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Review
. 2017 Apr 18;8(16):27569-27581.
doi: 10.18632/oncotarget.15174.

VSports注册入口 - Tat is a multifunctional viral protein that modulates cellular gene expression and functions

Evan Clark  1 , Brenda Nava  1 , Massimo Caputi  1
Affiliations
Review

Tat is a multifunctional viral protein that modulates cellular gene expression and functions

Evan Clark et al. Oncotarget. .

Abstract

The human immunodeficiency virus type I (HIV-1) has developed several strategies to condition the host environment to promote viral replication and spread. Viral proteins have evolved to perform multiple functions, aiding in the replication of the viral genome and modulating the cellular response to the infection. Tat is a small, versatile, viral protein that controls transcription of the HIV genome, regulates cellular gene expression and generates a permissive environment for viral replication by altering the immune response and facilitating viral spread to multiple tissues VSports手机版. Studies carried out utilizing biochemical, cellular, and genomic approaches show that the expression and activity of hundreds of genes and multiple molecular networks are modulated by Tat via multiple mechanisms. .

Keywords: HIV-1; Tat; gene regulation; transcription V体育安卓版. .

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Conflict of interest statement

CONFLICTS OF INTEREST

There authors declare that there is no conflict of interest.

Figures (V体育ios版)

Figure 1
Figure 1. Diagram of the functional domains of HIV-1 Tat
Tat is subdivided into six functional domains. The first 5 domains, coded by the first exon, are sufficient for trans-activation of viral transcription and modulate most of the interactions with Tat cellular partners. The arginine rich basic domain functions as a RNA binding domain (RBD), a protein transduction domain (PTD) and nuclear localization signal (NLS). The second exon codes for the C-terminal domain that, which contains a tripeptide RGD motif, does not appear to be required for Tat functions in cell culture but might contribute to viral pathogenesis in-vivo.
Figure 2
Figure 2. Tat activates viral transcription
A. In the early stage of viral infection, in the absence of Tat, transcription is limited by a pausing complex (NELF, DSIF) that assembles onto the nascent transcript. P-TEFb is sequestered in multiple complexes. B. During the later stages of the viral infection Tat is present at high concentrations and induces relocation of P-TEFb from diverse nucleoplasmic complexes to the nascent transcript within the paused RNAPII complex by its binding to TAR. This triggers activation of the P-TEFb kinase and hyper-phosphorylation of the RNAPII CTD and the NELF/DSIF complex.
Figure 3
Figure 3. Tat contributes to the disruption of the blood brain barrier, neuroinflammation and neurotoxicity
Extracellular Tat can passively cross the BBB decreasing the expression of tight junctions proteins and inducing the expression of factors that promote the disruption of the BBB. After crossing the BBB Tat is efficiently taken up by multiple cells, including neurons and astrocytes, this results in the release of several soluble factors that promote neuroinflammation and function as monocyte chemoattractant facilitating the invasion of the CNS by infected monocytes and macrophages. Tat directly induces neuronal toxicity by modulating the expression of miRNAs, disrupting endolysosomes functions, promoting oxidative damage and inpairing the functions of the glutamatergic neurotransmission system. Tat can also promote the remaval of anti retro viral drugs from the CNS by upregulating the P-glycoprotein (P-gp) pump.
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References

    1. Viglianti GA, Mullins JI. Functional comparison of transactivation by simian immunodeficiency virus from rhesus macaques and human immunodeficiency virus type 1. Journal of virology. 1988;62:4523–4532. - PMC - PubMed
    1. Verhoef K, Bauer M, Meyerhans A, Berkhout B. On the role of the second coding exon of the HIV-1 Tat protein in virus replication and MHC class I downregulation. AIDS research and human retroviruses. 1998;14:1553–1559. - V体育ios版 - PubMed
    1. Howcroft TK, Strebel K, Martin MA, Singer DS. Repression of MHC class I gene promoter activity by two-exon Tat of HIV. Science (New York, N.Y.) 1993;260:1320–1322. - "VSports手机版" PubMed
    1. Puglisi JD, Chen L, Blanchard S, Frankel AD. Solution structure of a bovine immunodeficiency virus Tat-TAR peptide-RNA complex. Science New York, N.Y. 1995;270:1200–1203. - PubMed
    1. Tahirov TH, Babayeva ND, Varzavand K, Cooper JJ, Sedore SC, Price DH. Crystal structure of HIV-1 Tat complexed with human P-TEFb. Nature. 2010;465:747–751. - PMC - PubMed

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