Disease relevance of gag-pol

• This particular segment of the gag-pol transframe gene appears to offer a distinctive advantage over other regions in invading viral structural genes and restraining HIV-1 replication in infected cells and may potentially be exploited as a novel antiviral genetic target [1].
• Identification of a key target sequence to block human immunodeficiency virus type 1 replication within the gag-pol transframe domain [1].
• Retroviral integrase (IN) is expressed and incorporated into virions as part of the Gag-Pol polyprotein precursor [2].
• It is unknown whether the scheme, conserved among retroviruses, for expressing and incorporating IN as a component of the Gag-Pol precursor protein is necessary for its function in the infected cell after viral entry [2].
• Since IN is expressed and assembled into virions as part of the 160-kDa Gag-Pol precursor polyprotein and catalyzes integration of the provirus in infected cells as a mature 32-kDa protein, mutations in IN are pleiotropic and may affect virus replication at different stages of the virus life cycle in addition to integration [3].

High impact information on gag-pol

• These results indicate that INI1 is required for late events in the viral life cycle, and that ectopic expression of S6 inhibits HIV-1 replication in a transdominant manner via its specific interaction with integrase within the context of Gag-Pol, providing a novel strategy to control HIV-1 replication [4].
• Characterization of ribosomal frameshifting in HIV-1 gag-pol expression [5].
• Using this approach we found that (i) Vpr-linked IN is efficiently packaged into virions independent of the Gag-Pol polyprotein, (ii) fusion proteins containing a natural RT/IN processing site are cleaved by the viral protease and (iii) only the cleaved IN protein complements IN-defective HIV-1 efficiently [6].
• The HIV-1 Rev protein facilitates the cytoplasmic accumulation of the intron-containing viral gag-pol and env mRNAs and is required for viral replication [7].
• Recombinant modified vaccinia virus Ankara-simian immunodeficiency virus gag pol elicits cytotoxic T lymphocytes in rhesus monkeys detected by a major histocompatibility complex class I/peptide tetramer [8].

Chemical compound and disease context of gag-pol

• A potent inhibitor of the HIV protease (PR), Ro 31-8959, was employed to block cleavage by the mature PR, thus allowing insights into initial stages of the gag-pol (auto)-catalytical processing [9].
• We have prepared a peptidomimetic inhibitor, U-75875, that inhibited HIV-1 gag-pol protein processing in an essentially irreversible manner [10].
• As with other HIV protease inhibitors, saquinavir inhibits the cleavage of the gag-pol protein substrate leading to the release of structurally defective and functionally inactive viral particles [11].
• The binding thermodynamics of the HIV-1 protease inhibitor acetyl pepstatin and the substrate Val-Ser-Gln-Asn-Tyr-Pro-Ile-Val-Gln, corresponding to one of the cleavage sites in the gag, gag-pol polyproteins, have been measured by direct microcalorimetric analysis [12].
• The 12 bp stem of the RNA hairpin responsible for the gag-pol frameshifting of the ribosomes during translation of the polycistronic HIV-1 mRNA has a pyrimidine-rich 5' strand and, consequently, a purine-rich 3' strand [13].

Biological context of gag-pol

• Strand transfer in highly structured nucleic acid species from the U3 3' long terminal repeats, gag-pol frameshift region, and Rev response element were strongly enhanced by NC [14].
• Codon optimization of gag-pol also reduces sequence homology with vectors containing gag gene sequences, which results in reduced transfer of biologically active gag-pol sequences to transduced cells [15].
• The gag-pol fusion plasmid was as immunogenic as the plasmid mixtures [16].
• Moreover, they validate a novel approach that obviates the need to mutate Gag-Pol in order to study the role of its individual mature components at the virus replication level [3].
• Contribution of the Gag-Pol transframe domain p6* and its coding sequence to morphogenesis and replication of human immunodeficiency virus type 1 [17].

Anatomical context of gag-pol

• Thus, DNA vaccination by intramuscular electroporation was an effective means for inducing high levels of Gag- and Pol-specific T cells, and a single gag-pol fusion DNA vaccine was sufficient for eliciting immune responses against both antigens [16].
• Phosphorylation of p17gag and Pr55gag was studied in vivo by infecting COS-7 cells with a recombinant vaccinia virus containing the HIV-1 gag-pol gene [18].
• A 15-17 nucleotide sequence from the gag-pol ribosome frameshift site of HIV-1 directs analogous ribosomal frameshifting in Escherichia coli [19].
• The two-sided Wilcoxon test (continuity correction, 0.5) was used to compare lymphocyte phenotypes, lymphoproliferative assay responses, intracellular gag-pol mRNA, lowest CD4 counts and CD4% of these two groups [20].
• Decreases in HIV-1 gag-pol mRNA+ monocytes were observed in the immunogen plus HAART group compared with the IFA plus HAART group [21].

Associations of gag-pol with chemical compounds

• The enzyme functions as a C2-symmetric dimer, cleaving the gag and gag-pol viral polyproteins at distinct sites [22].
• Exposure of cells to 1% Triton X-100 releases Gag/Gag-Pol from bulk membrane, but the complexes remain pelletable [23].
• These particles contained the Env glycoprotein, viral genomic RNA, and the mature products of the Gag and Gag-Pol polyproteins, yet they were noninfectious or poorly infectious [24].
• Using the Gag-Pol substrate as the target, the indinavir-resistant mutant V82F was evaluated further [25].

Other interactions of gag-pol

• VRC-HIVDNA009-00-VP is a 4-plasmid mixture encoding subtype B Gag-Pol-Nef fusion protein and modified envelope (Env) constructs from subtypes A, B, and C. Fifty healthy, uninfected adults were randomized to receive either placebo (n=10) or study vaccine at 2 mg (n=5), 4 mg (n=20), or 8 mg (n=15) by needle-free intramuscular injection [26].
• Interaction of human immunodeficiency virus type 1 Vif with Gag and Gag-Pol precursors: co-encapsidation and interference with viral protease-mediated Gag processing [27].
• Northern and Southern blot analyses revealed no apparent deletion in the proviral DNA and mRNA prepared from these clones, except in the case of type I and II clones isolated from M10/vpu- which contained large deletions in the mRNAs for gag and gag-pol proteins [28].
• To allow safe production of vector, a minimal packaging construct carrying only the coding sequences of the HIV-1 gag-pol, tat, and rev genes was stably introduced into 293G cells under the control of a Tet(o) minimal promoter [29].

Analytical, diagnostic and therapeutic context of gag-pol

• Potent immunogenicity of an HIV-1 gag-pol fusion DNA vaccine delivered by in vivo electroporation [16].
• Comparative analysis of the mutant proviral clones in different cell culture systems revealed that mutations within the well-conserved amino-terminal p6* region modified the Gag/Gag-Pol ratio and thus resulted in the release of viruses with impaired infectivity [17].
• In order to identify a suitable peptide substrate for human immunodeficiency virus-1 (HIV-1) proteinase, a range of peptides from various cleavage sites within the gag-pol polyprotein were assayed by HPLC for specific cleavage [30].
• Multicolor laser confocal microscopy demonstrated a globular distribution of HIV-1 gag-pol mRNA in the cytoplasm, and the distribution of CD4 and the CD45RO isoform was irregular on the cellular membrane [31].
• We also constructed SNV-based gag-pol chimeric variants by replacing the SNV integrase with the HIV-1 integrase, based on multiple sequence alignments and domain analyses [32].

References