gag pol fusion proteins

Summary

Summary: Polyprotein products of a fused portion of retroviral mRNA containing the gag and pol genes. The polyprotein is synthesized only five percent of the time since pol is out of frame with gag, and is generated by ribosomal frameshifting.

Top Publications

  1. Louis J, Dyda F, Nashed N, Kimmel A, Davies D. Hydrophilic peptides derived from the transframe region of Gag-Pol inhibit the HIV-1 protease. Biochemistry. 1998;37:2105-10 pubmed
    ..The sequence-specific, selective inhibition of the HIV-1 protease by the viral TFP suggests a role for TFP in regulating protease function during HIV-1 replication. ..
  2. Irwin P, Voytas D. Expression and processing of proteins encoded by the Saccharomyces retrotransposon Ty5. J Virol. 2001;75:1790-7 pubmed
    ..The ratio of Ty5 Gag to Pol averaged 5:1 throughout the time course experiment, suggesting that differential protein stability regulates the amounts of these proteins. ..
  3. Hill M, Hooker C, Harrich D, Crowe S, Mak J. Gag-Pol supplied in trans is efficiently packaged and supports viral function in human immunodeficiency virus type 1. J Virol. 2001;75:6835-40 pubmed
    ..Our data show that translation of Gag and Gag-Pol from the same mRNA is not critical for virion packaging of the Gag-Pol polyprotein or for viral function. ..
  4. Wagner R, Graf M, Bieler K, Wolf H, Grunwald T, Foley P, et al. Rev-independent expression of synthetic gag-pol genes of human immunodeficiency virus type 1 and simian immunodeficiency virus: implications for the safety of lentiviral vectors. Hum Gene Ther. 2000;11:2403-13 pubmed
    ..By eliminating regions of homology and sequences involved in packaging, synthetic gag-pol genes should improve the safety profile of lentiviral vectors. ..
  5. Halwani R, Khorchid A, Cen S, Kleiman L. Rapid localization of Gag/GagPol complexes to detergent-resistant membrane during the assembly of human immunodeficiency virus type 1. J Virol. 2003;77:3973-84 pubmed
  6. Pettit S, Gulnik S, Everitt L, Kaplan A. The dimer interfaces of protease and extra-protease domains influence the activation of protease and the specificity of GagPol cleavage. J Virol. 2003;77:366-74 pubmed
    ..Assembly domains within GagPol outside the protease domain also influence enzyme activation. ..
  7. Tachedjian G, Moore K, Goff S, Sluis Cremer N. Efavirenz enhances the proteolytic processing of an HIV-1 pol polyprotein precursor and reverse transcriptase homodimer formation. FEBS Lett. 2005;579:379-84 pubmed
    ..These data suggest that potent mediators of RT dimerization might interfere with the late-stages of viral replication. ..
  8. Shehu Xhilaga M, Crowe S, Mak J. Maintenance of the Gag/Gag-Pol ratio is important for human immunodeficiency virus type 1 RNA dimerization and viral infectivity. J Virol. 2001;75:1834-41 pubmed
  9. Orlova M, Yueh A, Leung J, Goff S. Reverse transcriptase of Moloney murine leukemia virus binds to eukaryotic release factor 1 to modulate suppression of translational termination. Cell. 2003;115:319-31 pubmed
    ..These results suggest that RT enhances suppression of termination and that the interaction of RT with eRF1 is required for an appropriate level of translational readthrough. ..

More Information

Publications62

  1. de Oliveira T, Engelbrecht S, Janse van Rensburg E, Gordon M, Bishop K, zur Megede J, et al. Variability at human immunodeficiency virus type 1 subtype C protease cleavage sites: an indication of viral fitness?. J Virol. 2003;77:9422-30 pubmed
    ..Natural variation at C cleavage sites may play an important role, not only in regulation of the viral cycle but also in disease progression and response to therapy. ..
