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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evaluation of liver biopsies in hepatitis C is aimed at confirming the clinical and serologic diagnosis, grading of necroinflammatory activity, staging of consecutive fibrosis, ruling out or confirming liver diseases of different etiology, and assessment of therapeutic effects. Usually, the course of chronic hepatitis C virus (HCV) infection is slow, with mild inflammatory changes. Nevertheless, even in mild asymptomatic chronic hepatitis C episodes of higher inflammatory activity associated with extensive piecemeal necrosis and porto-central bridging, necrosis can accelerate the course of the disease. For this reason, the traditional, morphologically based classification of chronic hepatitis and the term "chronic persistent hepatitis" have lost their predictive usefulness, especially in hepatitis C. Chronic hepatitis should be characterized by etiologic designation as well as grade and stage of the disease. Portal lymphoid aggregates, some inflammatory bile duct damage and mild steatosis are the most characteristic features by which hepatitis C can be differentiated from other progressive inflammatory liver diseases. Antibodies directed against HCV antigens allow identification of viral proteins by immunohistochemistry. Immunostaining for hepatitis B antigens, for alpha-1-antitrypsin and copper staining are helpful in detecting hepatitis B and congenital liver diseases (Wilson's disease, alpha-1-antitrypsin deficiency) as possible causes of chronic progressive inflammatory liver disease. Centrilobular Mallory's hyalin, identified by immunostaining for ubiquitin in combination with perivenular fibrosis, is helpful in diagnosing concomitant alcoholic liver disease. In our own biopsy material (n = 100) and autopsy material (n = 58), HIV/HCV-coinfected patients have a significantly higher rate of fibrosis and cirrhosis than HIV patients without HCV infection. Hepatitis C can apparently aggravate the course of HIV infection. Our morphologic findings support the clinical observation that chronic HCV infection seems to be the main cause of liver failure, especially in the risk group of HCV/HIV-coinfected hemophiliacs.
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PMID:Histopathologic findings in chronic hepatitis C. 883 87

Recently, a quantitative J correlation technique has been presented that permits measurement of 3Jc'c' in proteins isotopically enriched with 13C [Hu, J.-S. and Bax, A. (1996) J. Am. Chem. Soc., 118, 8170-8171]. Here, we describe an analogous experiment that is less sensitive to transverse 13C' relaxation, which is the principal limiting factor in all 13C-13C long-range correlation experiments on macromolecules. The new scheme utilizes homonuclear Hartmann-Hahn cross polarization (TOCSY) instead of a COSY type transfer to accomplish magnetization transfer; a description of the relevant relaxation terms is presented. The experiment is demonstrated for ubiquitin and HIV-1 Nef. The results show excellent agreement between 3Jc'c' values measured for ubiquitin with the new scheme and those reported previously. The experiment is particularly useful for distinguishing backbone phi angles that are smaller than -120 degrees from those larger than -120 degrees.
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PMID:A three-dimensional NMR experiment with improved sensitivity for carbonyl-carbonyl J correlation in proteins. 909 Jan 34

The pathogenesis of neuropsychological abnormalities in patients with human immunodeficiency virus type 1 (HIV-1) encephalitis is obscure because neurons are not the target of infection and severe neuronal loss occurs only late during the disease. Moreover, there is evidence indicating that HIV dementia is not a homogeneous entity and could partially reverse after treatment with zidovudine. The finding that impaired axonal flow, evidenced by beta-amyloid precursor protein immunoreactivity, could contribute to the neuropsychological deficits prompted the present study. Brains of patients with full-blown acquired immunodeficiency syndrome (AIDS) were studied and findings compared with those of normal and abnormal control subjects. The presence of HIV-1 DNA was investigated by nested polymerase chain reaction; axonal abnormalities were detected by beta-amyloid precursor protein, ubiquitin immunohistochemistry, and silver staining. Accumulation of beta-amyloid precursor protein was observed in all the HIV encephalitis brains studied; the appearance of the immunostaining varied from globular structures to bundles of parallel formations. In 2 AIDS brains without pathological abnormalities, only the latter pattern was detected. The brains with trauma were strongly reactive with beta-amyloid precursor protein antibody and the different reactivity within them correlated with posttrauma survival, only globular structures being detected in the older cases. No correlation was found between the different pattern of beta-amyloid precursor protein reactivity and dementia in AIDS patients. These results show that widespread axonal injury is a constant feature in AIDS brains and suggest that it could play a role in the pathogenesis of the neuropsychological abnormalities of these patients.
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PMID:Accumulation of beta-amyloid precursor protein in HIV encephalitis: relationship with neuropsychological abnormalities. 922 83

