Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0021051 (immunodeficiency)
71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

New West African human immunodeficiency viruses (HIV-2s) and simian immunodeficiency virus (SIV) contain functional transactivator (tat) gene and tat response elements. Their long terminal repeats (LTR) and tat genes are more related among themselves than to HIV-1 LTR and tat gene. The viral gene expression of HIV-2 as well as SIV can be stimulated by T cell activators, such as mitogens and phorbol esters. HIV-2 and SIV display a much broader transactivation response specificity than does HIV-1. The LTR-directed gene expression of HIV-2/SIV is not only transactivated by their own tat gene and by HIV-1 tat gene but also by factors in human T cell leukemia/lymphoma virus type I (HTLV-I) and simian virus 40 (SV40) infected cells, involving HTLV-I tat gene and SV40 T antigens, respectively. HIV-1 LTR-directed gene expression is much less transactivated by HIV-2/SIV tat genes and by factors in HTLV-I- and SV40-infected cells. Immune activation and heterologous transactivation of the LTR-directed gene expression may be relevant to the latency of virus infection and progression toward the acquired immunodeficiency syndrome (AIDS).
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PMID:Human and simian immunodeficiency retroviruses: activation and differential transactivation of gene expression. 284 Jan 5

Simian immunodeficiency virus from rhesus macaques (SIVmac), like human immunodeficiency virus type 1 (HIV-1), encodes a transactivator (tat) which stimulates long terminal repeat (LTR)-directed gene expression. We performed cotransfection assays of SIVmac and HIV-1 tat constructs with LTR-CAT reporter plasmids. The primary effect of transactivation for both SIVmac and HIV-1 is an increase in LTR-directed mRNA accumulation. The SIVmac tat gene product partially transactivates an HIV-1 LTR, whereas the HIV-1 tat gene product fully transactivates an SIVmac LTR. Significant transactivation is achieved by the product of coding exon 1 of the HIV-1 tat gene; however, inclusion of coding exon 2 results in a further increase in mRNA accumulation. In contrast, coding exon 2 of the SIVmac tat gene is required for significant transactivation. These results imply that the tat proteins of SIVmac and HIV-1 are functionally similar but not interchangeable. In addition, an in vitro-generated mutation in SIVmac tat disrupts splicing at the normal splice acceptor site at the beginning of coding exon 2 and activates a site approximately 15 nucleotides downstream. The product of this splice variant stimulates LTR-directed gene expression. This alternative splice acceptor site is also used by a biologically active provirus with an efficiency of approximately 5% compared with the upstream site. These data suggest that a novel tat protein is encoded during the course of viral infection.
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PMID:Functional comparison of transactivation by simian immunodeficiency virus from rhesus macaques and human immunodeficiency virus type 1. 284 68

The long terminal repeats (LTRs) of the human immunodeficiency virus type 2 (HIV-2) and a related simian immunodeficiency virus (SIVmac) contain cis-acting positive regulatory elements upstream and the major transactivator gene (tat) response element and a possible negative regulatory element downstream of the transcriptional initiation site. The tat response element of HIV-2 and of SIVmac was more complex than that of HIV-1. Two structurally similar subelements within the HIV-2 tat response element could be identified. Both of these subelements were required for optimal transactivation by the HIV-2 tat gene product. Either of these subelements, however, was sufficient for transactivation by the HIV-1 tat gene product. These observations provide an explanation for the poor transactivation of HIV-1 LTR-directed gene expression by the HIV-2 tat gene product since the HIV-1 LTR contains an analog of only one of the HIV-2 subelements. The HIV-2 tat gene product also affected the function of the upstream elements, including enhancer activity. The response of these cis elements of HIV-2 to transactivation by HIV-2/SIVmac and HIV-1 tat gene differed somewhat in virus-infected and tat gene transfected cells, probably related to the differences in the effective concentration of the tat gene products and/or other viral or cellular factors. The steady-state levels of HIV-2 LTR-linked gene transcripts were much higher in the presence of HIV-2, SIVmac, and HIV-1 tat genes than in their absence, suggesting transcriptional modulation as a mechanism for tat gene function.
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PMID:Human immunodeficiency virus type 2 long terminal repeat: analysis of regulatory elements. 284 15