  2. Pettit S, Clemente J, Jeung J, Dunn B, Kaplan A. Ordered processing of the human immunodeficiency virus type 1 GagPol precursor is influenced by the context of the embedded viral protease. J Virol. 2005;79:10601-7 pubmed
    ..Overall, our data support a model in which the selection of processing sites and the order of precursor processing are defined, at least in part, by the structure of GagPol itself. ..
  3. Pettit S, Everitt L, Choudhury S, Dunn B, Kaplan A. Initial cleavage of the human immunodeficiency virus type 1 GagPol precursor by its activated protease occurs by an intramolecular mechanism. J Virol. 2004;78:8477-85 pubmed
    ..These intramolecular cleavages produce an extended form of PR that completes the final processing steps accompanying the final stages of particle assembly by an intermolecular mechanism. ..
  4. Sakuma R, Ohmine S, Ikeda Y. Determinants for the rhesus monkey TRIM5alpha-mediated block of the late phase of HIV-1 replication. J Biol Chem. 2010;285:3784-93 pubmed publisher
    ..RBCC domains of TRIM family proteins may play a role in sensing newly synthesized viral proteins as a part of innate immunity against viral infection. ..
  5. Guo F, Gabor J, Cen S, Hu K, Mouland A, Kleiman L. Inhibition of cellular HIV-1 protease activity by lysyl-tRNA synthetase. J Biol Chem. 2005;280:26018-23 pubmed
    ..Using a novel bioluminescence resonance energy transfer assay to directly measure HIV-1 protease activity in vivo also indicates that the overexpression of LysRS in the cell reduces viral protease activity. ..
  6. Ananworanich J, Pancharoen C, Sirivichayakul S, Buranapraditkun S, Apateerapong W, Ubolyam S, et al. Undetectable plasma HIV-1 RNA with strong gag-pol specific interferon-gamma ELISPOT response in an HIV-1 clade A/E-infected child untreated with antiretroviral therapy. Asian Pac J Allergy Immunol. 2004;22:165-9 pubmed
    ..0. DNA PCR was positive by methods using gag/pol primers but not env/pol primers. The patient had strong HIV-1-specific cytotoxic T lymphocyte responses, which likely contributed to her low viral burden and undetectable plasma HIV-1 RNA. ..
  7. Zhu Y, Planelles V. A multigene lentiviral vector system based on differential splicing. Methods Mol Med. 2003;76:433-48 pubmed
  8. Matukonis M, Li M, Molina R, Paszkiet B, Kaleko M, Luo T. Development of second- and third-generation bovine immunodeficiency virus-based gene transfer systems. Hum Gene Ther. 2002;13:1293-303 pubmed
    ..The modifications made to the packaging constructs improve the safety profile of the vector system. Finally, BIV vectors provide an alternative to human immunodeficiency virus-based gene transfer systems...
  9. Li Z, Stahl G, Farabaugh P. Programmed +1 frameshifting stimulated by complementarity between a downstream mRNA sequence and an error-correcting region of rRNA. RNA. 2001;7:275-84 pubmed
    ..Complementarity between the stimulator and a portion of the accuracy center of the ribosome, Helix 18, implies that the stimulator may directly disrupt error correction by the ribosome. ..
  10. Molina R, Ye H, Brady J, Zhang J, Zimmerman H, Kaleko M, et al. A synthetic Rev-independent bovine immunodeficiency virus-based packaging construct. Hum Gene Ther. 2004;15:865-77 pubmed
    ..Generation of the synthetic packaging construct provides further advances to the safety of lentiviral vectors for clinical applications. ..
  11. Arad G, Chorev M, Shtorch A, Goldblum A, Kotler M. Point mutation in avian sarcoma leukaemia virus protease which increases its activity but impairs infectious virus production. J Gen Virol. 1995;76 ( Pt 8):1917-25 pubmed
    ..However, this mutation reduced the production of reverse transcriptase-containing particles and infectious virus following transfection of permissive cells with virus DNA. ..
