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At least 937 records · Page 52Linked to original sources
PubMed2000

Attachment of human immunodeficiency virus-1 (HIV-1) particles bearing host-encoded B7-2 proteins leads to nuclear factor-kappa B- and nuclear factor of activated T cells-dependent activation of HIV-1 long terminal repeat transcription.

Previous studies have shown that human immunodeficiency virus type-1 (HIV-1) can incorporate several surface proteins of host origin. Recent findings indicate that host-encoded cell surface constituents retain their functionality when found embedded into the viral envelope. The primary objective of the current study was to define whether interaction between some specific virion-bound host proteins with their natural cognate ligands present on target cells could mediate intracellular signaling cascade(s). For this purpose, we have generated a whole series of isogenic virus stocks (NL4-3 backbone) bearing or not bearing on their surface foreign CD28, CD54 (ICAM-1), CD80 (B7-1) or CD86 (B7-2) proteins. Our results indicate that incubation of human T lymphoid cells with virions bearing host-derived B7-2 proteins and anti-CD3 antibody can potently activate HIV-1 long terminal repeat-driven gene expression. This up-regulating effect necessitates the involvement of nuclear factor-kappa B (NF-kappa B) and nuclear factor of activated T cells (NFAT) as revealed by the use of vectors coding for dominant negative versions of both transcription factors (i.e. I kappa B alpha S32A/36A and dnNFAT) and band shift assays. The increase of NF-kappa B activity was abolished when infection with B7-2-bearing HIV-1 particles was performed in the presence of the fusion protein CTLA-4 Ig suggesting that the interaction between virally embedded B7-2 and CD28 on the target cell is responsible for the observed NF-kappa B induction. The findings presented here provide the first demonstration that host-encoded proteins acquired by HIV-1 can mediate signal transduction events.

Antigens, CD↗
PubMed1985

Hormonal response region in the mouse mammary tumor virus long terminal repeat can be dissociated from the proviral promoter and has enhancer properties.

The proviral DNA of mouse mammary tumor virus (MMTV) contains a regulatory region closely associated with its promoter, which subjects transcription to the control of glucocorticoid hormones. Delimitation analysis of a chimeric MMTV long terminal repeat-thymidine kinase gene (LTR-tk) has shown that the hormonal regulation sequence is confined to 202 nucleotides preceding the LTR-specific RNA initiation site. A second RNA initiation site (tk-specific mRNA) placed close to the regulatory MMTV sequence by in vitro recombination is also subjected to hormonal stimulation in transfected cells. A series of plasmids with deletions around the LTR cap site progressing from 3' to 5' was made and functionally tested. In vitro deletion of MMTV LTR sequences comprising the RNA initiation sequence and the "TATA" box do not effect hormonal regulation at the tk-specific mRNA start site. Nucleotides up to position -59 from the LTR initiation site could be deleted without influence on the glucocorticoid regulation, whereas deletions to position -65 abolished the hormonal effect on the tk gene transcription. A short MMTV LTR segment containing nucleotides -236 to -52 from the LTR initiation site was recombined with the tk gene or the alpha-globin gene. This fragment confers hormonal inducibility onto the heterologous genes over distances of 0.4 or 1.1 kilobases. The hormonal response region functions when it is placed either 5' or 3' of the regulated gene in both of the possible orientations and is reminiscent of an enhancer sequence.

Animals↗
PubMed1983

Nucleotide sequence analysis of the long terminal repeat of murine virus-like DNA (VL30) and its adjacent sequences: resemblance to retrovirus proviruses.

