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Gene Review

gag-pol  -  Gag-Pol

Simian immunodeficiency virus

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Disease relevance of gag-pol

  • The dynamics of plasma viremia were explored in a group of 12 simian immunodeficiency virus (SIV)-infected rhesus macaques (Macaca mulatta) that had received prior immunization with either nonrecombinant or trivalent (gag-pol, env) SIV-recombinant vaccinia viruses [1].
  • Cynomolgus macaques were immunized intramuscularly with modified vaccinia virus Ankara (MVA) expressing the SIVsm env and gag-pol genes (MVA-SIVsm) at 0 and 3 months (n=4), at 0, 3 and 8 months (n=4) or at 0 and 3 months followed by purified native SIVsm gp148 and recombinant SIVmac p27 in immunostimulatory complexes at 8 months (n=4) [2].
  • In this study, the ability of a recombinant canarypox virus expressing SIV Gag-Pol-Env (ALVAC/SIV gag-pol-env) was assessed for its ability to elicit both dominant and subdominant epitope-specific CTL responses in rhesus monkeys [3].
  • Both the HIV-1 and the SIV synthetic gag-pol expression plasmids could mediate transduction of an SIV vector into nondividing human cells with titers of about 10(6) transducing units/ml [4].
  • Rhesus macaques were immunized with a replication-deficient vaccinia virus (MVA) expressing human immunodeficiency virus type 1 89.6 envelope (env) and SIV gagpol (MVA/SHIV89.6) with or without a protein boost consisting of soluble 89.6 env (gp140) [5].

High impact information on gag-pol


Biological context of gag-pol

  • The immunogenicity and protective efficacy of a modified vaccinia virus Ankara (MVA) recombinant expressing the simian immunodeficiency virus (SIV) Gag-Pol proteins (MVA-gag-pol) was explored in rhesus monkeys expressing the major histocompatibility complex (MHC) class I allele, MamuA*01 [10].
  • Although cis incorporation has been already demonstrated for Gag, the novelty of these findings is that newly acquired resistant mutations in Gag-Pol will select their specific genomic RNA during virus replication, thus rapidly increasing the chance of the emergence of resistant viruses during the course of anti-retroviral treatment [11].
  • Although Gag alone is sufficient for the incorporation of vRNA into virus particles, Gag-Pol molecules play an important role in vRNA dimerization and virion maturation [11].
  • CONCLUSION: This new non-reciprocal cross packaging relationship between SIV and HIV-2 provides a novel way of significantly increasing bio-safety with a reduced sequence homology between the HIV-2 gene transfer vector and the SIV Gag-Pol construct thus ensuring that vector RNA packaging is unidirectional [12].

Analytical, diagnostic and therapeutic context of gag-pol

  • Anti-vector immunity induced by this immunization was shown to prevent the efficient stimulation of CTL directed to the cognate Gag epitope, p11C C-M, following vaccination with another MVA construct expressing SIV Gag-Pol under a strong synthetic vaccinia virus-specific promoter [13].
  • An unexpected packaging relationship was found to exist between HIV-2 and SIV with SIV Gag-Pol able to package HIV-2 vector RNA and transduce dividing SV2T cells and CNS cell cultures with an efficiency equivalent to the homologous HIV-1 vector however HIV-2 was unable to deliver SIV based vectors [12].