  12. Wingard J, Anderson B, Weissman D. Induction of HIV-specific T and B cell responses with a replicating and conditionally infectious lentiviral vaccine. Eur J Immunol. 2008;38:1310-20 pubmed publisher
    ..Mice developed antigen-specific T cell responses and specific antibodies after immunization. Transduction of DC with a replication-competent but conditionally infectious lentivirus could be a novel vaccine strategy for HIV. ..
  13. Graham B, Koup R, Roederer M, Bailer R, Enama M, Moodie Z, et al. Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 DNA candidate vaccine. J Infect Dis. 2006;194:1650-60 pubmed
    ..DNA vaccination induced antibody to and T cell responses against 3 major HIV-1 subtypes and will be further evaluated as a potential component of a preventive AIDS vaccine regimen. ..
  14. Chiu H, Wang F, Chen Y, Wang C. Effects of human immunodeficiency virus type 1 transframe protein p6* mutations on viral protease-mediated Gag processing. J Gen Virol. 2006;87:2041-6 pubmed
    ..However, the released virions are not processed appropriately and show a greatly reduced viral infectivity. This suggests that the p6* is indispensable during the process of PR-mediated virus particle maturation. ..
  15. Valle R, Wickner R. Elimination of L-A double-stranded RNA virus of Saccharomyces cerevisiae by expression of gag and gag-pol from an L-A cDNA clone. J Virol. 1993;67:2764-71 pubmed
    ..Our hypotheses on exclusion of L-A proteins may also apply to resistance to plant viruses produced by expression of viral replicases in transgenic plants. ..
  16. Ogg G, Kostense S, Klein M, Jurriaans S, Hamann D, McMichael A, et al. Longitudinal phenotypic analysis of human immunodeficiency virus type 1-specific cytotoxic T lymphocytes: correlation with disease progression. J Virol. 1999;73:9153-60 pubmed
    ..Overall, these data support a role of HIV-specific CTL in the control of disease progression and suggest that the ultimate loss of such CTL may be preferentially from the CD27(+) CD45RO(+) subset. ..
  17. Farson D, Witt R, McGuinness R, Dull T, Kelly M, Song J, et al. A new-generation stable inducible packaging cell line for lentiviral vectors. Hum Gene Ther. 2001;12:981-97 pubmed
    ..The packaging cell line and the assays developed will advance lentiviral vectors toward the stringent requirements of clinical applications. ..
  18. McGettigan J, Naper K, Orenstein J, Koser M, McKenna P, Schnell M. Functional human immunodeficiency virus type 1 (HIV-1) Gag-Pol or HIV-1 Gag-Pol and env expressed from a single rhabdovirus-based vaccine vector genome. J Virol. 2003;77:10889-99 pubmed
    ..This research opens up the possibility for the further improvement of rhabdovirus-based HIV-1 vaccines and their use to express large foreign proteins, perhaps from multiple human pathogens. ..
  19. Chen C, Montelaro R. Characterization of RNA elements that regulate gag-pol ribosomal frameshifting in equine infectious anemia virus. J Virol. 2003;77:10280-7 pubmed
  20. Coyle J, Guzik B, Bor Y, Jin L, Eisner Smerage L, Taylor S, et al. Sam68 enhances the cytoplasmic utilization of intron-containing RNA and is functionally regulated by the nuclear kinase Sik/BRK. Mol Cell Biol. 2003;23:92-103 pubmed
    ..They also provide further evidence of links between signal transduction and RNA utilization...
  21. Adamson C, Nermut M, Jones I. Control of human immunodeficiency virus type-1 protease activity in insect cells expressing Gag-Pol rescues assembly of immature but not mature virus-like particles. Virology. 2003;308:157-65 pubmed
    ..Our data are consistent with a requirement for specific cellular factors in addition to the correct ratio of Gag and Gag-Pol for assembly of mature retrovirus particles in heterologous cell types. ..
