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)

The posttranscriptional trans activation of unspliced or partially spliced human immunodeficiency virus RNAs by the Rev regulatory protein is crucial for virus replication and is dependent on sequence-specific RNA binding by Rev. The cognate RNA target of Rev is contained within a highly structured, 244-nucleotide Rev-responsive element (RRE) RNA in the viral env gene. Here, we show that specific interaction with the RRE is not an absolute requirement for Rev function. When the RRE is replaced by a heterologous MS2 phage operator sequence, Rev will facilitate the cytoplasmic expression of human immunodeficiency virus mRNAs containing this sequence if directed to the MS2 operator via the RNA binding motif of the MS2 phage coat protein (MS-C) as a Rev/MS-C fusion protein. Rev/MS-C efficiently activated both RRE and MS2 targets. A mutation in the MS2 operator that abolished the coat protein binding in vitro rendered the mutant RNA nonresponsive to the fusion protein in vivo. Notwithstanding that Rev can be tethered to the viral RNAs via another RNA binding motif, the structural integrity of the N terminus of Rev was still required for optimal trans activation.
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PMID:Human immunodeficiency virus type 1 Rev activation can be achieved without Rev-responsive element RNA if Rev is directed to the target as a Rev/MS2 fusion protein which tethers the MS2 operator RNA. 143 26

The rev protein of human immunodeficiency virus type 1 (HIV-1), a phosphoprotein of 20 kDa apparent molecular weight, is essential to target the mRNA for virion polypeptides into the cytoplasm. So far, at least four necessary functional domains have been assigned to the HIV-1 rev protein: (1) one for RNA binding; (2) a second for nuclear/nucleolar localization that may be indistinguishable from the RNA binding motif; (3) two domains for multimerization; and (4) a putative activation domain (AD) that is suppressed in trans by dominant-negative mutant rev protein. We report three IgG1 kappa mouse monoclonal antibodies (mabs) that were independently raised against rev protein expressed in Escherichia coli. Epitopes are mapped by immunoprecipitation and Western blot screening with 40 different rev mutant peptides. Surprisingly, monoclonal antibodies from all three hybridomas recognized the activation domain of HIV-1 rev.
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PMID:Mouse monoclonal antibodies recognizing the activation domain of HIV-1 rev transactivator. 768 21

Tat (trans-activator) proteins are early RNA binding proteins regulating lentiviral transcription. These proteins are necessary components in the life cycle of all known lentiviruses, such as the human immunodeficiency viruses (HIV) or the equine infectious anemia virus (EIAV). Tat proteins are thus ideal targets for drugs intervening with lentiviral growth. The consensus RNA binding motif (TAR, trans-activation responsive element) of HIV-1 is well characterized. Structural features of the 86 amino acid HIV-1, Zaire 2 isolate (HV1Z2) Tat protein in solution were determined by two dimensional (2D) nuclear magnetic resonance (NMR) methods and molecular dynamics (MD) calculations. In general, sequence regions corresponded to structural domains of the protein. It exhibited a hydrophobic core of 16 amino acids and a glutamine-rich domain of 17 amino acids. Part of the NH2 terminus, Val4 to Pro14, was sandwiched between these domains. Two highly flexible domains corresponded to a cysteine-rich and a basic sequence region. The 16 amino acid sequence of the core region is strictly conserved among the known Tat proteins, and the three-dimensional fold of these amino acids of HV1Z2 Tat protein was highly similar to the structure of the corresponding EIAV Tat domain. HV1Z2 Tat protein contained a well defined COOH-terminal Arg-Gly-Asp (RGD) loop similar to the recently determined decorsin RGD loop.
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PMID:Structural studies of HIV-1 Tat protein. 772 10