  1. Patterns of viral replication correlate with outcome in simian immunodeficiency virus (SIV)-infected macaques: effect of prior immunization with a trivalent SIV vaccine in modified vaccinia virus Ankara. Hirsch, V.M., Fuerst, T.R., Sutter, G., Carroll, M.W., Yang, L.C., Goldstein, S., Piatak, M., Elkins, W.R., Alvord, W.G., Montefiori, D.C., Moss, B., Lifson, J.D. J. Virol. (1996) [Pubmed]
  2. Immunization with recombinant modified vaccinia virus Ankara can modify mucosal simian immunodeficiency virus infection and delay disease progression in macaques. Nilsson, C., Sutter, G., Walther-Jallow, L., ten Haaft, P., Akerblom, L., Heeney, J., Erfle, V., Böttiger, P., Biberfeld, G., Thorstensson, R. J. Gen. Virol. (2002) [Pubmed]
  3. Recombinant canarypox vaccine-elicited CTL specific for dominant and subdominant simian immunodeficiency virus epitopes in rhesus monkeys. Santra, S., Schmitz, J.E., Kuroda, M.J., Lifton, M.A., Nickerson, C.E., Lord, C.I., Pal, R., Franchini, G., Letvin, N.L. J. Immunol. (2002) [Pubmed]
  4. 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. Wagner, R., Graf, M., Bieler, K., Wolf, H., Grunwald, T., Foley, P., Uberla, K. Hum. Gene Ther. (2000) [Pubmed]
  5. Comparison of vaccine strategies using recombinant env-gag-pol MVA with or without an oligomeric Env protein boost in the SHIV rhesus macaque model. Earl, P.L., Wyatt, L.S., Montefiori, D.C., Bilska, M., Woodward, R., Markham, P.D., Malley, J.D., Vogel, T.U., Allen, T.M., Watkins, D.I., Miller, N., Moss, B. Virology (2002) [Pubmed]
  6. A novel splice donor site in the gag-pol gene is required for HIV-1 RNA stability. Lützelberger, M., Reinert, L.S., Das, A.T., Berkhout, B., Kjems, J. J. Biol. Chem. (2006) [Pubmed]
  7. In vitro characterization of the interaction between HIV-1 Gag and human lysyl-tRNA synthetase. Kovaleski, B.J., Kennedy, R., Hong, M.K., Datta, S.A., Kleiman, L., Rein, A., Musier-Forsyth, K. J. Biol. Chem. (2006) [Pubmed]
  8. A trans-lentiviral packaging cell line for high-titer conditional self-inactivating HIV-1 vectors. Cockrell, A.S., Ma, H., Fu, K., McCown, T.J., Kafri, T. Mol. Ther. (2006) [Pubmed]
  9. Comparative efficacy of recombinant modified vaccinia virus Ankara expressing simian immunodeficiency virus (SIV) Gag-Pol and/or Env in macaques challenged with pathogenic SIV. Ourmanov, I., Brown, C.R., Moss, B., Carroll, M., Wyatt, L., Pletneva, L., Goldstein, S., Venzon, D., Hirsch, V.M. J. Virol. (2000) [Pubmed]
  10. Immunization with a modified vaccinia virus expressing simian immunodeficiency virus (SIV) Gag-Pol primes for an anamnestic Gag-specific cytotoxic T-lymphocyte response and is associated with reduction of viremia after SIV challenge. Seth, A., Ourmanov, I., Schmitz, J.E., Kuroda, M.J., Lifton, M.A., Nickerson, C.E., Wyatt, L., Carroll, M., Moss, B., Venzon, D., Letvin, N.L., Hirsch, V.M. J. Virol. (2000) [Pubmed]
  11. Gag-Pol bearing a reverse transcriptase drug-resistant mutation influences viral genomic RNA incorporation into human immunodeficiency virus type 1 particles. Aguiar, R.S., Pereira, H.S., Costa, L.J., Brindeiro, R.M., Tanuri, A. J. Gen. Virol. (2006) [Pubmed]
  12. Identification of unique reciprocal and non reciprocal cross packaging relationships between HIV-1, HIV-2 and SIV reveals an efficient SIV/HIV-2 lentiviral vector system with highly favourable features for in vivo testing and clinical usage. Strappe, P.M., Hampton, D.W., Brown, D., Cachon-Gonzalez, B., Caldwell, M., Fawcett, J.W., Lever, A.M. Retrovirology (2005) [Pubmed]
  13. Induction of simian immunodeficiency virus (SIV)-specific CTL in rhesus macaques by vaccination with modified vaccinia virus Ankara expressing SIV transgenes: influence of pre-existing anti-vector immunity. Sharpe, S., Polyanskaya, N., Dennis, M., Sutter, G., Hanke, T., Erfle, V., Hirsch, V., Cranage, M. J. Gen. Virol. (2001) [Pubmed]
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