  22. Patel J, Wang S, Izmailova E, Aldovini A. The simian immunodeficiency virus 5' untranslated leader sequence plays a role in intracellular viral protein accumulation and in RNA packaging. J Virol. 2003;77:6284-92 pubmed
    ..This location of the SIV Psi element provides the means for efficient discrimination between viral genomic and spliced RNAs. ..
  23. L├╝tzelberger M, Reinert L, Das A, Berkhout B, Kjems J. A novel splice donor site in the gag-pol gene is required for HIV-1 RNA stability. J Biol Chem. 2006;281:18644-51 pubmed
    ..This implies that U1 small nuclear RNA binding to optimal but non-functional splice sites might have a role in protecting unspliced HIV-1 mRNA from degradation. ..
  24. Amara R, Smith J, Staprans S, Montefiori D, Villinger F, Altman J, et al. Critical role for Env as well as Gag-Pol in control of a simian-human immunodeficiency virus 89.6P challenge by a DNA prime/recombinant modified vaccinia virus Ankara vaccine. J Virol. 2002;76:6138-46 pubmed
    ..Our results highlight the importance of immune responses to Env, as well as to Gag-Pol, in the control of immunodeficiency virus challenges and the protection of CD4(+) cells. ..
  25. Palmer M, Kirkman R, Kosloff B, Eipers P, Morrow C. tRNA isoacceptor preference prior to retrovirus Gag-Pol junction links primer selection and viral translation. J Virol. 2007;81:4397-404 pubmed
    ..The results demonstrate that codon preference prior to the Gag-Pol junction influences primer selection and suggest a coordination of Gag-Pol synthesis and acquisition of the tRNA primer required for retrovirus replication. ..
  26. Uberla K, Rosenwirth B, ten Haaft P, Heeney J, Sutter G, Erfle V. Therapeutic immunization with Modified Vaccinia Virus Ankara (MVA) vaccines in SIV-infected rhesus monkeys undergoing antiretroviral therapy. J Med Primatol. 2007;36:2-9 pubmed
    ..Although a subset of animals seem to benefit from therapeutic immunization with MVA vectors, the difference in set point RNA levels between the groups did not reach statistical significance. ..
  27. Wang S, Bertley F, Kozlowski P, Herrmann L, Manson K, Mazzara G, et al. An SHIV DNA/MVA rectal vaccination in macaques provides systemic and mucosal virus-specific responses and protection against AIDS. AIDS Res Hum Retroviruses. 2004;20:846-59 pubmed
    ..In addition, the immunity achieved with this mucosal vaccination regimen is sufficient to delay progression to AIDS. ..
  28. Fuller M, Anson D. Helper plasmids for production of HIV-1-derived vectors. Hum Gene Ther. 2001;12:2081-93 pubmed
  29. Achaz G, Palmer S, Kearney M, Maldarelli F, Mellors J, Coffin J, et al. A robust measure of HIV-1 population turnover within chronically infected individuals. Mol Biol Evol. 2004;21:1902-12 pubmed
    ..The definition and interpretation of estimates of such "effective" population parameters are discussed. ..
  30. Jin L, Guzik B, Bor Y, Rekosh D, Hammarskjold M. Tap and NXT promote translation of unspliced mRNA. Genes Dev. 2003;17:3075-86 pubmed
    ..They further suggest that Tap/NXT may play a role in remodeling of cytoplasmic RNP complexes, providing a link between export pathways and cytoplasmic fate. ..
  31. Liu X, Chang L, Vigorito M, Kass M, Li H, Chang S. Methamphetamine-induced behavioral sensitization is enhanced in the HIV-1 transgenic rat. J Neuroimmune Pharmacol. 2009;4:309-16 pubmed publisher
    ..Our results indicate that METH-induced behavioral sensitization is greater in the presence of HIV infection and suggest that D1R expression in the prefrontal cortex may play a role in METH addiction in HIV-positive individuals. ..