The presence of neuropsychological disturbances in HIV-positive, pre-symptomatic individuals is a controversial issue. Neuroimaging studies have not shown brain atrophy or hyperintensity in the white matter, whereas proton magnetic resonance spectroscopy has revealed some abnormality of cerebral biochemistry. Using an antibody to beta-amyloid precursor protein (beta-APP), we previously demonstrated frequent and widespread axonal changes in the brains of AIDS patients. In this study, we extended the use of beta-APP to asymptomatic patients in order to establish a possible morphological correlation with neuropsychological disorders. Brain samples from 29 patients were examined. Results showed bundles of beta-APP-positive axons in 8/29 cases (27%). The changes, seen in both superficial and deep white matter, were either focal or diffuse, could not be visualized by silver or ubiquitin stains, and did not coexist with any change in distribution or morphology of astrocytes and microglial cells. We conclude that in HIV-positive asymptomatic individuals, axonal changes: (a) may be related to the state of immune activation with consequent presence of toxic substances, including cytokines, observed in these patients; (b) may represent mild changes that could undergo repair, unless other pathological events, such as the supervening of the AIDS stage and the specific encephalitis, make them permanent.
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PMID:Axonal damage revealed by accumulation of beta-APP in HIV-positive individuals without AIDS. 937 Feb 37

Host proteins are incorporated into retroviral virions during assembly and budding. We have examined three retroviruses, human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus (SIV), and Moloney murine leukemia virus (Mo-MuLV), for the presence of ubiquitin inside each of these virions. After a protease treatment to remove exterior viral as well as contaminating cellular proteins, the proteins remaining inside the virion were analyzed. The results presented here show that all three virions incorporate ubiquitin molecules at approximately 10% of the level of Gag found in virions. In addition to free ubiquitin, covalent ubiquitin-Gag complexes were detected, isolated, and characterized from all three viruses. Our immunoblot and protein sequencing results on treated virions showed that approximately 2% of either HIV-1 or SIV p6Gag was covalently attached to a single ubiquitin molecule inside the respective virions and that approximately 2 to 5% of the p12Gag in Mo-MuLV virions was monoubiquitinated. These results show that ubiquitination of Gag is conserved among these retroviruses and occurs in the p6Gag portion of the Gag polyprotein, a region that is likely to be involved in assembly and budding.
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PMID:Ubiquitin is covalently attached to the p6Gag proteins of human immunodeficiency virus type 1 and simian immunodeficiency virus and to the p12Gag protein of Moloney murine leukemia virus. 952 17

HIV-1 Vpu interacts with CD4 in the endoplasmic reticulum and triggers CD4 degradation, presumably by proteasomes. Human beta TrCP identified by interaction with Vpu connects CD4 to this proteolytic machinery, and CD4-Vpu-beta TrCP ternary complexes have been detected by coimmunoprecipitation. beta TrCP binding to Vpu and its recruitment to membranes require two phosphoserine residues in Vpu essential for CD4 degradation. In beta TrCP, WD repeats at the C terminus mediate binding to Vpu, and an F box near the N terminus is involved in interaction with Skp1p, a targeting factor for ubiquitin-mediated proteolysis. An F-box deletion mutant of beta TrCP had a dominant-negative effect on Vpu-mediated CD4 degradation. These data suggest that beta TrCP and Skp1p represent components of a novel ER-associated protein degradation pathway that mediates CD4 proteolysis.
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PMID:A novel human WD protein, h-beta TrCp, that interacts with HIV-1 Vpu connects CD4 to the ER degradation pathway through an F-box motif. 966 Sep 40

The HIV-1 protein Vpr is critical for a number of viral functions including a unique ability to arrest T-cells at a G2/M checkpoint and induce subsequent apoptosis. It has been shown to interact specifically with the second UBA (ubiquitin associated) domain found in the DNA repair protein HHR23A, a highly evolutionarily conserved protein. This domain is a commonly occurring sequence motif in some members of the ubiquitination pathway, UV excision repair proteins, and certain protein kinases. The three dimensional structure of the UBA domain, determined by NMR spectroscopy, is presented. The protein domain forms a compact three-helix bundle. One side of the protein has a hydrophobic surface that is the most likely Vpr target site.
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PMID:Structure of a human DNA repair protein UBA domain that interacts with HIV-1 Vpr. 984 73

