title: Expression of the human immunodeficiency virus type 1 primer binding sequence inhibits HIV-1 replication.
abstract: Optimal targets for anti-human immunodeficiency virus (HIV) moieties are those regions of the viral genome that are greatly conserved. The primer binding site (PBS) of HIV is an 18-nucleotide sequence complementary to the 3' end of tRNA(Lys3) that serves as the primer for HIV-1 reverse transcription. All HIV-1 isolates analyzed to date contain a PBS complementary to tRNA(Lys3) illustrating the conservation of this sequence. We investigated the activity of a hammerhead ribozyme targeting the PBS of HIV-1. CEMss cells transduced with retroviral vectors containing either the PBS hammerhead ribozyme or its complementary sequence (as a control) in the R region of the vector long terminal repeat (LTR) were challenged with HIV-1NL4-3. Surprisingly >80% inhibition of HIV-1 production was observed with the vector containing the (control) sequence complementary to the PBS ribozyme. We propose that the LTR-driven vector transcript containing 18 nucleotides identical to the HIV-1 PBS may act like an RNA decoy to titrate viral proteins such as reverse transcriptase and nucleocapsid away from genuine viral transcripts, thus compromising virus replication.
authors.affiliation: Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Kechli
authors.forename: P J
authors.initials: PJ
authors.lastname: Freiden
authors.forename: J J
authors.initials: JJ
authors.lastname: Rossi
authors.forename: M K
authors.initials: MK
authors.lastname: Brenner
authors.forename: M A
authors.initials: MA
authors.lastname: Choueiry
authors.forename: J V
authors.initials: JV
authors.lastname: Garcia
authors.forename: K S
authors.initials: KS
authors.lastname: Slobod
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D005822:Genetic Vectors / Q000235:genetics; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000235:genetics; D009414:Nerve Growth Factors / Q000235:genetics; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D016337:RNA, Catalytic / Q000235:genetics*; D012346:RNA, Transfer, Amino Acyl / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D014779:Virus Replication / Q000235:genetics*
chemical_list: D016655:HIV Core Protein p24; D009414:Nerve Growth Factors; C034477:RNA primers; D016337:RNA, Catalytic; D012346:RNA, Transfer, Amino Acyl; D012367:RNA, Viral; D012313:RNA