  32. Ter Brake O, Berkhout B. Lentiviral vectors that carry anti-HIV shRNAs: problems and solutions. J Gene Med. 2007;9:743-50 pubmed
    ..The remaining targets in the vector backbone may be modified by point mutations to resist RNAi-mediated degradation during vector production. ..
  33. Campbell S, Oshima M, Mirro J, Nagashima K, Rein A. Reversal by dithiothreitol treatment of the block in murine leukemia virus maturation induced by disulfide cross-linking. J Virol. 2002;76:10050-5 pubmed
    ..This may be a useful experimental system for further analysis of retroviral maturation under controlled conditions in vitro. ..
  34. Wyatt L, Earl P, Xiao W, Americo J, Cotter C, Vogt J, et al. Elucidating and minimizing the loss by recombinant vaccinia virus of human immunodeficiency virus gene expression resulting from spontaneous mutations and positive selection. J Virol. 2009;83:7176-84 pubmed publisher
    ..Understanding the causes of instability and taking preemptive actions will facilitate the development of rMVA and other poxviruses as human and veterinary recombinant vaccines. ..
  35. Stebbins J, Towler E, Tennant M, Deckman I, Debouck C. The 80's loop (residues 78 to 85) is important for the differential activity of retroviral proteases. J Mol Biol. 1997;267:467-75 pubmed
  36. Lawler J, Merkulov G, Boeke J. Frameshift signal transplantation and the unambiguous analysis of mutations in the yeast retrotransposon Ty1 Gag-Pol overlap region. J Virol. 2001;75:6769-75 pubmed
    ..This work defines the amino terminus of the Ty1 PR and introduces a new technique for studying viral genome organization. ..
  37. zur Megede J, Otten G, Doe B, Liu H, Leung L, Ulmer J, et al. Expression and immunogenicity of sequence-modified human immunodeficiency virus type 1 subtype B pol and gagpol DNA vaccines. J Virol. 2003;77:6197-207 pubmed
    ..These results support the inclusion of a gagpol in-frame fusion gene in future HIV vaccine approaches. ..
  38. Costa L, Zheng Y, Sabotic J, Mak J, Fackler O, Peterlin B. Nef binds p6* in GagPol during replication of human immunodeficiency virus type 1. J Virol. 2004;78:5311-23 pubmed
    ..Our data demonstrate that the retention of Nef in the intermediate compartment interferes with viral replication and suggest a new role for Nef in the production of HIV-1. ..
  39. Luo K, Liu B, Xiao Z, Yu Y, Yu X, Gorelick R, et al. Amino-terminal region of the human immunodeficiency virus type 1 nucleocapsid is required for human APOBEC3G packaging. J Virol. 2004;78:11841-52 pubmed
    ..These results suggest that the N-terminal region of HIV-1 NC, which is critical for binding to RNA and mediating Gag-Gag oligomerization, plays an important role in APOBEC3G binding and virion packaging. ..
  40. Laeyendecker O, Zhang G, Quinn T, Garten R, Ray S, Lai S, et al. Molecular epidemiology of HIV-1 subtypes in southern China. J Acquir Immune Defic Syndr. 2005;38:356-62 pubmed
  41. Brunelle M, Brakier Gingras L, Lemay G. Replacement of murine leukemia virus readthrough mechanism by human immunodeficiency virus frameshift allows synthesis of viral proteins and virus replication. J Virol. 2003;77:3345-50 pubmed
    ..This system could be a most interesting alternative to study ribosomal frameshift in the context of a virus amenable to the use of a simple animal model. ..
  42. Singh R, Barry M. Repertoire and immunofocusing of CD8 T cell responses generated by HIV-1 gag-pol and expression library immunization vaccines. J Immunol. 2004;173:4387-93 pubmed
    ..In contrast, the genetically re-engineered ELI vaccine appears to better maintain the multivalent CD8 responses that may be required to control HIV-1 viral variants. ..
