siRNA-directed inhibition of HIV-1 infection.
RNA interference silences gene expression through short interfering 21 23-mer double-strand RNA segments that guide mRNA degradation in a sequence-specific fashion. Here we report that siRNAs inhibit virus production by targeting the mRNAs for either the HIV-1 cellular receptor CD4, the viral structural Gag protein or green fluorescence protein substituted for the Nef regulatory protein. siRNAs effectively inhibit pre- and/or post-integration infection events in the HIV-1 life cycle. Thus, siRNAs may have potential for therapeutic intervention in HIV-1 and other viral infections.
Novina
Carl D
CD
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Murray
Michael F
MF
Dykxhoorn
Derek M
DM
Beresford
Paul J
PJ
Riess
Jonathan
J
Lee
Sang-Kyung
SK
Collman
Ronald G
RG
Lieberman
Judy
J
Shankar
Premlata
P
Sharp
Phillip A
PA
D001483:Base Sequence; D015704:CD4 Antigens / Q000502:physiology; D002460:Cell Line; D020868:Gene Silencing; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D016372:RNA, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering; D022661:RNA, Untranslated / Q000494:pharmacology / Q000502:physiology*; D019713:Receptors, CCR5 / Q000502:physiology; D014162:Transfection; D016662:Virus Integration / Q000187:drug effects
D015704:CD4 Antigens; D016372:RNA, Antisense; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D022661:RNA, Untranslated; D019713:Receptors, CCR5