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 abnormal isoforms of the normal cellular prion protein (PrP), also termed Scrapie-associated fibril protein, are assumed to be one causative factor of spongiform encephalopathies. The mRNA of PrP contains stem-loop structures which are very similar to the human immunodeficiency virus-1 (HIV-1) cis-acting sequence TAR within the LTR; both structures contain the pentanucleotide CUGGG in the loop, and the uridine- and adenine-bulge in the stem. In this study, using purified HIV-encoded trans-activator, Tat, and HIV-1 TAR-RNA or PrP-mRNA containing the stem-loop structure, we demonstrate by use of gel-retardation and filter binding assays that Tat binds to TAR- and PrP-RNA with the dissociation constants of 2.9 or 37.0 nM, respectively, at a molar ratio of 0.7 mol of Tat to 1 mol of RNA fragment. The Tat-RNA (TAR or PrP) complexes bind to protein(s) in the nuclear matrix, isolated from human astrocytes (glial fibrillary acidic protein positive brain cells). Infection of astrocytes with HIV-1 resulted in an increased level of PrP mRNA. The data presented led us to assume that certain sequences in the PrP mRNA might be targets for proteins acting in trans.
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PMID:Accumulation of transcripts coding for prion protein in human astrocytes during infection with human immunodeficiency virus. 135 48

The RNA stem-loop structure of the trans-activating region TAR sequence of human immunodeficiency virus-1 mRNA is the binding site for a number of host cell proteins. A virtually identical set of proteins from HeLa nuclear extracts was found to bind to the predicted RNA hairpin element of prion protein (PrP) mRNA, as demonstrated in UV cross-linking/RNase protection and Northwestern assays. We show that the cellular TAR loop-binding protein, p68, is among those proteins which associate with PrP RNA. Competition experiments with various TAR RNA mutants revealed that binding of partially purified p68 to PrP RNA stem-loop occurs sequence-specifically. The 100-kDa 2-5A synthetase which is involved in the cellular antiviral defense was able to bind to PrP mRNA stem-loop in Northwestern blots with cytosolic proteins from HeLa cells treated with interferon. However, the PrP RNA failed to activate this enzyme in vitro, in contrast to TAR RNA.
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PMID:Interaction of 68-kDa TAR RNA-binding protein and other cellular proteins with prion protein-RNA stem-loop. 922 82

Investigation of human antibody responses to viral pathogens at the molecular level is revealing novel aspects of the interplay of viruses with the humoral immune system. In viral infection, at least two types of human antibody responses exist: a response to mature envelope on virions that is neutralizing and a response to immature forms of envelope (viral debris) that is not. Many pathogens have, to varying degrees, evolved envelopes to minimize antibody responses against epitopes exposed on the virion. In this article, we review recent studies on human immunodeficiency virus type 1, Ebola virus, and respiratory syncytial virus. Prion diseases are diseases of protein conformation. We have generated a large panel of antibodies recognizing the cellular prion protein (PrP(c)), some of which also react with the abnormally folded infectious prion protein (PrP(Sc)). These antibodies are being used to gain insight into both the molecular events leading to the formation of infectious PrP and the physiologic role played by PrP in normal and prion-infected cells.
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PMID:Antibodies in human infectious disease. 1085 27

Prion replication in spleen and neuroinvasion after i.p. inoculation of mice is impaired in forms of immunodeficiency where mature B lymphocytes are lacking. In spleens of wild-type mice, infectivity is associated with B and T lymphocytes and stroma but not with circulating lymphocytes. We generated transgenic prion protein knockout mice overexpressing prion protein in B lymphocytes and found that they failed to accumulate prions in spleen after i.p. inoculation. We conclude that splenic B lymphocytes are not prion-replication competent and that they acquire prions from other cells, most likely follicular dendritic cells with which they closely associate and whose maturation depends on them.
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PMID:B lymphocyte-restricted expression of prion protein does not enable prion replication in prion protein knockout mice. 1127 28

Transmissible spongiform encephalopathies are fatal neurodegenerative diseases associated with the accumulation of a protease-resistant form of the prion protein (PrP). Although PrP is conserved in vertebrates, its function remains to be identified. In vitro PrP binds large nucleic acids causing the formation of nucleoprotein complexes resembling human immunodeficiency virus type 1 (HIV-1) nucleocapsid-RNA complexes and in vivo MuLV replication accelerates the scrapie infectious process, suggesting possible interactions between retroviruses and PrP. Retroviruses, including HIV-1 encode a major nucleic acid binding protein (NC protein) found within the virus where 2000 NC protein molecules coat the dimeric genome. NC is required in virus assembly and infection to chaperone RNA dimerization and packaging and in proviral DNA synthesis by reverse transcriptase (RT). In HIV-1, 5'-leader RNA/NC interactions appear to control these viral processes. This prompted us to compare and contrast the interactions of human and ovine PrP and HIV-1 NCp7 with HIV-1 5'-leader RNA. Results show that PrP has properties characteristic of NCp7 with respect to viral RNA dimerization and proviral DNA synthesis by RT. The NC-like properties of huPrP map to the N-terminal region of huPrP. Interestingly, PrP localizes in the membrane and cytoplasm of PrP-expressing cells. These findings suggest that PrP is a multifunctional protein possibly participating in nucleic acid metabolism.
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PMID:The prion protein has RNA binding and chaperoning properties characteristic of nucleocapsid protein NCP7 of HIV-1. 1127 62

