expression levels and permissiveness for HIV-1 infection. A linear decrease in CCR5 expression resulted in a logarithmic decrease in cellular infection, giving up to three logs protection from HIV-1 infection in vitro. Protection was maintained at very high multiplicity of infection. This and other recent reports on RNAi should open a debate about the use of RNAi gene therapy for HIV infection.
Butticaz
Christophe
C
Infectious Diseases and Institute of Microbiology, Centre Hospitalier Universitaire Vaudois, CHUV, Lausanne, Switzerland.
Ciuffi
Angela
A
Muñoz
Miguel
M
Thomas
Jérôme
J
Bridge
Alan
A
Pebernard
Stephanie
S
Iggo
Richard
R
Meylan
Pascal
P
Telenti
Amalio
A
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D002478:Cells, Cultured; D020868:Gene Silencing; D015316:Genetic Therapy; D005822:Genetic Vectors; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D019713:Receptors, CCR5 / Q000235:genetics* / Q000378:metabolism
D034741:RNA, Small Interfering; D019713:Receptors, CCR5