  43. Gabor J, Cen S, Javanbakht H, Niu M, Kleiman L. Effect of altering the tRNA(Lys)(3) concentration in human immunodeficiency virus type 1 upon its annealing to viral RNA, GagPol incorporation, and viral infectivity. J Virol. 2002;76:9096-102 pubmed
    ..This result indicates that GagPol, whose interaction is required during packaging, is not a limiting factor during tRNA(Lys) incorporation into HIV-1, whereas LysRS is. ..
  44. Hull S, Boris Lawrie K. Analysis of synergy between divergent simple retrovirus posttranscriptional control elements. Virology. 2003;317:146-54 pubmed
    ..Our results uncovered a previously unidentified role of CTE in conjunction with Tap and NXT1 in commitment to efficient cytoplasmic RNA utilization...
  45. Priddy F, Brown D, Kublin J, Monahan K, Wright D, Lalezari J, et al. Safety and immunogenicity of a replication-incompetent adenovirus type 5 HIV-1 clade B gag/pol/nef vaccine in healthy adults. Clin Infect Dis. 2008;46:1769-81 pubmed publisher
    ..Despite these findings, vaccination in a proof-of-concept trial with use of this vaccine was discontinued because of lack of efficacy. ..
  46. Kleiman L, Cen S. The tRNALys packaging complex in HIV-1. Int J Biochem Cell Biol. 2004;36:1776-86 pubmed
    ..While tRNALys incorporation into viruses depends upon its interaction with LysRS, tRNALys aminoacylation is not a requirement for viral packaging. ..
  47. Figueiredo A, Moore K, Mak J, Sluis Cremer N, de B├ęthune M, Tachedjian G. Potent nonnucleoside reverse transcriptase inhibitors target HIV-1 Gag-Pol. PLoS Pathog. 2006;2:e119 pubmed
    ..Furthermore, these drugs can serve as useful probes to further understand processes involved in HIV-1 particle assembly and maturation. ..
  48. Sei S, Yang Q, O NEILL D, Yoshimura K, Nagashima K, Mitsuya H. Identification of a key target sequence to block human immunodeficiency virus type 1 replication within the gag-pol transframe domain. J Virol. 2000;74:4621-33 pubmed
  49. Koldej R, Cmielewski P, Stocker A, Parsons D, Anson D. Optimisation of a multipartite human immunodeficiency virus based vector system; control of virus infectivity and large-scale production. J Gene Med. 2005;7:1390-9 pubmed
    ..By taking a systematic approach to optimising all aspects of our five-plasmid lentiviral vector system we improved titre, safety, large-scale production, and demonstrated that infectivity could be specifically controlled. ..
  50. Han X, Dai D, Zhang M, Wang Y, Jiang Y, Shang H. [Study on gag-pol region characteristics of HIV-1 strains epidemic in Liaoning province]. Zhonghua Yi Xue Za Zhi. 2007;87:1966-70 pubmed
    ..CRF07_BC and CRF08_BC were the youngest strains transmitted to Liaoning province and showed strong founder effect. ..
  51. Kappes J, Wu X, Wakefield J. Production of trans-lentiviral vector with predictable safety. Methods Mol Med. 2003;76:449-65 pubmed
  52. Otten G, Schaefer M, Doe B, Liu H, Megede J, Donnelly J, et al. Potent immunogenicity of an HIV-1 gag-pol fusion DNA vaccine delivered by in vivo electroporation. Vaccine. 2006;24:4503-9 pubmed
  53. Bittner A, Mitnacht Kraus R, Schnierle B. Specific transduction of HIV-1 envelope expressing cells by retroviral vectors pseudotyped with hybrid CD4/CXCR4 receptors. J Virol Methods. 2002;104:83-92 pubmed
    ..Thus, CD4-D4-CXCR4 hybrids are useful for the generation of retroviral and lentiviral vectors with specificity for HIV-1 envelope expressing cells. ..