Interaction between nucleic acid and recombinant murine prion protein, MoPrPC resulted in a time-dependent change in the nucleic acid morphology revealed by electron microscopy. After the addition of the protein to DNA, association of small number of nucleic acid molecules (nucleo-protein complex) was followed by aggregation of large number of them still retaining their initial linear morphology. With increase in the incubation time, ordered aggregation resulted in small condensed spherical globules. Subsequently, the formation of large condensed particles took place either by fusion of the already formed small globules or by accumulation of more nucleic acid molecules on them. The condensed nucleic acid structures observed here were different from other known morphologically altered nucleic acid structures induced by different cellular proteins. The condensed nucleic acid structures dissociated spontaneously. The formation of the prion protein-induced condensed nucleic acid structures resembled the human immunodeficiency virus 1 nucleocapsid protein NCp7-induced condensed ordered aggregates of nucleic acids. In the latter system, both the processes of condensation and dissociation of the nucleoprotein complex are believed to be responsible for the functional properties of the HIV-1 virus. Demonstration of functional activity of the prion protein-nucleic acid complex would be relevant for a role of nucleic acid in prion diseases.
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PMID:Murine recombinant prion protein induces ordered aggregation of linear nucleic acids to condensed globular structures. 1131 41

The V3 loop of the human immunodeficiency virus (HIV)-1 surface envelope glycoprotein gp120 is a sphingolipid-binding domain mediating the attachment of HIV-1 to plasma membrane microdomains (rafts). Sphingolipid-induced conformational changes in gp120 are required for HIV-1 fusion. Galactosylceramide and sphingomyelin have been detected in highly purified preparations of prion rods, suggesting that the prion protein (PrP) may interact with selected sphingolipids. Moreover, a major conformational transition of the Alzheimer beta-amyloid peptide has been observed upon interaction with sphingolipid-containing membranes. Structure similarity searches with the combinatorial extension method revealed the presence of a V3-like domain in the human prion protein PrP and in the Alzheimer beta-amyloid peptide. In each case, synthetic peptides derived from the predicted V3-like domain were found to interact with monomolecular films of galactosylceramide and sphingomyelin at the air-water interface. The V3-like domain of PrP is a disulfide-linked loop (Cys(179)-Cys(214)) that includes the E200K mutation site associated with familial Creutzfeldt-Jakob disease. This mutation abrogated sphingomyelin recognition. The identification of a common sphingolipid-binding motif in gp120, PrP, and beta-amyloid peptide underscores the role of lipid rafts in the pathogenesis of HIV-1, Alzheimer, and prion diseases and may provide new therapeutic strategies.
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PMID:Identification of a common sphingolipid-binding domain in Alzheimer, prion, and HIV-1 proteins. 1179 5

All lentiviruses and oncoretroviruses examined so far encode a major nucleic-acid binding protein (nucleocapsid or NC* protein), approximately 2500 molecules of which coat the dimeric RNA genome. Studies on HIV-1 and MoMuLV using in vitro model systems and in vivo have shown that NC protein is required to chaperone viral RNA dimerization and packaging during virus assembly, and proviral DNA synthesis by reverse transcriptase (RT) during infection. The human cellular prion protein (PrP), thought to be the major component of the agent causing transmissible spongiform encephalopathies (TSE), was recently found to possess a strong affinity for nucleic acids and to exhibit chaperone properties very similar to HIV-1 NC protein in the HIV-1 context in vitro. Tight binding of PrP to nucleic acids is proposed to participate directly in the prion disease process. To extend our understanding of lentiviruses and of the unexpected nucleic acid chaperone properties of the human prion protein, we set up an in vitro system to investigate replication of the feline immunodeficiency virus (FIV), which is functionally and phylogenetically distant from HIV-1. The results show that in the FIV model system, NC protein chaperones viral RNA dimerization, primer tRNA(Lys,3) annealing to the genomic primer-binding site (PBS) and minus strand DNA synthesis by the homologous FIV RT. FIV NC protein is able to trigger specific viral DNA synthesis by inhibiting self-priming of reverse transcription. The human prion protein was found to mimic the properties of FIV NC with respect to primer tRNA annealing to the viral RNA and chaperoning minus strand DNA synthesis.
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PMID:Functional interactions of nucleocapsid protein of feline immunodeficiency virus and cellular prion protein with the viral RNA. 1205 75

The reconstitution of blood and its components is hampered by factors of compatibility, availability, and the risk of transmission of infectious diseases. Protozoal agents such as plasmodium malariae and trypanosoma cruzi are only regionally relevant. Bacterial transmissions are easy to prevent and treat. Antibody, antigen, and nucleic acid screening have been implemented to prevent transmission of blood-borne viruses. Transfusion-relevant viruses include hepatitis B and C virus (HBV and HCV), human immunodeficiency virus (HIV), human T leukemia virus (HTLV-I), and in certain circumstances, parvovirus B19, hepatitis A virus (HAV), and cytomegalovirus (CMV). Of great concern is the possible transmission of prion protein causing transmissible spongiform encephalopathy. Of future interest will be whether other viruses such as Nipah and Hendra virus are blood-borne and whether viruses such as TT, SEN, and GBV-C are involved in diseases or their progression, while not causing hepatitis.
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PMID:Virus safety of human blood, plasma, and derived products. 1237 92

The ubiquitously expressed cyclin T1 gene encodes for a protein involved in human immunodeficiency virus type 1 (HIV-1) transcription activation. The goat gene was recently shown to share an expression pattern similar to that of its endogenous counterpart when incorporated into mice using a BAC insert. To assess if its promoter could target ubiquitous expression of the bovine Prnp in transgenic mice, two constructs carrying either 1 or 30 kb of cyclin T1 5'-flanking sequences were built and microinjected. Both constructs resulted in the unexpected high male germ cell-specific expression of the prion protein. These data re-question the suspected location of the cyclin T1 gene regulatory elements.
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PMID:Unexpected high testis-specific transcriptional activity of the cyclin T1 promoter in transgenic mice. 1291 44


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