Double-stranded nef RNA interferes with human immunodeficiency virus type 1 replication.
RNA interference (RNAi) has been reported to be post-transcriptional gene silencing (PTGS) by approximately 500 nucleotide-(nt)-long double-stranded (ds) RNA that specifically targets homologous sequences of messenger RNA. In this report, we describe inhibition of HIV-1 transcription by synthetic dsRNAs constructed with mutated nef genes (nef dsRNAs) derived from long-term non-progressors (LTNPs) using cotransfection of the target gene-expressing plasmid and dsRNA. The effects of nef dsRNAs were examined with luciferase (Luc) reporter which is combined with the HIV-1 (SF2) LTR in persistently HIV-1-infected T cell and macrophage cell lines. At 48 hr, a defective nef dsRNA (556 nt) suppressed Luc activity more potently than did SF2 full-length nef dsRNA (744 nt), suggesting that approximately 500 nt-long nef dsRNA could interfere with the HIV-1 transcription.
Yamamoto
Takuya
T
Division of Nutritional Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Aichi 467-8603, Japan.
Omoto
Shinya
S
Mizuguchi
Masaaki
M
Mizukami
Hajime
H
Okuyama
Harumi
H
Okada
Noriko
N
Saksena
Nitin K
NK
Brisibe
Ebiamadon A
EA
Otake
Kaori
K
Fuji
Yoichi R
YR
D015693:Gene Products, nef / Q000235:genetics / Q000378:metabolism*; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D034622:RNA Interference / Q000502:physiology*; D012330:RNA, Double-Stranded / Q000378:metabolism / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*; D054311:nef Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; D012330:RNA, Double-Stranded; D054311:nef Gene Products, Human Immunodeficiency Virus