This study addresses the relationship of epitope-specific Ab responses and alternative autoantibody responses in a model system in which an antigenized self protein serves as the carrier for a defined heterologous B cell epitope. Ubiquitin, a nonimmunogenic self protein, was engineered to present heterologous B and T cell epitopes in the recombinant molecule. Fusion to the C terminus introduced a universal T cell epitope from a Mycobacterium tuberculosis Ag. The B cell epitope was created by inserting a 12-residue loop sequence of HIV-1 gp120 at a surface-exposed position of ubiquitin. These modifications preserved the ubiquitin fold, allowing a new conformational epitope to be presented among native self epitopes. Mice immunized with the hybrid protein bearing only the mycobacterial T cell epitope elicited a strong autoantibody response to native ubiquitin. In contrast, antisera elicited against hybrid ubiquitin presenting the HIV B cell epitope reacted specifically with the foreign epitope but not with native ubiquitin. Absence of autoantibody in the response was attributed to poor competition of autoreactive B cells for limiting T cell help. Both types of responses were associated with Th responses to defined epitopes of the ubiquitin hybrid protein. These results may have implications for a tolerance mechanism dependent on B-T cell cooperation.
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PMID:Epitope-specific antibody and suppression of autoantibody responses against a hybrid self protein. 986 76

The human and simian immunodeficiency viruses (HIV and SIV) downregulate the cell surface expression of CD4, their primary receptor, and of class I histocompatibility complex (MHC-I), a critical mediator of immune recognition. While the first of these effects seems important to preserve viral infectivity, the second likely promotes immune evasion. Three HIV-1 proteins, Nef, Env and Vpu, contribute to downregulate CD4, Env forms a complex with CD4 in the endoplasmic reticulum, thereby retaining the receptor in this compartment. Nef and Vpu, on the other hand, act as connectors between CD4 and specific intracellular trafficking pathways, targeting the receptor for degradation in the lysosome and the proteasome, respectively. Some of the downstream partners of the viral proteins in these events have been identified, and include the adaptor complex of clathrin-coated pits, the beta subunit of COP-I coatomer, and the ubiquitin pathway-related h-beta TrCP protein. HIV-induced MHC-I downregulation, mostly the effect of Nef, also reflects a redistribution of this receptor, with its accumulation in the Golgi. The modalities of this process, however, are as yet imperfectly understood. New evidence indicates that the mechanisms employed by primate lentiviruses to downmodulate CD4 and MHC-I are also exploited by a number of cellular regulatory processes.
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PMID:The downregulation of CD4 and MHC-I by primate lentiviruses: a paradigm for the modulation of cell surface receptors. 1039 64

Recombinant yeast ubiquitin C-terminal hydrolase (YUH1), which has an N-terminal (His)(6) tag, and an autolysis-resistant mutant of the human immunodeficiency virus-1 protease (HIV-1 Pr) have been used as specific proteases to yield peptides from a ubiquitin conjugate. In the present example, connective tissue-activating peptide (CTAPIII) and neutrophil-activating peptide 2 (NAP/2) were generated by digestion of a ubiquitin-CTAPIII conjugate with YUH1 and HIV Pr, respectively, as indicated below: [see text] YUH1 cleaved at the peptide bond formed by the C-terminal Gly(76) of ubiquitin (Ub) and the N-terminal Asn(1) of the 85-residue peptide CTAPIII. The HIV-1 Pr cleaved between Tyr(15) and Ala(16), the N-terminal Ala of the 70-residue peptide NAP/2. Both enzymes produced authentic peptides from the Ub fusion protein, with a nearly 100% yield. The liberated CTAPIII and NAP/2 were separated from (His)(6)-Ub, the trace amounts of unreacted (His)(6)-Ub-CTAPIII, HIV-1 Pr, and the (His)(6)-YUH1 by passage over a nickel-chelate column; the final yield was about 10 mg of peptide/liter of cell culture. (His)(6)-YUH1, the HIV Pr mutant, and the (His)(6)-Ub-CTAPIII substrate were all expressed individually in Escherichia coli. (His)(6)-YUH1 and (His)(6)-Ub-CTAPIII were highly expressed in a soluble form, but about 75% of the total (His)(6)-YUH1 was also found in inclusion bodies. Both proteins from the soluble fractions were easily purified in a single step by immobilized metal ion affinity chromatography with a yield of about 27 mg of (His)(6)-Ub-CTAPIII and 13.6 mg of (His)(6)-YUH1 protein/liter of cell culture. Chemotactic factor activity, as assessed by the neutrophil shape change assay, was observed for NAP/2, but not for CTAPIII. This strategy, which employs YUH1 and the HIV-1 Pr as tools for the highly selective cleavage of the chimeric substrate, should be applicable to the large-scale production of a variety of peptides.
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PMID:Production of chemokines CTAPIII and NAP/2 by digestion of recombinant ubiquitin-CTAPIII with yeast ubiquitin C-terminal hydrolase and human immunodeficiency virus protease. 1041 31


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