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Gene Review

gag-pol  -  Gag-Pol

Human immunodeficiency virus 1

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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


Anatomical context of gag-pol


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].


  1. Identification of a key target sequence to block human immunodeficiency virus type 1 replication within the gag-pol transframe domain. Sei, S., Yang, Q.E., O'Neill, D., Yoshimura, K., Nagashima, K., Mitsuya, H. J. Virol. (2000) [Pubmed]
  2. Incorporation of functional human immunodeficiency virus type 1 integrase into virions independent of the Gag-Pol precursor protein. Liu, H., Wu, X., Xiao, H., Conway, J.A., Kappes, J.C. J. Virol. (1997) [Pubmed]
  3. Human immunodeficiency virus type 1 integrase protein promotes reverse transcription through specific interactions with the nucleoprotein reverse transcription complex. Wu, X., Liu, H., Xiao, H., Conway, J.A., Hehl, E., Kalpana, G.V., Prasad, V., Kappes, J.C. J. Virol. (1999) [Pubmed]
  4. Inhibition of HIV-1 virion production by a transdominant mutant of integrase interactor 1. Yung, E., Sorin, M., Pal, A., Craig, E., Morozov, A., Delattre, O., Kappes, J., Ott, D., Kalpana, G.V. Nat. Med. (2001) [Pubmed]
  5. Characterization of ribosomal frameshifting in HIV-1 gag-pol expression. Jacks, T., Power, M.D., Masiarz, F.R., Luciw, P.A., Barr, P.J., Varmus, H.E. Nature (1988) [Pubmed]
  6. Complementation of integrase function in HIV-1 virions. Fletcher, T.M., Soares, M.A., McPhearson, S., Hui, H., Wiskerchen, M., Muesing, M.A., Shaw, G.M., Leavitt, A.D., Boeke, J.D., Hahn, B.H. EMBO J. (1997) [Pubmed]
  7. The cellular HIV-1 Rev cofactor hRIP is required for viral replication. Yu, Z., Sánchez-Velar, N., Catrina, I.E., Kittler, E.L., Udofia, E.B., Zapp, M.L. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  8. 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. Seth, A., Ourmanov, I., Kuroda, M.J., Schmitz, J.E., Carroll, M.W., Wyatt, L.S., Moss, B., Forman, M.A., Hirsch, V.M., Letvin, N.L. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  9. In vivo processing of Pr160gag-pol from human immunodeficiency virus type 1 (HIV) in acutely infected, cultured human T-lymphocytes. Lindhofer, H., von der Helm, K., Nitschko, H. Virology (1995) [Pubmed]
  10. An inhibitor of the protease blocks maturation of human and simian immunodeficiency viruses and spread of infection. Ashorn, P., McQuade, T.J., Thaisrivongs, S., Tomasselli, A.G., Tarpley, W.G., Moss, B. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  11. Saquinavir. Clinical pharmacology and efficacy. Vella, S., Floridia, M. Clinical pharmacokinetics. (1998) [Pubmed]
  12. Molecular basis of resistance to HIV-1 protease inhibition: a plausible hypothesis. Luque, I., Todd, M.J., Gómez, J., Semo, N., Freire, E. Biochemistry (1998) [Pubmed]
  13. Binding of oligopyrimidines to the RNA hairpin responsible for the ribosome gag-pol frameshift in HIV-1. Aupeix, K., Le Tinévez, R., Toulmé, J.J. FEBS Lett. (1999) [Pubmed]
  14. Evidence for the differential effects of nucleocapsid protein on strand transfer in various regions of the HIV genome. Derebail, S.S., Heath, M.J., DeStefano, J.J. J. Biol. Chem. (2003) [Pubmed]
  15. Helper plasmids for production of HIV-1-derived vectors. Fuller, M., Anson, D.S. Hum. Gene Ther. (2001) [Pubmed]
  16. Potent immunogenicity of an HIV-1 gag-pol fusion DNA vaccine delivered by in vivo electroporation. Otten, G.R., Schaefer, M., Doe, B., Liu, H., Megede, J.Z., Donnelly, J., Rabussay, D., Barnett, S., Ulmer, J.B. Vaccine (2006) [Pubmed]
  17. Contribution of the Gag-Pol transframe domain p6* and its coding sequence to morphogenesis and replication of human immunodeficiency virus type 1. Paulus, C., Ludwig, C., Wagner, R. Virology (2004) [Pubmed]