Human immunodeficiency virus 1 has been implicated as the main etiologic agent of the acquired immunodeficiency syndrome. However, other infectious agents may accelerate the progression of this disease. In particular, hepatitis B virus has been suggested as one such cofactor. Therefore, we have investigated the effects of hepatitis B virus gene products on expression of the human immunodeficiency virus I in transient transfection studies of Jurkat lymphoblastic T cells, using as reporter the chloramphenicol acetyltransferase gene coupled to the long terminal repeat of human immunodeficiency virus I. As measured by the amount of chloramphenicol acetyltransferase activity, gene expression directed by the human immunodeficiency virus I long terminal repeat increased approximately 10-fold in response to the hepatitis B virus X protein. This trans-activation by the X protein is multiplicative with the effect of phorbol esters and can be accounted for by an increase in the steady-state level of chloramphenicol acetyltransferase mRNA. Analysis of deletion and clustered point mutants in the long terminal repeat indicated that the X protein exerts its effect through multiple cis-acting sites. These results provide a possible molecular basis for the association of hepatitis B virus and the acquired immunodeficiency syndrome and confirm that the X protein is a transcriptional transactivator.
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PMID:Trans-activation of the human immunodeficiency virus long terminal repeat by the hepatitis B virus X protein. 318 23

Human foamy virus (HFV) comprises a complex genomic organization of gag, pol, env, and several nonstructural genes such as bel1, bel2, bel3, bet, beo, and bes located between env and 3' LTR. Among these viral nonstructural genes, bel1 appears to encode an essential transactivator of LTR-directed gene expression. To investigate the roles of the other nonstructural proteins for the viral replication, a series of proviral mutants were generated and tested for their in vitro replication. The mutations in the other than bel1 open reading frame did not show any significant effect on viral replication. The bel1 protein is the only essential transactivator for the LTR-directed transcription. To determine whether HFV has an essential post-transcriptional transactivator like the rev protein of human immunodeficiency virus type 1, or the rex protein of human T cell leukemia virus type 1, we investigated the bel1-independent expression of the HFV gag structural gene under the control of the heterologous simian virus 40 promoter. We demonstrated that the expression of the HFV gag structural gene does not require an essential post-transcriptional transactivator. Thus, it appears that the regulation of HFV gene expression is distinct from that of other human retroviruses.
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PMID:The gene expression of human foamy virus does not require a post-transcriptional transactivator. 752 74

The regulation of transcriptional elongation plays a central role in the expression of a number of cellular and viral genes. For example, levels of c-myc RNA change during cellular proliferation and differentiation via alterations in transcriptional attenuation near the 5' end of the c-myc gene. The protein that regulates transcription through attenuation sites in c-myc has not been identified. However, a candidate protein of equivalent function exists in the human immunodeficiency virus (HIV) genome, where the transactivator Tat increases transcriptional elongation through the HIV LTR and coding sequences by interacting with the trans-acting-response (TAR) RNA stem-loop that is found at the 5' end of all viral transcripts. By placing TAR 3' to the P2 promoter of the mouse c-myc gene, we demonstrate that Tat can also direct read-through transcription in mouse c-myc in transfected HeLa cells. Thus we identified a viral transactivator whose cellular counterpart regulates transcriptional attenuation within c-myc and other proto-oncogenes.
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PMID:Human immunodeficiency virus type 1 tat directs transcription through attenuation sites within the mouse c-myc gene. 752 69

Structural gene expression of human immunodeficiency virus type 1 (HIV-1) requires a viral regulatory protein, Rev transactivator. We investigated Rev-dependency of HIV-1 gene expression by various reporter systems. Expression of unspliced and single-spliced viral mRNAs was demonstrated to be differentially dependent on the Rev function. This difference of Rev-dependency was found not to be determined by cis-elements in gag, pol, and env coding sequences reported so far, and was lost when the reporter constructs containing minimum elements for Rev-responsiveness such as splice signals and rev responsive element were used for experiments. These findings indicated that the fundamental structure of HIV-1 mRNA was critical for the differential regulation of gene expression by Rev transactivator.
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PMID:Rev-dependency of expression of human immunodeficiency virus type 1 gag and env genes. 754 Jan 50

