Disease relevance of HIV2gp6

• Here we show that certain aminoglycoside antibiotics, in particular neomycin B, can block binding of the HIV Rev protein to its viral RNA recognition element [1].
• Although nuclear export of intron-containing cellular transcripts is restricted in mammalian cells, HIV-1 has evolved the viral Rev protein to overcome this restriction for viral transcripts [2].
• Here we demonstrate that Rev protein, purified from Escherichia coli, binds in a sequence-specific manner to the RRE element in vitro [3].
• The inhibition of HIV infection in cells stably expressing a transdominant Rev protein, in the absence of any deleterious effect on T cell function, suggests that such a strategy could provide a therapeutic effect in the T lymphocytes of acquired immunodeficiency syndrome patients [4].
• Adenovirus pre-mRNA containing an RRE in the intron was spliced equally well in the absence and presence of Rev protein [5].

High impact information on HIV2gp6

• The Rev protein of HIV-1 regulates the synthesis of partially spliced forms of cytoplasmic viral mRNA by binding to a cis-acting RNA sequence, the Rev response element (RRE) [6].
• Stable expression of transdominant Rev protein in human T cells inhibits human immunodeficiency virus replication [4].
• We have addressed this issue in Xenopus laevis oocytes by microinjecting RNA molecules containing RRE along with purified recombinant Rev protein into the oocyte nuclei [5].
• The 116-amino acid Rev protein acts by binding to the Rev response element (RRE), a complex RNA stem-loop structure located within the env gene of HIV [7].
• The Rev protein of human immunodeficiency virus type 1 is a sequence-specific RNA binding protein that is essential for viral replication [8].

Chemical compound and disease context of HIV2gp6

• The human immunodeficiency virus type 1 rev protein binds with high affinity (Kd less than 1-3 nM) to a purine-rich "bubble" containing bulged GG and GUA residues on either side of a double-helical RNA stem-loop located toward the 5' end of rev-response element RNA [9].
• Specific crosslinking was demonstrated between the Rev protein of HIV-1 (as a glutathione S-transferase fusion protein) and its RNA target, the Rev-responsive element [10].
• It therefore appears that the Rev protein of EIAV, while analogous in function to Rev proteins defined in lentiviruses of primate, ovine, and caprine origin, is nevertheless distinguished by an entirely novel domain organization [11].
• Evaluation of stilbene-containing RNA RBE sequences of varying length for their ability to bind the Rev protein of HIV-1 showed that a 22-nucleotide stilbenedicarboxamide conjugate bound Rev almost as well as a 94-base fragment of the Rev Responsive Element (RRE) [12].
• This leucine-rich stretch of amino acids proved to be essential for the transactivating properties of HIV-1 Rev. Some mutants in the AD transdominantly inhibit the function of wild-type Rev protein very efficiently [13].

Biological context of HIV2gp6

• This downregulation can be counteracted by the viral Rev protein, resulting in efficient export and expression of these mRNAs [14].
• Rev activity appears to require a critical, threshold level of Rev protein expression, thus preventing entry into this late phase in cells that are unable to support efficient HIV-1 gene expression [15].
• Intermolecular binding sites of human immunodeficiency virus type 1 Rev protein determined by protein footprinting [16].
• Rev protein reentry into postmitotic nuclei was delayed until early G1 phase, but before the arrival of ribosomal protein S6 [17].
• In contrast, a trans-dominant negative Rev protein containing an inactive nuclear export signal reentered nuclei by the nonribosomal nucleolar protein pathway in late telophase, associating with PNBs and reformed nucleoli [17].

Anatomical context of HIV2gp6

• A molecular clone of the simian immunodeficiency virus SIVSMM isolate PBj14, lacking the ATG initiation codon for Rev protein (PBj-1.5), did not produce virus or large unspliced or singly spliced viral RNA upon transfection of HeLa cells [18].
• This phenotype appeared to be linked to a specific dysfunction of Rex, since the functionally equivalent Rev protein of HIV-1 was shown to be fully efficient in promoting the synthesis of HTLV-1 envelope glycoproteins in Jurkat cells [19].
• Gene therapy for AIDS using retroviral mediated gene transfer to deliver HIV-1 antisense TAR and transdominant Rev protein genes to syngeneic lymphocytes in HIV-1 infected identical twins [20].
• Interaction of human immunodeficiency virus type I Rev protein with nuclear scaffold nucleoside triphosphatase activity [21].
• Indirect immunofluorescence staining of infected cells confirmed the cytoplasmic location of visna Rev protein and could reveal in some stained cells a higher concentration of Rev at the cellular plasma membrane [22].

Associations of HIV2gp6 with chemical compounds

• However, polyarginine substitutions expanded the RNA binding specificity of the resultant mutant Rev protein [23].
• The phosphate receptor in the rev protein is shown to be exclusively serine [24].
• We have used a site-specific photocrosslinking method based on 6-thioguanosine (6-thioG) photochemistry to probe the conformation of the high-affinity binding site of RRE RNA and its interactions with Rev protein under physiological conditions [25].

Other interactions of HIV2gp6

• The model is completed by the formulation of the feedback effects of Tat protein on transcription and translation and the feedback effect of Rev protein on nuclear export [26].

Analytical, diagnostic and therapeutic context of HIV2gp6

• We could demonstrate in gel-mobility and immunoprecipitation assays that the recombinant rev protein purified from a baculovirus expression system forms a distinct and specific complex with its target RNA (rev-responsive element), a 234-nucleotide sequence within the envelope coding region of human immunodeficiency virus 1 [27].
• Recombinant Rev protein of human immunodeficiency virus type 1 has been expressed in Escherichia coli and purified by ion-exchange and gel-filtration chromatography [28].
• To study the role of the nucleolus and nucleolar proteins in Rev function, transfected COS-7 or transformed CMT3 cells expressing the Rev protein were examined for subcellular locations of Rev and other proteins using indirect immunofluorescence and immunoelectron microscopy [29].
• Intracellular immunization with RevM10, a transdominant negative form of the Rev protein, efficiently inhibits human immunodeficiency virus (HIV) replication in vitro and gene therapy protocols that use this modality are currently being evaluated in human clinical trials [30].
• The influenza virus B and C NEP proteins interact in the yeast two-hybrid assay with a subset of nucleoporins and with the Crm1 nuclear export factor and can functionally replace the effector domain from the human immunodeficiency virus type 1 Rev protein [31].

References