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

The retroviral integrase (IN) protein is essential for integration of retroviral DNA into the host cell genome. To identify functional domains within the protein and to assess the importance of conserved residues, we performed site-directed mutagenesis of HIV-1 IN and analyzed the mutants in vitro for IN-mediated activities: 3' processing (att site-specific nuclease activity), strand transfer (the joining of att site oligonucleotides to target DNA), disintegration (the reverse of strand transfer), and integration site selection. Changing the conserved residue His-16 either to Cys or to Val in a proposed zinc-finger region had minimal effect on IN activities. Alteration of two highly conserved amino acid residues, Asp-116-->Ile and Glu-152-->Gly, each resulted in complete or nearly complete loss of 3' processing, strand transfer, and disintegration, whereas alteration of another conserved residue, Trp-235-->Glu, had no demonstrable effect on any of the activities in vitro. Two mutants, Asp-64-->Val and Arg-199-->Cys delta, each demonstrated differential effects on IN activities. Asp-64-->Val has no demonstrable strand transfer or disintegration activity yet maintains 3' processing activity at a diminished level. Arg-199-->Cys delta, which lacks part of the carboxyl terminus of IN, has impaired strand transfer activity without loss of disintegration activity. Use of a target site selection assay showed that all of our mutants with strand transfer activity maintain the same integration pattern as wild type IN. We conclude that not all highly conserved IN residues are essential for IN activities in vitro, zinc coordination by the proposed zinc-finger domain may not be required for the activities assayed, alteration of single residues can yield differential effects on IN activities, and target site selection into naked DNA is not necessarily altered by changes in strand transfer activity.
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PMID:Site-directed mutagenesis of HIV-1 integrase demonstrates differential effects on integrase functions in vitro. 842 Sep 82

Retroviral nucleocapsid and gag-precursor proteins from all known strains of retroviruses contain one or two copies of an invariant sequence, Cys-X2-Cys-X4-His-X4-Cys, that is populated with zinc in mature particles. Modification of cysteine or histidine residues results in defective packaging of genomic viral RNA and formation of non-infectious particles, making these structures potentially attractive targets for antiviral therapy. We recently reported that aromatic C-nitroso ligands of poly(ADP-ribose) polymerase preferentially destabilize one of the two (Cys-X2-Cys-X28-His-X2-Cys) zinc-fingers with concomitant loss of enzymatic activity, coincidental with selective cytocidal action of the C-nitroso substituted ligands on cancer cells. Based on the occurrence of (3Cys, 1His) zinc-binding sites in both retroviral nucleocapsid and gag proteins and in poly(ADP-ribose) polymerase, we reasoned that the C-nitroso compounds may also have antiretroviral effects. We show here that two such compounds, 3-nitrosobenzamide and 6-nitroso-1,2-benzopyrone, inhibit infection of human immunodeficiency virus HIV-1 in human lymphocytes and also eject zinc from isoalted HIV-1 nucleocapsid zinc fingers and from intact HIV-1 virions. Thus the design of zinc-ejecting agents that target retroviral zinc fingers represents a new approach to the chemotherapy of AIDS.
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PMID:Inhibition of HIV-1 infectivity by zinc-ejecting aromatic C-nitroso compounds. 842 89

Mads Melbye was awarded the Anders Jahre prize for young scientists in 1992 for his research into epidemiological infections. His pioneering work, which has elucidated the manner in which HIV and AIDS are transmitted sexually and via contaminated blood, has been of fundamental importance in understanding AIDS as an infectious disease. The article describes how this knowledge was obtained, and how it has added to our understanding of the pathogenesis of other diseases--here exemplified by a type of cancer.
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PMID:[The Anders Jahre Prize for young researchers 1992. HIV/AIDS--an epidemiological challenge]. 845 74