  18. Phosphorylation of HIV-1 gag proteins by protein kinase C. Burnette, B., Yu, G., Felsted, R.L. J. Biol. Chem. (1993) [Pubmed]
  19. The function of a ribosomal frameshifting signal from human immunodeficiency virus-1 in Escherichia coli. Yelverton, E., Lindsley, D., Yamauchi, P., Gallant, J.A. Mol. Microbiol. (1994) [Pubmed]
  20. Persistence of intracellular HIV-1 mRNA correlates with HIV-1-specific immune responses in infected subjects on stable HAART. Patterson, B.K., McCallister, S., Schutz, M., Siegel, J.N., Shults, K., Flener, Z., Landay, A. AIDS (2001) [Pubmed]
  21. Cell-associated HIV-1 messenger RNA and DNA in T-helper cell and monocytes in asymptomatic HIV-1-infected subjects on HAART plus an inactivated HIV-1 immunogen. Patterson, B.K., Carlo, D.J., Kaplan, M.H., Marecki, M., Pawha, S., Moss, R.B. AIDS (1999) [Pubmed]
  22. Structure of HOE/BAY 793 complexed to human immunodeficiency virus (HIV-1) protease in two different crystal forms--structure/function relationship and influence of crystal packing. Lange-Savage, G., Berchtold, H., Liesum, A., Budt, K.H., Peyman, A., Knolle, J., Sedlacek, J., Fabry, M., Hilgenfeld, R. Eur. J. Biochem. (1997) [Pubmed]
  23. Role of RNA in facilitating Gag/Gag-Pol interaction. Khorchid, A., Halwani, R., Wainberg, M.A., Kleiman, L. J. Virol. (2002) [Pubmed]
  24. Linker insertion mutations in the human immunodeficiency virus type 1 gag gene: effects on virion particle assembly, release, and infectivity. Reicin, A.S., Paik, S., Berkowitz, R.D., Luban, J., Lowy, I., Goff, S.P. J. Virol. (1995) [Pubmed]
  25. Rapid phenotypic assay for human immunodeficiency virus type 1 protease using in vitro translation. Iga, M., Matsuda, Z., Okayama, A., Sugiura, W., Hashida, S., Morishita, K., Nagai, Y., Tsubouchi, H. J. Virol. Methods (2002) [Pubmed]
  26. Phase 1 Safety and Immunogenicity Evaluation of a Multiclade HIV-1 DNA Candidate Vaccine. Graham, B.S., Koup, R.A., Roederer, M., Bailer, R.T., Enama, M.E., Moodie, Z., Martin, J.E., McCluskey, M.M., Chakrabarti, B.K., Lamoreaux, L., Andrews, C.A., Gomez, P.L., Mascola, J.R., Nabel, G.J. J. Infect. Dis. (2006) [Pubmed]
  27. Interaction of human immunodeficiency virus type 1 Vif with Gag and Gag-Pol precursors: co-encapsidation and interference with viral protease-mediated Gag processing. Bardy, M., Gay, B., Pébernard, S., Chazal, N., Courcoul, M., Vigne, R., Decroly, E., Boulanger, P. J. Gen. Virol. (2001) [Pubmed]
  28. Cells surviving infection by human immunodeficiency virus type 1: vif or vpu mutants produce non-infectious or markedly less cytopathic viruses. Kishi, M., Nishino, Y., Sumiya, M., Ohki, K., Kimura, T., Goto, T., Nakai, M., Kakinuma, M., Ikuta, K. J. Gen. Virol. (1992) [Pubmed]
  29. A new-generation stable inducible packaging cell line for lentiviral vectors. Farson, D., Witt, R., McGuinness, R., Dull, T., Kelly, M., Song, J., Radeke, R., Bukovsky, A., Consiglio, A., Naldini, L. Hum. Gene Ther. (2001) [Pubmed]
  30. Discovery and analysis of a series of C2-symmetric HIV-1 proteinase inhibitors derived from penicillin. Gray, N.M., Cameron, J.M., Cammack, N., Cobley, K.N., Holmes, D.S., Humber, D.C., Orr, D.C., Penn, C.R., Potter, R., Madar, S. Anal. Biochem. (1994) [Pubmed]
  31. Memory CD4(+) T cells are the earliest detectable human immunodeficiency virus type 1 (HIV-1)-infected cells in the female genital mucosal tissue during HIV-1 transmission in an organ culture system. Gupta, P., Collins, K.B., Ratner, D., Watkins, S., Naus, G.J., Landers, D.V., Patterson, B.K. J. Virol. (2002) [Pubmed]
  32. Cross-packaging of human immunodeficiency virus type 1 vector RNA by spleen necrosis virus proteins: construction of a new generation of spleen necrosis virus-derived retroviral vectors. Parveen, Z., Mukhtar, M., Goodrich, A., Acheampong, E., Dornburg, R., Pomerantz, R.J. J. Virol. (2004) [Pubmed]
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