Mounting experimental evidence suggests that the TAT protein, released from human immunodeficiency virus-1 (HIV-1)-infected inflammatory cells, may genetically reprogram targeted cells within a localized environment to develop highly vascularized tumors of mesenchymal origin. The fibroblast growth factor (FGF) family of polypeptides has gained general acceptance as initiators of angiogenesis and functions as potent mitogens for mesoderm-derived cells. To evaluate a potential biological relationship between TAT and acidic FGF (FGF-1), primary murine embryonic fibroblasts either were transfected with the viral transactivator or were transduced (retrovirally mediated) with a secreted, chimeric form of the human polypeptide growth factor, human stomach tumor/Kaposi's sarcoma (hst/KS)FGF-1. Reverse transcriptase-polymerase chain reaction, Western blotting, in situ immunohistochemical, heparin affinity, DNA synthesis, and transient transfection techniques were used to confirm expression, localization, and functionality of the transgenes. Both transfected and transduced cells constitutively expressing either TAT or (hst/KS)FGF-1 adopted a transformed phenotype, maintained aggressive growth behavior, and demonstrated both induction of FGF-specific phosphotyrosyl proteins and nuclear association of FGF-1 and FGF-1 receptor. Increased levels of endogenous, murine FGF-1 mRNA (reverse transcriptase-polymerase chain reaction) and protein (immunoblot analysis) were apparent in both (hst/KS)FGF-1- and TAT-transformed cells. Medium conditioned by (hst/KS)FGF-1-transduced cells contained steady-state levels of biologically active FGF-1 which exhibited a representative molecular weight. Limited sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of the conditioned medium from TAT-transformed cells demonstrated the appearance of FGF-1 as latent, high molecular weight complexes requiring reducing agents to activate full biological activity. Collectively, these results suggest that TAT induces the expression and secretion of FGF-1, which may be potentially relevant to the pathophysiological development of AIDS-Kaposi's sarcoma.
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PMID:The HIV-1 TAT protein induces the expression and extracellular appearance of acidic fibroblast growth factor. 754 39

Class II major histocompatibility complex (MHC) genes and the invariant (Ii) gene are inducible by interferon-gamma (IFN gamma) but not by interferon-alpha and interferon-beta. The promoter regions of these genes contain three regulatory elements that mediate constitutive and IFN gamma-induced expressions; however, none of the DNA-binding proteins that interact with these elements are regulated by IFN gamma. Recently, a gene coding for a transactivator (CIITA) of class II MHC genes that complements a HLA-DR-negative immunodeficiency has been isolated. Using one IFN gamma mutant cell line (G3A) that is selectively defective in HLA-DR and Ii induction, four lines of evidence are presented to show that CIITA mediates the IFN gamma induction of HLA-DR and Ii genes. Analysis of another mutant line, G1B, indicates that the lack of DRA and Ii gene induction by IFN gamma is correlated with the lack of RFX DNA binding activity, thus providing the link between RFX and an IFN gamma response.
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PMID:Molecular analysis of G1B and G3A IFN gamma mutants reveals that defects in CIITA or RFX result in defective class II MHC and Ii gene induction. 760 Feb 94

tat protein, a human immunodeficiency virus (HIV) gene product that functions as a transactivator for HIV replication, is known to be secreted extracellularly by infected cells. To determine the potential role of tat in the dissemination of HIV into extravascular tissue, this protein was examined for its ability to activate human endothelial cells. The results show that tat does indeed stimulate endothelial cells. This is evidenced by their expression of the endothelial-leukocyte adhesion molecules, E-selectin, critical for the initial binding of leukocytes to the blood vessel wall, and their increased synthesis of interleukin-6 (IL-6), a cytokine known to enhance endothelial cell permeability. Furthermore, tat acts synergistically with low concentrations of tumor necrosis factor-alpha to enhance IL-6 secretion. These data suggest that extracellular tat protein secreted or released into the microenvironment may contribute significantly to the determination of specific sites of leukocyte binding to blood vessels, to transmigration into tissue, and to eventual dissemination of HIV-infected cells or free virions into tissue.
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PMID:Exogenous tat protein activates human endothelial cells. 751 13


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