Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Jembrana disease virus (JDV) is a newly identified bovine lentivirus that is closely related to the bovine immunodeficiency virus (BIV). JDV contains a tat gene, encoded by two exons, which has potent transactivation activity. Cotransfection of the JDV tat expression plasmid with the JDV promoter chloramphenicol acetyltransferase (CAT) construct pJDV-U3R resulted in a substantial increase in the level of CAT mRNA transcribed from the JDV long terminal repeat (LTR) and a dramatic increase in the CAT protein level. Deletion analysis of the LTR sequences showed that sequences spanning nucleotides -68 to +53, including the TATA box and the predicted first stem-loop structure of the predicted Tat response element (TAR), were required for efficient transactivation. The results, derived from site-directed mutagenesis experiments, suggested that the base pairing in the stem of the first stem-loop structure in the TAR region was important for JDV Tat-mediated transactivation; in contrast, nucleotide substitutions in the loop region of JDV TAR had less effect. For the JDV LTR, upstream sequences, from nucleotide -196 and beyond, as well as the predicted secondary structures in the R region, may have a negative effect on basal JDV promoter activity. Deletion of these regions resulted in a four- to fivefold increase in basal expression. The JDV Tat is also a potent transactivator of other animal and primate lentivirus promoters. It transactivated BIV and human immunodeficiency virus type 1 (HIV-1) LTRs to levels similar to those with their homologous Tat proteins. In contrast, HIV-1 Tat has minimal effects on JDV LTR expression, whereas BIV Tat moderately transactivated the JDV LTR. Our study suggests that JDV may use a mechanism of transactivation similar but not identical to those of other animal and primate lentiviruses.
 ...
PMID:Characterization of the Jembrana disease virus tat gene and the cis- and trans-regulatory elements in its long terminal repeats. 984 71

Fusions of the human immunodeficiency virus type 1 (HIV-1) transactivator protein Tat to the green fluorescent protein (GFP) were used to study the intracellular localization, trafficking, and interactions of Tat in human cells. Tagging Tat with GFP did not change its nuclear localization or ability to act as a transactivator. Tat-GFP expressed at low levels was found in the nucleus, whereas overexpression resulted in nucleolar accumulation. A Tat-GFP hybrid protein containing in addition the HIV-1 Rev nuclear export signal (NES) localized predominantly to the cytoplasm. This shuttle protein, Tat-GFP-NES, transactivated the HIV-1 long terminal repeat. Thus a Tat molecule being only transiently present in the nucleus is active and nucleolar accumulation of Tat is not prerequisite for function. A coexpression assay previously used to define protein interaction domains in the HIV-1 Rev protein [R. H. Stauber, E. Afonina, S. Gulnik, J. Erickson, and G. N. Pavlakis (1998a). Virology 251, 38-48.] indicated that Tat exists predominantly as a monomer and does not form stable multimers with B23 in living cells. Using a heterokaryon fusion assay, we found that Tat-GFP was able to shuttle between the nucleus and the cytoplasm. Tat therefore has the potential to perform functions in the nucleus as well as in the cytoplasm.
 ...
PMID:Intracellular trafficking and interactions of the HIV-1 Tat protein. 987 23

The transcriptional transactivator Tat from HIV binds to the transactivation response element (TAR) RNA to increase rates of elongation of viral transcription. Human cyclin T supports these interactions between Tat and TAR. In this study, we report the sequence of mouse cyclin T and identify the residues from positions 1 to 281 in human cyclin T that bind to Tat and TAR. Mouse cyclin T binds to Tat weakly and is unable to facilitate interactions between Tat and TAR. Reciprocal exchanges of the cysteine and tyrosine at position 261 in human and mouse cyclin T proteins also render human cyclin T inactive and mouse cyclin T active. These findings reveal the molecular basis for the restriction of Tat transactivation in rodent cells.
 ...
PMID:Interactions between human cyclin T, Tat, and the transactivation response element (TAR) are disrupted by a cysteine to tyrosine substitution found in mouse cyclin T. 999 16

The MHC class I complex, which binds and presents peptide antigen, is composed of a class I heavy chain and the beta2-microglobulin light chain. HIV-1, which induces a profound immunodeficiency in infected individuals, encodes proteins that cause decreased expression of class I heavy chain. We now report that the HIV Tat protein, which is a potent transactivator of viral transcription, is also a potent repressor of the beta2-microglobulin gene. Repression is mediated through the basal promoter of the beta2-microglobulin gene, which is shown to be predominantly regulated by an initiator element. Tat repression is further augmented by the short viral transcript, TAR, which interacts with Tat. Tat-mediated repression of beta2-microglobulin expression, together with its known repression of class I gene transcription, provides an effective mechanism by which HIV could prevent cell surface expression of the MHC class I complex and avoid immune surveillance.
 ...
PMID:HIV Tat represses transcription of the beta 2-microglobulin promoter. 1019 91

