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Gene Review

rev  -  p19

Human immunodeficiency virus 1

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Disease relevance of rev

  • This genetic complementation by rex is adequate for the rescue of a replication-defective rev mutant of HIV-1 [1].
  • Each virus also produces a second trans-acting protein that induces the expression of the unspliced messenger RNAs encoding the viral structural proteins (rev in HIV and rex in HTLV) [1].
  • Here we show that the rex protein of HTLV-I can functionally replace the rev protein of HIV-1 in transient expression assays [1].
  • This unexpected shared function between the structurally distinct rex and rev proteins emphasizes the importance of this highly conserved pathway for the regulation of human retrovirus gene expression [1].
  • This third-generation lentivirus vector uses only a fractional set of HIV genes: gag, pol, and rev [2].

Psychiatry related information on rev

  • This conclusion, taken together with the observed permissiveness of a variety of eukaryotic cell types for Rev function, suggests that the target for the activation domain of Rev is likely to be a highly conserved cellular protein(s) intrinsic to nuclear mRNA transport or splicing [3].

High impact information on rev


Chemical compound and disease context of rev


Biological context of rev

  • The SIV packaging plasmid was also modified with regard to the requirement for RRE and rev [12].
  • Most detailed analyses of the human immunodeficiency virus type 1 (HIV-1) rev gene product have relied on transfection of subgenomic env constructs into cells in which amplification of the transfected DNA occurs [13].
  • Despite encoding full-length open reading frames for gp120 and gp41 and the second coding exon of tat and rev, each chimera was replication defective [14].
  • Similarly, mutagenesis of rev codon 78 of NL4-3 from Leu to Ile partially attenuated this virus [14].
  • In addition to the structural genes, HIV contains two regulatory genes, tat and rev, that are essential for HIV replication, and four accessory genes that encode critical virulence factors [2].

Anatomical context of rev


Associations of rev with chemical compounds

  • This correlated with increased usage of the four most 3' branch points, which include those within the rev 3' splice site AG dinucleotides [19].
  • Binding of the Rev arginine rich motif to the RRE was reduced in the presence of wild-type PRMT6, whereas mutant PRMT6 did not exert this negative effect [8].
  • In addition, diminished interactions between viral RNA and mutant Rev proteins were observed, due to the introduction of single arginine to lysine substitutions in the Rev arginine rich motif [8].
  • This model system can be used to evaluate the efficacy of anti-HIV-1 vaccines directed at the envelope glycoproteins, anti-HIV-1 envelope glycoprotein antiserum or monoclonal antibodies, and anti-HIV-1 drugs designed to inhibit the tat, rev, or env functions [20].
  • In marked contrast to this, ribozyme cleaved RNA accumulated almost exclusively (n/c ratio of 28) in the nucleus in the presence of Rev. Actinomycin D time course analysis suggested that the low levels of the cytoplasmic ribozyme-cleaved RNAs in both the presence and absence of Rev were due to serve export deficiency of ribozyme-cleaved RNA [21].

Physical interactions of rev

  • Here we show that this Rev response requires a specific target sequence which coincides with a complex RNA secondary structure present in the env gene [22].
  • Here, we confirm that fusion of Tat to the RNA-binding domain of the HIV-1 Rev protein permits the efficient activation of an HIV-1 long terminal repeat (LTR) promoter in which critical TAR sequences have been replaced by RNA sequences derived from the HIV-1 Rev response element (RRE) [23].

Regulatory relationships of rev

  • Therefore, Rev down regulates its own expression and the expression of Tat and Nef [24].
  • We examined whether the codon bias observed in the vpu and vif genes relative to highly expressed human genes contributes to the Rev dependence and low expression level outside the context of the viral genome [25].
  • Similarly, cells transduced with LrevSN were able to rescue a rev- HIV-1 provirus, indicating the presence of a functional Rev. We also used LnefSN to obtain clones of cells expressing Nef [26].
  • In the nuclear expression system, Rev enhanced env mRNA transport by about 1.6-fold, while translation of this mRNA was increased more than a 100-fold [27].