In Stockholm county, which has 70% of all HIV cases in Sweden, the situation is disconcerting because asylum seekers and migrants from Africa seem to find it difficult to follow the rules that HIV-infected persons must observe to limit the spread of the infection. In Sweden, regulations have been established for fighting infectious diseases with treatment, infection and contact tracking, and reporting obligation. 44 (17%) of 266 HIV-infected Africans in Stockholm county have been the target of some kind of intervention from infection control doctors. Since 1989 all asylum seekers have been offered testing for HIV. 5 cases are described, 3 of whom had to be placed in forced isolation. The 1st case was a 25-year old African man who came to Sweden in 1990 and sought political asylum, during which procedure HIV infection was confirmed. He was instructed about the rules concerning infection control orally and in written form. Then he met a Swedish woman whom he infected failing to reveal that he was HIV-positive and failing to use a condom. When contacted, he did not disclose his previous infection. He got married. His failure to report was eventually detected and also the fact that he had had at least 2 more contacts. Request to put him into isolation was denied owing to his current relationship. In another case, a teenage African was found HIV-seropositive in 1988 and subsequently infected a 16-year-old Swedish girl and later another woman without revealing his infection. He was confined to forced isolation. A 3rd case involved a 36-year alcoholic African with HIV infection who escaped from confinement and eventually was put in forced isolation. Since there are so many heterosexually infected people who deny their infection, it is arguable whether they should be granted a residency permit when they do not respect the Swedish regulations.
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PMID:[HIV-positive Africans spread the infection. Many of them ignore the rules of protection against the infection]. 850 10

We showed previously that a commercially available synthetic tetradecapeptide, Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Val-Tyr-Ser, produces authentic angiotensin I (Ang I) upon incubation with the HIV-1 protease (S. K. Sharma et al., Anal. Biochem. 198:363, 1991). Therefore, we developed an Ang-I based activity assay for HIV protease inhibitors based on the technology developed earlier (M. J. Ruwart et al., Pharm. Res. 7:407, 1990; S. K. Sharma et al., Anal. Biochem. 186:24, 1990) for tracking renin inhibitors in rat sera. Ditekiren was either extracted from sera with ethyl acetate or assayed after the interfering substances in sera were precipitated with acetonitrile. Purified recombinant HIV-1 protease was added to extracted rat serum and the enzymatic reaction was initiated in the presence of the tetradecapeptide substrate. The inhibition of Ang I production was measured by a commercially available RIA kit. The cleanup methodology also enabled a commercially available Proteinase Scintillation Proximity Assay (SPA, Amersham) to quantify ditekiren in rat serum through the addition of recombinant HIV-1 protease and cleavage of substrate from SPA beads. Results were confirmed by HPLC or by the renin assay for ditekiren, which inhibits both aspartyl proteases. These technologies should prove useful for assessing serum levels of HIV protease inhibitors in rat.
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PMID:Development of activity assays for high-volume evaluation of human immunodeficiency virus (HIV) protease inhibitors in rat serum: results with ditekiren. 848 39

The highly conserved zinc fingers in retroviral nucleocapsid (NC) proteins have the general structure Cys-(X)2-Cys-(X)4-His-(X)4-Cys. Human immunodeficiency virus type 1 (HIV-1) contains two Zn2+ fingers, and mutants were constructed in which the native sequence of each Zn2+ finger was maintained but their positions in the NC protein were changed. Mutants had either two first-finger sequences (pNC1/1), two second-finger sequences (pNC2/2), or reversed first- and second-finger sequences (pNC2/1). Cells transfected with mutant or wild-type clones produced similar levels of Tat, Gag, Pol, and Env proteins, formed syncytia, and shed viruslike particles that were indistinguishable by electron microscopy. However, the pNC2/1 and pNC2/2 mutants were inefficient in packaging genomic RNA (less than 15% of wild-type levels), whereas the pNC1/1 mutant packaged approximately 70% of wild-type levels of RNA. No infectious virus could be detected with either the pNC2/1 or pNC2/2 mutants, whereas the pNC1/1 mutant appeared to sustain a low level of replication and reverted to a competent wild-type-like viral species after a 2- to 4-week lag period. The data strongly suggest that the two Zn2+ fingers of HIV-1 are not functionally equivalent and that the first Zn2+ finger in the Gag precursor plays a more prominent role in RNA selection and packaging. The data also indicate that both Zn2+ fingers in the mature NC protein play as yet unknown roles in viral assembly or the early stages of the viral infection process.
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PMID:The two zinc fingers in the human immunodeficiency virus type 1 nucleocapsid protein are not functionally equivalent. 851 Feb 14