The ZFX gene is ubiquitously transcribed and highly conserved among vertebrates. The integrity of Zfx, its murine homologue, has been shown to be important for growth during embryogenesis and sustained gamete production. Alternative splicing was shown to result in production of mRNAs coding for either ZFX804or a shorter isoform initiated downstream, ZFX575. ZFX575was previously shown to be a potent transactivator of the HLA-A11 promoter. Here, the HIV-1 LTR is also shown to be potently transactivated by ZFX575in several cell types, while ZFX804activity is found to be similar to that of ZFX575, null or intermediary according to the cell type. In all cell types, the HIV-1 TATA box sequence is a key element of transactivation, while the Sp1 or NFkappaB sites are variably required, according to the cell type. Overall, the results suggest that ZFX575and ZFX804could play a role in HIV-1 LTR induction as co-activators enhancing productive interactions between upstream transactivators and the basal transcription complexes recruited by the TATA box.
 ...
PMID:ZFX transactivation of the HIV-1 LTR is cell specific and depends on core enhancer and TATA box sequences. 1021 88

To study the role in AIDS pathogenesis of the human immunodeficiency virus type 1 (HIV-1) Tat protein, a transactivator of viral and cellular genes, we generated transgenic mice with a recombinant DNA containing BK virus (BKV) early region and the HIV-1 tat gene, directed by its own promoter-enhancer. DNA hybridization revealed that the transgene is stably maintained in all organs of transgenic mice as a tandem insertion in a number of copies ranging from 5 to 20 per cell. In addition, tat and BKV RNA were expressed in all tissues. Transgenic mice developed three types of lesions: 1) tumors, 2) hyperplastic and dysplastic lesions, and 3) non-neoplastic lesions. Tumors of different histotypes, such as lymphomas, adenocarcinomas of skin glands, leiomyosarcomas, skin squamous cell carcinomas, hepatomas, hepatocarcinomas, and cavernous liver hemangiomas, developed in 29% of transgenic animals. The majority of tumors were malignant, invasive, and producing metastases. Conversely, tumors of only two histotypes (lymphomas and adenocarcinomas of skin glands) appeared in control mice. Hyperplastic and dysplastic lesions were more frequent in transgenic than in control mice and involved the skin or its adnexes, the liver and the rectum, indicating multiple targets for the activity of the transgene. Pyelonephritis, frequently complicated with hydronephrosis, inflammatory eye lesions, and amyloid depositions represented the most frequent non-neoplastic lesions detected in transgenic mice. Many of the pathological findings observed in this animal model are comparable to similar lesions appearing in AIDS patients, suggesting a relevant role for Tat in the pathogenesis of such lesions during the course of AIDS.
 ...
PMID:Morphological, histochemical, immunohistochemical, and ultrastructural characterization of tumors and dysplastic and non-neoplastic lesions arising in BK virus/tat transgenic mice. 1023 61

Viral protein R (Vpr) of human immunodeficiency virus type 1 (HIV-1) transiently arrests cells in the G2 phase of the cell cycle and is a weak transcriptional transactivator. We found that Vpr increased HIV-1 long terminal repeat (LTR) activity in all cells examined but, when expressed at high levels, decreased HIV-1 LTR expression due to cytotoxic effects. Moreover, Vpr-mediated enhancement of HIV-1 LTR-driven transcription was observed in cycling primary human CD4(+) T cells but not in terminally differentiated, noncycling primary human macrophages. In single-round infection experiments using primary human CD4(+) T cells, proviral clones expressing either wild-type Vpr or Vpr mutants that retained the ability to cause a G2 arrest replicated to higher levels than proviruses lacking Vpr or expressing mutants of Vpr that did not cause an arrest. In support of the hypothesis that enhancement of HIV-1 LTR transcription by Vpr is an indirect effect of the ability of Vpr to delay cells in G2, counterflow centrifugal elutriation of cells into different phases of the cell cycle demonstrated that HIV-1 LTR expression was highest in G2. Finally, the ability of Vpr to upregulate viral transcription was dependent on a minimal promoter containing a functional TATA box and an enhancer.
 ...
PMID:Cell cycle- and Vpr-mediated regulation of human immunodeficiency virus type 1 expression in primary and transformed T-cell lines. 1036 89

