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Gene Review

rex  -  p27

Human T-lymphotropic virus 1

 
 
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Disease relevance of rex

 

High impact information on rex

  • Transfection of the HIV-infected murine cells with a HTLV-1 rex-expressing vector failed to rescue the rev- phenotype, indicating that the block extended to rex function [6].
  • To localize differences involved in the ability of the clones to cause infection, six chimeric HTLV-I clones were constructed by shuffling corresponding fragments containing the substitutions in the LTRs, the gag/pol region and the rex region between K30p and K34p [7].
  • Homologies at the nucleotide sequence level of PTLV-L, prototype simian T-lymphotropic virus-PH969, with HTLV-I and -II, respectively, were 62% and 64% overall, 65% and 70% in the env region, and 80% and 80% in the partial tax/rex sequence [8].
  • In a cDNA library a 1802-bp-long fragment was identified that extends from the env region, including the complete transmembrane protein gene, to part of the tax/rex gene [8].
  • The role of the X region of the genome of the human T-cell leukemia virus type I (HTLV-I) in the immortalization of lymphocytes has been difficult to distinguish from its role in viral replication as this region encodes at least two genes, tax and rex, required for replication and the expression of viral proteins [9].
 

Chemical compound and disease context of rex

  • Our results indicate that p24rex of HTLV-II is not initiated at an internal AUG and that the internal methionine codons are not crucial to the function of the rex gene and, ultimately, the transforming properties of the virus [10].
  • A selectable retrovirus vector based on a full length HTLV-1 provirus clone, pCS-HTLV-1, was constructed by replacing the coding regions for tax, rex and the 3' region of env with the prokaryotic neomycin resistance gene under the control of the CMV promoter [11].
 

Biological context of rex

 

Anatomical context of rex

  • The N-terminal 19 amino acids of rex-encoded protein (Rex) has been shown to be sufficient to direct hybrid proteins to the cell nucleolus [13].
  • Furthermore, tax/rex mRNA was detected by RT-PCR in the PBMCs of two monkeys 8 to 12 days after inoculation and in the spleens and lymph nodes of the monkey sacrificed on day 12 [16].
  • Here we generated and characterized a unique proviral clone (H1IT) in which the tax and rex genes were separated by expressing Tax from an internal ribosome entry site [17].
  • In this animal, scattered HTLV-1 tax/rex mRNA-positive lymphocytes were detected by in situ hybridization in frozen sections of the spleen, around the germinal centers and close to the arterial capillaries [16].
  • In chronically infected cell lines, the pX-tax/rex mRNA was present at 500- to 2500-fold higher levels than the pX-tax-orfII mRNA and at approximately 1000-fold higher levels than pX-rex-orfI mRNA [18].
 

Associations of rex with chemical compounds

  • The internal methionine codons of human T-cell leukemia virus type II rex gene are not required for p24rex production or virus replication and transformation [10].
  • The analysis of levels and distribution patterns of the unspliced env and of the singly spliced tax/rex transcripts suggests that the failure in envelope glycoprotein synthesis may be ascribed to a deficiency of Rex in mediating the nucleocytoplasmic transport of unspliced env RNAs in these cells [19].
 

Analytical, diagnostic and therapeutic context of rex

  • Sequence analysis of the 127-bp fragment amplified by the tax/rex primers from 4 of these individuals was found to be identical to that in prototypic HTLV-I [3].
  • To develop gene therapy for patients with human T cell leukemia virus type I (HTLV-I)-associated arthropathy (HAAP), we investigated the effects of ribozyme-mediated cleavage of HTLV-I tax/rex messenger RNA (mRNA) on synovial overgrowth [20].
  • Titration of cellular export factors, but not heteromultimerization, is the molecular mechanism of trans-dominant HTLV-1 rex mutants [21].
  • We used oligonucleotide-directed mutagenesis to generate a series of mutant HTLV-I rex genes [22].
  • Among 17 HTLV-I carriers, 1 person who was seronegative and 1 who was PCR-negative were identified. gag and tax/rex PCR titers correlated with each other (r = .92; P < .001) [23].