HIV-EP1 is a C2H2 type zinc finger protein which binds to DNA kappa B site present in the long terminal repeat of HIV provirus. Previously we have reported zinc chelators having histidine--pyridine--histidine skeleton and were successful in inhibiting the DNA binding of HIV-EP1 by removing zinc from the zinc finger domain. Aiming at the potentiation of the inhibitory activity of our previous zinc chelators, herein synthesized were novel chelators comprising pyridine and aminoalkanethiol. These showed marked inhibitory activity on the DNA binding of HIV-EP1. In particular, one of them having a bis(2-mercaptoethyl) amino side chain showed inhibitory activity (IC50, approximately 4 microM) 10 times stronger than that of the strongest inhibitor that we reported previously. It appeared that these inhibited the DNA binding of HIV-EP1 by a mechanism distinct from that of the previous histidine-based inhibitors.
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PMID:Metal-chelating inhibitors of a zinc finger protein HIV-EP1. Remarkable potentiation of inhibitory activity by introduction of SH groups. 855 19

We report a 29-year-old male hemophiliac with human immunodeficiency virus (HIV)-1-associated dementia complex, who died 2.5 months after the onset of dementia. The patient's cognitive abnormalities including forgetfulness, loss of concentration and slowing of thought appeared about 7 years after HIV infection. His neurological symptoms were characterized as progressive dementia, episodic consciousness loss, transverse myelopathy and peripheral neuropathy. He had generalized slow waves in electroencephalogram (EEG), progressive cerebral atrophy and a diffuse high intensity lesion in the white matter as shown by T2-weighted brain magnetic resonance imaging (MRI). We emphasize the significance of neurological complications, especially acute progressive dementia, in Japanese patients with acquired immunodeficiency syndrome (AIDS).
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PMID:A hemophiliac with human immunodeficiency virus (HIV)-1-associated dementia complex. 856 90

To produce the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) in amounts required to study its structure and function, the p66 enzyme subunit was expressed using two different baculovirus vectors in Sf158 insect host cells. Both vectors permitted an efficient HIV-1 RT expression. The resulting products were purified up to 90% homogeneity, characterized, and investigated for their susceptibility to digestion with various proteases. The recombinant baculoviral RT obtained with the pAc373 expression vector was purified as a p66/p60 heterodimer. The recombinant His-RT was expressed with the pBlueBacHis vector. Thereby, the protein was tagged with an N-terminal hexahistidine peptide and it was purified as a p70/p70 homodimer. The two enzymes differed in their specific activity, kinetic properties, and in vitro activation by viral and non-viral proteases. The recombinant His-RT exhibited a lower specific activity than the recombinant RT. The latter yielded enzyme activities as high as an Escherichia coli-expressed RT. Removal of the hexahistidine tag from the recombinant His-RT by digestion with enterokinase resulted in a complete loss of enzyme activity. Thus, the hexahistidine tag might be an intrinsic part of the active recombinant His-RT.
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PMID:Expression and characterization of the reverse transcriptase enzyme from type 1 human immunodeficiency virus using different baculoviral vector systems. 857 39

When given in standard dosages to treat bacterial respiratory and urinary tract infections, trimethoprim-sulfamethoxazole (TMP-SMX) is not commonly associated with hyperkalemia. However, the emergence of the acquired immunodeficiency syndrome has led to increased numbers of patients with Pneumocystis carinii pneumonia (PCP) who require high-dose TMP-SMX therapy. A 25-year-old man with human immunodeficiency virus infection developed hyperkalemia while receiving high-dose TMP-SMX for PCP. His baseline serum potassium of 3.0 mEq/L, which increased to 4.2 mEq/L after potassium replacement therapy, rose to 6.9 mEq/L after 8 days of TMP-SMX. No other etiology was found for the hyperkalemia, and the disorder resolved when TMP-SMX was stopped. It recurred when the patient was rechallenged with high doses of TMP-SMX during a second treatment course for PCP. This case and a review of previous reports highlight the importance of monitoring serum potassium concentrations in patients receiving high-dose TMP-SMX.
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PMID:Hyperkalemia associated with high-dose trimethoprim-sulfamethoxazole in a patient with the acquired immunodeficiency syndrome. 860 91


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