The human immunodeficiency virus type 1 (HIV-1) Tat gene, a potent transactivator of viral and cellular genes, has been proposed as a key agent in the pathogenesis of acquired immune deficiency syndrome related disorders, including non-Hodgkin's lymphoma. In cultured cells, the HIV-1 Tat protein can induce the expression of the cytokines interleukin-6 (IL-6) and IL-10, which are known to induce proliferation and differentiation of lymphoid cells. Such alterations in cytokine expression, together with a secondary genetic event, are thought to ultimately lead to oncogenic transformation. To address the influence of Tat on lymphoid development in the context of the whole organism, we produced several transgenic mouse lines that express the Tat gene under the control of an actin promoter. We show here that this promoter directs expression to a variety of sites, including spleen, bone marrow, and lymph nodes. Approximately 25% to 30% of the Tat-transgenic population developed enlarged spleens within 1 year after birth. On histological examination, a significant number of spleens from Tat-transgenic mice exhibited malignant lymphoma of B-cell origin. IgG heavy chain rearrangement confirmed the clonal B-cell nature of these lymphoproliferations. In contrast, T-cell receptor genes exhibited a germline (unrearranged) structure. Reverse transcription polymerase chain reaction analysis of transgenic spleens revealed that mRNA encoding cytokines IL-6 and IL-10 was upregulated, suggesting a possible mechanism for the B-cell expansion in vivo.
 ...
PMID:Expression of the human immunodeficiency virus-Tat gene in lymphoid tissues of transgenic mice is associated with B-cell lymphoma. 1038 23

Tip60, a cellular histone-acetyltransferase, is known to interact with the HIV-1-encoded transactivator protein, Tat. In this work, we show that the interaction of Tat with Tip60 efficiently inhibits the Tip60 histone-acetyltransferase activity. Besides its histone-acetyltransferase activity, Tip60 can undergo an autoacetylation which is not affected by Tat interaction. Our data show that Tip60 does not significantly influence Tat-dependent transcriptional activation of the 5'-LTR of HIV, suggesting that its interaction with Tat affects some intrinsic cellular process. We were then able to identify a cellular gene, Mn-dependent superoxide dismutase (Mn-SOD), that has a Tip60-dependent transcriptional activity. Interestingly, the simultaneous expression of Tat and Tip60 abolishes the effect of Tip60 on the activity of the Mn-SOD promoter. We postulate that the HIV-1 transactivator, Tat, in targeting Tip60 hinders the expression of cellular genes (such as Mn-SOD) which normally interfere with the efficient replication and propagation of the virus.
 ...
PMID:Control of the histone-acetyltransferase activity of Tip60 by the HIV-1 transactivator protein, Tat. 1039 59

This review is an update on the transforming genes of human cytomegalovirus (HCMV) and human herpesvirus 6 (HHV-6). Both viruses have been implicated in the etiology of several human cancers. In particular, HCMV has been associated with cervical carcinoma and adenocarcinomas of the prostate and colon. In vitro transformation studies have established three HCMV morphologic transforming regions (mtr), i.e., mtrI, mtrII, and mtrIII. Of these, only mtrII (UL111A) is retained and expressed in both transformed and tumor-derived cells. The transforming and tumorigenic activities of the mtrII oncogene were localized to an open reading frame (ORF) encoding a 79-amino-acid (aa) protein. Furthermore, mtrII protein bound to the tumor suppressor protein p53 and inhibited its ability to transactivate a p53-responsive promoter. In additional studies, the HCMV immediate-early protein IE86 (IE2; UL122) was found to interact with cell cycle-regulatory proteins such as p53 and Rb. However, IE86 exhibited transforming activity in vitro only in cooperation with adenovirus E1A. HHV-6 is a T-cell-tropic virus associated with AIDS-related and other lymphoid malignancies. In vitro studies identified three transforming fragments, i.e., SalI-L, ZVB70, and ZVH14. Of these, only SalI-L (DR7) was retained in transformed and tumor-derived cells. The transforming and tumorigenic activities of SalI-L have been localized to a 357-aa ORF-1 protein. The ORF-1 protein was expressed in transformed cells and, like HCMV mtrII, bound to p53 and inhibited its ability to transactivate a p53-responsive promoter. HHV-6 has also been proposed to be a cofactor in AIDS because both HHV-6 and human immunodeficiency virus type 1 (HIV-1) have been demonstrated to coinfect human CD4(+) T cells, causing accelerated cytopathic effects. Interestingly, like the transforming proteins of DNA tumor viruses such as simian virus 40 and adenovirus, ORF-1 was also a transactivator and specifically up-regulated the HIV-1 long terminal repeat when cotransfected into CD4(+) T cells. Finally, based on the interactions of HCMV and HHV-6 transforming proteins with tumor suppressor proteins, a scheme is proposed for their role in oncogenesis.
 ...
PMID:Human cytomegalovirus and human herpesvirus 6 genes that transform and transactivate. 1039 70


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>