The arginine-rich RNA binding motif is found in a wide variety of proteins, including several viral regulatory proteins. Although related at the primary sequence level, arginine-rich domains from different proteins adopt different conformations depending on the RNA site recognized, and in some cases fold only in the context of RNA. Here we show that the RNA binding domain of the Jembrana disease virus (JDV) Tat protein is able to recognize two different TAR RNA sites, from human and bovine immunodeficiency viruses (HIV and BIV, respectively), adopting different conformations in the two RNA contexts and using different amino acids for recognition. In addition to the conformational differences, the JDV domain requires the cyclin T1 protein for high-affinity binding to HIV TAR, but not to BIV TAR. The "chameleon-like" behavior of the JDV Tat RNA binding domain reinforces the concept that RNA molecules can provide structural scaffolds for protein folding, and suggests mechanisms for evolving distinct RNA binding specificities from a single multifunctional domain.
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PMID:An RNA-binding chameleon. 1110 46

The N-proximal region of cowpea chlorotic mottle virus (CCMV) capsid protein (CP) contains an arginine-rich RNA binding motif (ARM) that is also found in the CPs of other members of Bromoviridae and in other RNA binding proteins such as the Tat and Rev proteins of human immunodeficiency virus. To assess the critical role played by this motif during encapsidation, a variant of CCMV RNA3 (C3) precisely lacking the ARM region (C3/Delta919) of its CP gene was constructed. The biology and the competence of the matured CP derived in vivo from C3/Delta919 to assemble and package progeny RNA was examined in whole plants. Image analysis and computer-assisted three-dimensional reconstruction of wild-type and mutant virions revealed that the CP subunits bearing the engineered deletion assembled into polymorphic virions with altered surface topology. Northern blot analysis of virion RNA from mutant progeny demonstrated that the engineered mutation down-regulated packaging of all four viral RNAs; however, the packaging effect was more pronounced on genomic RNA1 and RNA2 than genomic RNA3 and its CP mRNA. In vitro assembly assays with mutant CP subunits and RNA transcripts demonstrated that the mutant CP is inherently not defective in packaging genomic RNA1 (53%) and RNA2 (54%), but their incorporation into virions was competitively inhibited by the presence of other viral RNAs. Northern blot analysis of RNA encapsidation in vivo of two distinct bromovirus RNA3 chimeras, constructed by exchanging CPs having the Delta919 deletion, demonstrated that the role of the conserved N-terminal ARM in recognizing and packaging specific RNA is distinct for each virus.
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PMID:Deletion of highly conserved arginine-rich RNA binding motif in cowpea chlorotic mottle virus capsid protein results in virion structural alterations and RNA packaging constraints. 1573 Dec 22

Human immunodeficiency virus (HIV) codes for a protein, Rev, that mediates the viral RNA export from the nucleus to the cytoplasm. Recently, it has been found that Sam68, the substrate of Src associated in mitosis, is a functional homologue of Rev, and a synergistic activator of Rev activity. Thus, it has been suggested that Sam68 may play an important role in the post-transcriptional regulation of HIV. Sam68 contains an RNA binding motif named KH [homology to the nuclear ribonucleoprotein (hnRNP) K]. Tyrosine phosphorylation of Sam68 and binding to SH3 domains have been found to negatively regulate its RNA binding capacity. Besides, tyrosine phosphorylation of Sam68 allows the formation of signalling complexes with other proteins containing SH2 and SH3 domains, suggesting a role in signal transduction of different systems in human lymphocytes, such as the T cell receptor, and leptin receptor, or the insulin receptor in other cell types. In the present work, we have found that Sam68 is tyrosine phosphorylated in peripheral blood mononuclear cells (PBMC) from HIV infected subjects, leading to the formation of signalling complexes with p85 the regulatory subunit of PI3K, GAP and STAT-3, and decreasing its RNA binding capacity. In contrast, PBMC from HIV infected subjects have lower expression levels of Sam68 compared with controls. These results suggest that Sam68 may play some role in the immune function of lymphocytes in HIV infection.
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PMID:Sam68 is tyrosine phosphorylated and recruited to signalling in peripheral blood mononuclear cells from HIV infected patients. 1604 42