References

  1. Trans-dominant inactivation of HTLV-I and HIV-1 gene expression by mutation of the HTLV-I Rex transactivator. Rimsky, L., Dodon, M.D., Dixon, E.P., Greene, W.C. Nature (1989) [Pubmed]
  2. 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]
  3. Human T-cell leukemia virus type I tax/rex DNA and RNA in cutaneous T-cell lymphoma. Ghosh, S.K., Abrams, J.T., Terunuma, H., Vonderheid, E.C., DeFreitas, E. Blood (1994) [Pubmed]
  4. Human T-cell leukemia virus type I or a related retrovirus in patients with mycosis fungoides/Sézary syndrome and Kaposi's sarcoma. Srivastava, B.I., Banki, K., Perl, A. Cancer Res. (1992) [Pubmed]
  5. Efficient transfer of synthetic ribozymes into cells using hemagglutinating virus of Japan (HVJ)-cationic liposomes. Application for ribozymes that target human t-cell leukemia virus type I tax/rex mRNA. Kitajima, I., Hanyu, N., Soejima, Y., Hirano, R., Arahira, S., Yamaoka, S., Yamada, R., Maruyama, I., Kaneda, Y. J. Biol. Chem. (1997) [Pubmed]
  6. A human cell factor is essential for HIV-1 Rev action. Trono, D., Baltimore, D. EMBO J. (1990) [Pubmed]
  7. Infectivity of chimeric human T-cell leukemia virus type I molecular clones assessed by naked DNA inoculation. Zhao, T.M., Robinson, M.A., Bowers, F.S., Kindt, T.J. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  8. A primate T-lymphotropic virus, PTLV-L, different from human T-lymphotropic viruses types I and II, in a wild-caught baboon (Papio hamadryas). Goubau, P., Van Brussel, M., Vandamme, A.M., Liu, H.F., Desmyter, J. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  9. Transformation to continuous growth of primary human T lymphocytes by human T-cell leukemia virus type I X-region genes transduced by a Herpesvirus saimiri vector. Grassmann, R., Dengler, C., Müller-Fleckenstein, I., Fleckenstein, B., McGuire, K., Dokhelar, M.C., Sodroski, J.G., Haseltine, W.A. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  10. The internal methionine codons of human T-cell leukemia virus type II rex gene are not required for p24rex production or virus replication and transformation. Green, P.L., Xie, Y.M., Chen, I.S. J. Virol. (1990) [Pubmed]
  11. Detection of human T-cell leukaemia virus 1 permissive cells using cell lines producing selectable recombinant virions. Copeland, K.F., Haaksma, A.G., Derse, D., Heeney, J.L. J. Virol. Methods (1994) [Pubmed]
  12. Human T-cell lymphotropic virus type 3: complete nucleotide sequence and characterization of the human tax3 protein. Calattini, S., Chevalier, S.A., Duprez, R., Afonso, P., Froment, A., Gessain, A., Mahieux, R. J. Virol. (2006) [Pubmed]
  13. Nucleolar targeting signal of human T-cell leukemia virus type I rex-encoded protein is essential for cytoplasmic accumulation of unspliced viral mRNA. Nosaka, T., Siomi, H., Adachi, Y., Ishibashi, M., Kubota, S., Maki, M., Hatanaka, M. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  14. Mapping of multiple RNA binding sites of human T-cell lymphotropic virus type I rex protein within 5'- and 3'-Rex response elements. Askjaer, P., Kjems, J. J. Biol. Chem. (1998) [Pubmed]
  15. Tenosynovial nodulosis in a patient infected with human T cell lymphotropic virus I. Hasunuma, T., Morimoto, T., Tran, T.M., Müller-Ladner, U., Aono, H., Ogawa, R., Gay, S., Nishioka, K. Arthritis Rheum. (1997) [Pubmed]
  16. Lymphoid organs as a major reservoir for human T-cell leukemia virus type 1 in experimentally infected squirrel monkeys (Saimiri sciureus): provirus expression, persistence, and humoral and cellular immune responses. Kazanji, M., Ureta-Vidal, A., Ozden, S., Tangy, F., de Thoisy, B., Fiette, L., Talarmin, A., Gessain, A., de Thé, G. J. Virol. (2000) [Pubmed]
  17. Human T-cell leukemia virus type 1 expressing nonoverlapping tax and rex genes replicates and immortalizes primary human T lymphocytes but fails to replicate and persist in vivo. Younis, I., Yamamoto, B., Phipps, A., Green, P.L. J. Virol. (2005) [Pubmed]
  18. Roles of viral and cellular proteins in the expression of alternatively spliced HTLV-1 pX mRNAs. Princler, G.L., Julias, J.G., Hughes, S.H., Derse, D. Virology (2003) [Pubmed]
  19. The human T-cell leukemia virus type 1 Rex regulatory protein exhibits an impaired functionality in human lymphoblastoid Jurkat T cells. Hamaia, S., Cassé, H., Gazzolo, L., Duc Dodon, M. J. Virol. (1997) [Pubmed]
  20. Ribozyme-based gene cleavage approach to chronic arthritis associated with human T cell leukemia virus type I: induction of apoptosis in synoviocytes by ablation of HTLV-I tax protein. Kitajima, I., Hanyu, N., Kawahara, K., Soejima, Y., Kubo, T., Yamada, R., Kaneda, Y., Maruyama, I. Arthritis Rheum. (1997) [Pubmed]
  21. Titration of cellular export factors, but not heteromultimerization, is the molecular mechanism of trans-dominant HTLV-1 rex mutants. Heger, P., Rosorius, O., Hauber, J., Stauber, R.H. Oncogene (1999) [Pubmed]
  22. Transdominant repressors for human T-cell leukemia virus type I rex and human immunodeficiency virus type 1 rev function. Böhnlein, S., Pirker, F.P., Hofer, L., Zimmermann, K., Bachmayer, H., Böhnlein, E., Hauber, J. J. Virol. (1991) [Pubmed]
  23. Dependency of antibody titer on provirus load in human T lymphotropic virus type I carriers: an interpretation for the minor population of seronegative carriers. Miyata, H., Kamahora, T., Iha, S., Katamine, S., Miyamoto, T., Hino, S. J. Infect. Dis. (1995) [Pubmed]
 
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