Other interactions of rev

  • Tat and rev appear to be prototypes of novel eukaryotic regulatory proteins [28].
  • In support of this possibility, mutations at rev 3' splice site A4b AG dinucleotide dramatically increased splicing of the env/nef 3' splice site A5 [19].
  • Single point mutation of M1 within an infectious molecular clone is detrimental for HIV-1 exon 2 recognition without affecting Rev-dependent vif expression [9].

Analytical, diagnostic and therapeutic context of rev


  1. Functional replacement of the HIV-1 rev protein by the HTLV-1 rex protein. Rimsky, L., Hauber, J., Dukovich, M., Malim, M.H., Langlois, A., Cullen, B.R., Greene, W.C. Nature (1988) [Pubmed]
  2. A third-generation lentivirus vector with a conditional packaging system. Dull, T., Zufferey, R., Kelly, M., Mandel, R.J., Nguyen, M., Trono, D., Naldini, L. J. Virol. (1998) [Pubmed]
  3. Mutational definition of the human immunodeficiency virus type 1 Rev activation domain. Malim, M.H., McCarn, D.F., Tiley, L.S., Cullen, B.R. J. Virol. (1991) [Pubmed]
  4. The HIV-1 Rev activation domain is a nuclear export signal that accesses an export pathway used by specific cellular RNAs. Fischer, U., Huber, J., Boelens, W.C., Mattaj, I.W., Lührmann, R. Cell (1995) [Pubmed]
  5. Identification of a novel nuclear pore-associated protein as a functional target of the HIV-1 Rev protein in yeast. Stutz, F., Neville, M., Rosbash, M. Cell (1995) [Pubmed]
  6. RNA recognition by an isolated alpha helix. Tan, R., Chen, L., Buettner, J.A., Hudson, D., Frankel, A.D. Cell (1993) [Pubmed]
  7. Rev-dependent association of the intron-containing HIV-1 gag mRNA with the nuclear actin bundles and the inhibition of its nucleocytoplasmic transport by latrunculin-B. Kimura, T., Hashimoto, I., Yamamoto, A., Nishikawa, M., Fujisawa, J.I. Genes Cells (2000) [Pubmed]
  8. PRMT6 diminishes HIV-1 Rev binding to and export of viral RNA. Invernizzi, C.F., Xie, B., Richard, S., Wainberg, M.A. Retrovirology (2006) [Pubmed]
  9. The strength of the HIV-1 3' splice sites affects Rev function. Kammler, S., Otte, M., Hauber, I., Kjems, J., Hauber, J., Schaal, H. Retrovirology (2006) [Pubmed]
  10. Functional analysis of the interaction of the human immunodeficiency virus type 1 Rev nuclear export signal with its cofactors. Kiss, A., Li, L., Gettemeier, T., Venkatesh, L.K. Virology (2003) [Pubmed]
  11. Interaction of eukaryotic initiation factor 5A with the human immunodeficiency virus type 1 Rev response element RNA and U6 snRNA requires deoxyhypusine or hypusine modification. Liu, Y.P., Nemeroff, M., Yan, Y.P., Chen, K.Y. Biol. Signals (1997) [Pubmed]
  12. Development of an Rev-independent, minimal simian immunodeficiency virus-derived vector system. Pandya, S., Boris-Lawrie, K., Leung, N.J., Akkina, R., Planelles, V. Hum. Gene Ther. (2001) [Pubmed]
  13. Analysis of rev gene function on human immunodeficiency virus type 1 replication in lymphoid cells by using a quantitative polymerase chain reaction method. Arrigo, S.J., Weitsman, S., Rosenblatt, J.D., Chen, I.S. J. Virol. (1989) [Pubmed]
  14. Persistence of attenuated rev genes in a human immunodeficiency virus type 1-infected asymptomatic individual. Iversen, A.K., Shpaer, E.G., Rodrigo, A.G., Hirsch, M.S., Walker, B.D., Sheppard, H.W., Merigan, T.C., Mullins, J.I. J. Virol. (1995) [Pubmed]
