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Gene Review

tat  -  tat

Simian-Human immunodeficiency virus

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Disease relevance of tat

  • These viruses were composed of simian immunodeficiency virus SIVmac239 expressing HIV-1 env and the associated auxiliary HIV-1 genes tat, vpu, and rep [1].
  • HIV mRNA was detected as long as 91 days after inoculation of human cells and virus and the presence of HIV gag, nef, and tat/rev mRNA in HIV-infected SCID brains indicates ongoing HIV mRNA synthesis [2].
  • There is a direct correlation between the ability of tat to bind to TAR RNA and to activate HIV transcription [3].
  • In the brain, tat induces neuronal dysfunction/toxicity, even though neurons cannot be directly infected with HIV, resulting in CNS pathology, such as the dementia and encephalitis associated with NeuroAIDS [4].
 

Psychiatry related information on tat

  • In this study, we tested for antibody reactivities against gp120 and gp41-derived peptides, recombinant gp160, gp41 and tat in HIV-positive sera under antiretroviral therapy (ART) and determined their neutralization capacity [5].
 

High impact information on tat

  • In contrast, mutations that alter the sequence of the six nucleotide long loop at the tip of TAR RNA structure, and mutations which alter the sequence of the stem whilst preserving Watson-Crick base pairing, do not affect tat binding significantly [3].
  • The HIV-1 trans-activator protein, tat, is an RNA binding protein with a high affinity for a U-rich bulge near the tip of the stem in the RNA stem-loop structure encoded by the trans-activation responsive region (TAR) [3].
  • Introduction of a point mutation expected to destabilize base pairing in nearby residues of the TAR stem-loop structure reduced tat binding 10-fold [3].
  • The antitat gene expresses an antiviral RNA encoding polymeric Tat activation response elements in combination with an antisense tat moiety under the control of the HIV-1 long terminal repeat [6].
  • CEMx174- and C8166-45-based cell lines which contain a secreted alkaline phosphatase (SEAP) reporter gene under the control of a tat-responsive promoter derived from either SIVmac239 or HIV-1(NL4-3) were constructed [7].
 

Chemical compound and disease context of tat

  • However, the progesterone-mediated suppession of tat activation was not affected by mutation of the three consensus progesterone/androgen/glucocorticoid response elements within the HIV-1 LTR, previously shown by our group to be involved in glucocorticoid-mediated suppression of LTR-driven transcription [8].
 

Biological context of tat

  • Basal levels of SEAP activity from these cell lines were low but were greatly stimulated upon transfection of tat expression plasmids [7].
  • In the absence of tat, modification of the R region had only minor effects on cytoplasmic RNA stability, steady-state levels of vector RNA and packaging, consistent with the known primary function of R during reverse transcription [9].
  • In addition, PMA enhancement of an HIV-LTR driven reporter gene was not blocked by H7 in the presence or absence of exogenous tat, at concentrations capable of inhibiting upregulation of virus at the cellular level [10].
  • HIV tat is the transactivator of HIV-1, supporting efficient viral replication by stabilizing the transcription of viral genes [4].
 

Anatomical context of tat

  • We show that a tat-ovalbumin conjugate (tatOVA) can be delivered into cells and that subsequent processing and presentation occurs, resulting in effective and specific killing of these target cells by an OVA specific cytotoxic T-lymphocyte (CTL) line [11].
 

Associations of tat with chemical compounds

 

Analytical, diagnostic and therapeutic context of tat

  • Thus, the CpG-rich tat DNA vaccine may represent a promising candidate for preventive and therapeutic vaccination against AIDS [12].
  • These data indicate that in parallel to the decrease in viral load and antibodies against gp120, the neutralization capacity of sera under ART is reduced, and can not be compensated by an increase in tat-specific antibodies [5].

References

  1. An env gene derived from a primary human immunodeficiency virus type 1 isolate confers high in vivo replicative capacity to a chimeric simian/human immunodeficiency virus in rhesus monkeys. Reimann, K.A., Li, J.T., Voss, G., Lekutis, C., Tenner-Racz, K., Racz, P., Lin, W., Montefiori, D.C., Lee-Parritz, D.E., Lu, Y., Collman, R.G., Sodroski, J., Letvin, N.L. J. Virol. (1996) [Pubmed]
  2. Potential relationships between the presence of HIV, macrophages, and astrogliosis in SCID mice with HIV encephalitis. Avgeropoulos, N.G., Burris, G.W., Ohlandt, G.W., Wesselingh, S.L., Markham, R.B., Tyor, W.R. Journal of neuro-AIDS. (1998) [Pubmed]
  3. HIV-1 tat protein stimulates transcription by binding to a U-rich bulge in the stem of the TAR RNA structure. Dingwall, C., Ernberg, I., Gait, M.J., Green, S.M., Heaphy, S., Karn, J., Lowe, A.D., Singh, M., Skinner, M.A. EMBO J. (1990) [Pubmed]
  4. HIV tat and neurotoxicity. King, J.E., Eugenin, E.A., Buckner, C.M., Berman, J.W. Microbes Infect. (2006) [Pubmed]
  5. Changes in HIV-specific antibody responses and neutralization titers in patients under ART. Falkensammer, B., Freissmuth, D., H??bner, L., Speth, C., Dierich, M.P., Stoiber, H. Front. Biosci. (2007) [Pubmed]
  6. Transduction of CD34+ hematopoietic progenitor cells with an antitat gene protects T-cell and macrophage progeny from AIDS virus infection. Rosenzweig, M., Marks, D.F., Hempel, D., Lisziewicz, J., Johnson, R.P. J. Virol. (1997) [Pubmed]
  7. Neutralization sensitivity of cell culture-passaged simian immunodeficiency virus. Means, R.E., Greenough, T., Desrosiers, R.C. J. Virol. (1997) [Pubmed]
  8. Interaction of pregnancy steroid hormones and zidovudine in inhibition of HIV type 1 replication in monocytoid and placental Hofbauer cells: implications for the prevention of maternal-fetal transmission of HIV. Lee, A.W., Mitra, D., Laurence, J. AIDS Res. Hum. Retroviruses (1997) [Pubmed]
  9. Functional replacement of the R region of simian immunodeficiency virus-based vectors by heterologous elements. Brandt, S., Grunwald, T., Lucke, S., Stang, A., Uberla, K. J. Gen. Virol. (2006) [Pubmed]
  10. Phorbol ester-mediated induction of HIV-1 from a chronically infected promonocyte clone: blockade by protein kinase inhibitors and relationship to tat-directed trans-activation. Laurence, J., Sikder, S.K., Jhaveri, S., Salmon, J.E. Biochem. Biophys. Res. Commun. (1990) [Pubmed]
  11. Tat-mediated protein delivery can facilitate MHC class I presentation of antigens. Moy, P., Daikh, Y., Pepinsky, B., Thomas, D., Fawell, S., Barsoum, J. Mol. Biotechnol. (1996) [Pubmed]
  12. Vaccination with DNA containing tat coding sequences and unmethylated CpG motifs protects cynomolgus monkeys upon infection with simian/human immunodeficiency virus (SHIV89.6P). Cafaro, A., Titti, F., Fracasso, C., Maggiorella, M.T., Baroncelli, S., Caputo, A., Goletti, D., Borsetti, A., Pace, M., Fanales-Belasio, E., Ridolfi, B., Negri, D.R., Sernicola, L., Belli, R., Corrias, F., Macchia, I., Leone, P., Michelini, Z., ten Haaft, P., Buttò, S., Verani, P., Ensoli, B. Vaccine (2001) [Pubmed]
 
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