VL30 DNA represents a retrovirus-like multigene family of mice whose genetic origin is unknown. We have now determined the primary nucleotide sequences and the adjacent sequences of the long terminal direct repeats (LTRs) possessed by a randomly selected VL30 unit. The LTR of the VL30 unit comprised 435 nucleotide base pairs and had an inverted repeat of five bases at its 5' and 3' termini. At the joints with flanking mouse DNA was the VL30 sequence (5')TG . . . CA(3') and a tetranucleotide direct repeat of flanking sequences. At the inner boundary of the 5' LTR was an 18-base sequence that is complementary to tRNApro, and at the inner boundary of the 3' LTR was a purine-rich tract ending with AATG. These results suggested that VL30 DNA used the same integration strategy that is exercised by retrovirus proviruses and transposable elements and that the VL30 LTR is synthesized in a similar way that the LTR of retroviruses is synthesized. The data thus reinforce the retrovirus-like nature of VL30 genetic information.

Animals↗
PubMed1984

Structure of circular copies of the 412 transposable element present in Drosophila melanogaster tissue culture cells, and isolation of a free 412 long terminal repeat.

We have isolated, from Drosophila melanogaster tissue culture cells, extrachromosomal circular forms of the transposable element 412, and have cloned some of them in bacteriophage lambda. A total of 24 clones have been analysed in detail by restriction and heteroduplex mapping. Seventeen clones are virtually identical, and contain complete 412 elements with one copy of the long terminal direct repeat (LTR). The remaining seven clones are all different and contain various rearrangements. Four have deletions, two have some 412 sequence substituted by other DNA and one has both an inversion and a deletion. The clone containing the inversion has two LTRs in inverted orientation and separated by a few thousand bases of 412 DNA. The base sequences of the two LTRs in this clone, and of the LTR in one of the 17 clones containing complete elements are very similar to that of the 481 base-pair LTR of a genomic 412 element. We have found no evidence, in either cloned or uncloned material, for 412 elements with two LTRs as a tandem direct repeat. We have found that there are several "free" 412 LTRs in genomic DNA from D. melanogaster strains Canton S and Oregon R, and from D. melanogaster tissue culture cells. We have cloned and sequenced one of these free LTRs. It is 475 base-pairs long and is flanked by a direct repeat four base-pairs long. This sequence differs from that of the 481 base-pair repeat at 16 places including a ten base deletion.

Animals↗
PubMed1997

The long terminal repeats of human immunodeficiency virus type-1 and human T-cell leukemia virus type-I are activated by 12-O-tetradecanoylphorbol-13-acetate through different pathways.

The LTRs of HIV-1 and HTLV-I have been shown by several laboratories to be activated by 12-O-tetradecanoylphorbol-13-acetate (TPA). This agent is a potent activator of protein kinase C (PKC). However, long exposure to TPA downregulates PKC in many cell types. We demonstrated that TPA treatment of Jurkat cells for more than 24 hr resulted in a sever depletion of this enzyme. Therefore, to explore the role of PKC in the effect of TPA on these LTRs, we transfected Jurkat cells with HIV-1 LTR-CAT or HTLV-I LTR-CAT construct after 72 hr of TPA pretreatment. While this TPA pretreatment considerably reduced the HIV-1 LTR basal expression, it strongly stimulated the expression of HTLV-I LTR. Furthermore, when TPA was added after transfection, a strong stimulation of HIV-1 LTR was observed, which could be abrogated by PKC inhibitors like H7 and chelerythryn. However, under these conditions TPA stimulated HTLV-I LTR to a lesser extent than did the long-term TPA pretreatment. Moreover, this stimulation was enhanced by the PKC inhibitors. Thus our data indicate that while the effect of TPA on HIV-1 LTR is strictly dependent on PKC activity, its effect on HTLV-I LTR is exerted via a different pathway that not only does not require PKC activation but rather seems to be antagonized by the activated PKC. Using a deletion mutant of HTLV-I LTR we mapped the PKC-independent effect of TPA to the c-ets responsive region 1 (ERR-1) located in U3 of this LTR.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2004

Repression of the human immunodeficiency virus type-1 long terminal repeat by the c-Myc oncoprotein.