  15. HIV-1 Genes vpr and nef Synergistically Damage Podocytes, Leading to Glomerulosclerosis. Zuo, Y., Matsusaka, T., Zhong, J., Ma, J., Ma, L.J., Hanna, Z., Jolicoeur, P., Fogo, A.B., Ichikawa, I. J. Am. Soc. Nephrol. (2006) [Pubmed]
  16. Diminished rev-mediated stimulation of human immunodeficiency virus type 1 protein synthesis is a hallmark of human astrocytes. Ludwig, E., Silberstein, F.C., van Empel, J., Erfle, V., Neumann, M., Brack-Werner, R. J. Virol. (1999) [Pubmed]
  17. Recognition of prominent viral epitopes induced by immunization with human immunodeficiency virus type 1 regulatory genes. Hinkula, J., Svanholm, C., Schwartz, S., Lundholm, P., Brytting, M., Engström, G., Benthin, R., Glaser, H., Sutter, G., Kohleisen, B., Erfle, V., Okuda, K., Wigzell, H., Wahren, B. J. Virol. (1997) [Pubmed]
  18. Rev inhibition strongly affects intracellular distribution of human immunodeficiency virus type 1 RNAs. Cmarko, D., Bøe, S.O., Scassellati, C., Szilvay, A.M., Davanger, S., Fu, X.D., Haukenes, G., Kalland, K.H., Fakan, S. J. Virol. (2002) [Pubmed]
  19. Overlapping cis sites used for splicing of HIV-1 env/nef and rev mRNAs. Swanson, A.K., Stoltzfus, C.M. J. Biol. Chem. (1998) [Pubmed]
  20. Infection of cynomolgus monkeys with a chimeric HIV-1/SIVmac virus that expresses the HIV-1 envelope glycoproteins. Li, J., Lord, C.I., Haseltine, W., Letvin, N.L., Sodroski, J. J. Acquir. Immune Defic. Syndr. (1992) [Pubmed]
  21. Role of polyadenylation in nucleocytoplasmic transport of mRNA. Huang, Y., Carmichael, G.C. Mol. Cell. Biol. (1996) [Pubmed]
  22. The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA. Malim, M.H., Hauber, J., Le, S.Y., Maizel, J.V., Cullen, B.R. Nature (1989) [Pubmed]
  23. The VP16 transcription activation domain is functional when targeted to a promoter-proximal RNA sequence. Tiley, L.S., Madore, S.J., Malim, M.H., Cullen, B.R. Genes Dev. (1992) [Pubmed]
  24. Feedback regulation of human immunodeficiency virus type 1 expression by the Rev protein. Felber, B.K., Drysdale, C.M., Pavlakis, G.N. J. Virol. (1990) [Pubmed]
  25. Codon optimization of the HIV-1 vpu and vif genes stabilizes their mRNA and allows for highly efficient Rev-independent expression. Nguyen, K.L., llano, M., Akari, H., Miyagi, E., Poeschla, E.M., Strebel, K., Bour, S. Virology (2004) [Pubmed]
  26. Retrovirus vector-mediated transfer of functional HIV-1 regulatory genes. Garcia, J.V., Miller, A.D. AIDS Res. Hum. Retroviruses (1994) [Pubmed]
  27. Regulation of HIV-1 env mRNA translation by Rev protein. Perales, C., Carrasco, L., González, M.E. Biochim. Biophys. Acta (2005) [Pubmed]
  28. Molecular biology of the human immunodeficiency virus type 1. Haseltine, W.A. FASEB J. (1991) [Pubmed]
  29. The development and testing of retroviral vectors expressing trans-dominant mutants of HIV-1 proteins to confer anti-HIV-1 resistance. Liem, S.E., Ramezani, A., Li, X., Joshi, S. Hum. Gene Ther. (1993) [Pubmed]
  30. Evaluation in rhesus macaques of Tat and rev-targeted immunization as a preventive vaccine against mucosal challenge with SHIV-BX08. Verrier, B., Le Grand, R., Ataman-Onal, Y., Terrat, C., Guillon, C., Durand, P.Y., Hurtrel, B., Aubertin, A.M., Sutter, G., Erfle, V., Girard, M. DNA Cell Biol. (2002) [Pubmed]
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