The effect of trans-acting factors on cis-acting DNA elements on the HIV-1 promoter are the principal determinant regulating transcriptional activation and repression. Host factors that limit viral replication can contribute to the emergence and maintenance of proviral reservoirs. The current paradigm is that this sub-population of latently infected cells confers a biological advantage to the virus by facilitating evasion of immunologic responses and therapeutic strategies resulting in life-long and persistent infection. In this report, we show that ectopic expression of the nuclear phosphoprotein, c-Myc can inhibit HIV-1 gene expression and virus production in CD4+ T-lymphocytes. The effect exerted does not appear to involve other known functions of c-Myc such as proliferation, or apoptosis. The mechanism does implicate c-Myc in a direct role. We have found evidence that c-Myc can specifically recognize the HIV-1 initiator element surrounding the start site of transcription and linker scanning mutagenesis experiments confirmed a loss of c-Myc-mediated repression in the absence of this region. Moreover, we show that c-Myc can interact with the initiator binding proteins YY-1 and LBP-1 and can cooperate with these factors to synergistically repress HIV-1 LTR transcription. Taken together, these results indicate that c-Myc is an important regulator of HIV-1 transcription that potentially contributes to the latent proviral state.

Apoptosis↗
PubMed2003

[Retroviral long terminal repeats: structure and function].

Characteristic genetic sequences, named as LTR, are present at the end of retroviral genomes. They are involved in the integration of viral nucleic acid into chromosomes of cell host. In addition, LTR modulates the transcription of retroviral genes and, in this form, determine their virulence. LTR from distinct HIV-1 subtypes show structural differences which may result in distinct biological behaviors and, ultimately, different disease progression.

Genome, Viral↗
PubMed1996

Murine leukemia virus-based Tat-inducible long terminal repeat replacement vectors: a new system for anti-human immunodeficiency virus gene therapy.

We have constructed new murine leukemia virus (MLV)-based vectors (TIN vectors) which, following integration, contain human immunodeficiency virus (HIV) type 1 U3 and R sequences in place of the MLV U3 and R regions. This provides, for the first time, single transcriptional unit retroviral vectors under the control of Tat. TIN vectors have several advantages for anti-HIV gene therapy applications.

3T3 Cells↗
PubMed1998

An interferon regulatory factor binding site in the U5 region of the bovine leukemia virus long terminal repeat stimulates Tax-independent gene expression.

Bovine leukemia virus (BLV) replication is controlled by both cis- and trans-acting elements. The virus-encoded transactivator, Tax, is necessary for efficient transcription from the BLV promoter, although it is not present during the early stages of infection. Therefore, sequences that control Tax-independent transcription must play an important role in the initiation of viral gene expression. This study demonstrates that the R-U5 sequence of BLV stimulates Tax-independent reporter gene expression directed by the BLV promoter. R-U5 was also stimulatory when inserted immediately downstream from the transcription initiation site of a heterologous promoter. Progressive deletion analysis of this region revealed that a 46-bp element corresponding to the 5' half of U5 is principally responsible for the stimulation. This element exhibited enhancer activity when inserted upstream or downstream from the herpes simplex virus thymidine kinase promoter. This enhancer contains a binding site for the interferon regulatory factors IRF-1 and IRF-2. A 3-bp mutation that destroys the IRF recognition site caused a twofold decrease in Tax-independent BLV long terminal repeat-driven gene expression. These observations suggest that the IRF binding site in the U5 region of BLV plays a role in the initiation of virus replication.

Animals↗
PubMed2001

Two long terminal repeat circles and persistent HIV-1 replication.

Building on the success of combination antiretroviral drug therapy will require a better understanding of the underlying basis for viral persistence. Characterization of the therapeutic, viral, and immunological factors that influence the size and stability of viral reservoirs will foster the development of strategies to control or eliminate HIV-1 from infected individuals. Here we review recent work aimed at delineating the complex interplay between viral replication, the immune system, and viral reservoirs. Finally, we address the implications and clinical significance of the residual replication that persists in infected individuals on potent antiretroviral therapy to evaluate both the possible risks and benefits of ongoing HIV-1 replication.

CD4-Positive T-Lymphocytes↗