UNIPROT:P01034 - FACTA Search

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Query: UNIPROT:P01034 (cystatin C)
3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A solid-phase enzyme-linked immunosorbent assay (ELISA) for determining human serum cystatin C is described. In 50 normal samples, cystatin C concentration was 1247 +/- 224 micrograms/L (mean +/- SD) which is in agreement with previously reported levels. Serum levels of cystatin C and beta 2-microglobulin (beta 2-M) were investigated in a time-course study during the development of human immunodeficiency virus (HIV) infection. We found a persistent and uniform increase in the beta 2-M concentration (2762 +/- 1239 micrograms/L). In contrast to beta 2-M, on the basis of cystatin C levels, we found two distinct populations, one of which demonstrated an increased concentration (1620 +/- 618 micrograms/L). Interestingly a second group (21% of patients) exhibited an initial significant decrease in cystatin C concentration with a mean value of 377 (range 55-850) micrograms/L, followed by an increase. The biphasic pattern of cystatin C serum, a major cysteine proteinase inhibitor, during the course of HIV infection suggests a possible role for these proteinases (or proteinase inhibitors) in the development of this syndrome.
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PMID:Cystatin C levels in sera of patients with human immunodeficiency virus infection. A new avidin-biotin ELISA assay for its measurement. 156 12

Mammalian cells contain two species of glutamine tRNAs, tRNA(CUGGIn) and tRNA(UmUGGIn). The later minor glutamine tRNA which has the UmUG anticodon sequence can recognize an UAG amber termination codon of natural mRNA in an in vitro translation system. Recognition of the UAG nonsense codon by mammalian tRNA(UmUGGIn) is facilitated by two wobble base-pairs at the first and third position of the anticodon. Such unorthodox interaction between the codon and the anticodon which is not in accordance with the wobble hypothesis or the two out of three reading mechanism has been shown only in the recognition of the UAG nonsense codon by natural suppressor tRNA such as yeast tRNA(SGIn) and bovine liver tRNA(CAGLeu). Due to such unique interaction with mRNA, the suppressor activity of mammalian glutamine tRNA(UmUGGIn) is weaker than that of tobacco tRNA(G psi ATyr), which is known to be a natural UAG suppressor tRNA in plants. Retrovirus infection followed by vegetative growth causes the selective and remarkable increase of the amount of UAG suppressor glutamine tRNA(UmUGGIn) in the virus-infected cells. The increased amount of tRNA(UmUGGIn) seems to be important not only for the sufficient production of a viral UAG readthrough protein, but also for the efficient translation of viral mRNAs, since tRNA(UmUGGIn) should read as efficiently the CAA glutamine codon which frequently appears in the viral genome. The increased level of tRNA(UmUGGIn) in virus-infected cells might be due to specific transcription activation of the tRNA gene for tRNA(UmUGGIn). The factor required for the transcription regulation of the suppressor tRNA gene, if it exists in virus infected cells, may not be the same as the factors TFIIIB, IIIC and IIID so far identified. If such a specific transcription factor exists, it would be interesting to characterize it and to elucidate the mechanism by which it is induced by infection with Mo-MuLV or HIV.
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PMID:[Natural UAG suppressor glutamine tRNA in retrovirus infected cells]. 253 81

Foscarnet (phosphonoformic acid) is a pyrophosphate analog that inhibits the replication of human immunodeficiency virus type 1 (HIV-1) in vitro and in patients with AIDS. HIV-1 resistance to foscarnet has not been reported despite long-term foscarnet therapy of AIDS patients with cytomegalovirus disease. We therefore attempted to select foscarnet-resistant HIV-1 in vitro by serial endpoint passage of virus in 400 microM foscarnet. After 13 cycles of passage in MT-2 cells, virus exhibiting > or = 8.5-fold foscarnet resistance was isolated. The reverse transcriptase (RT) from resistant virions exhibited a similar level of foscarnet resistance in enzyme inhibition assays (approximately 10-fold resistance). Foscarnet-resistant virus showed increased susceptibility to 3'-azido-3'-deoxythymidine (90-fold) and to the HIV-1-specific RT inhibitors TIBO R82150 (30-fold) and nevirapine (20-fold). DNA sequence analysis of RT clones from resistant virus revealed the coexistence of two mutations in all clones: Gln-161 to Leu (CAA to CTA) and His-208 to Tyr (CAT to TAT). Sequence analysis of six clinical HIV-1 isolates showing reduced susceptibility to foscarnet revealed the Tyr-208 mutation in two, the Leu-161 mutation in one, and a Trp-88-to-Ser or -Gly mutation in four isolates. Site-specific mutagenesis and production of mutant recombinant viruses demonstrated that the Leu-161, Ser-88, and Tyr-208 mutations reduced HIV-1 susceptibility to foscarnet 10.5-, 4.3-, and 2.4-fold, respectively, in MT-2 cells. In the crystal structure of HIV-1 RT, the Gln-161 residue lies in the alpha E helix beneath the putative deoxynucleoside triphosphate (dNTP) binding site. The Gln-161-to-Leu mutation may affect the structure of the dNTP binding site and its affinity for foscarnet. The location of the Trp-88 residue in the Beta5a strand of HIV-1 RT suggest that the Ser-88 mutation affects template-primer binding, as do several mutations that affect RT susceptibility to nucleoside analogs.
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PMID:Novel mutations in reverse transcriptase of human immunodeficiency virus type 1 reduce susceptibility to foscarnet in laboratory and clinical isolates. 754 60

To determine whether human immunodeficiency virus (HIV) infection is associated with incipient tubular or glomerular defects, we determined the urinary excretion of four low molecular weight proteins (LMWP); beta2-microglobulin (U-beta2-m), cystatin C (U-cyst C), Clara cell protein (U-CC16), and retinol-binding protein (U-RBP), the markers of tubular dysfunction, the excretion of albumin (U-Alb), a marker of glomerular defect, and the excretion of N-acetyl-beta-D-glucosaminidase (U-NAG), a marker of structural damage of the proximal tubular epithelium. Their determinants have been assessed by stepwise regression analysis using as possible predictors age, sex, serum-beta2-m (S-beta2-m), CD4 lymphocyte count, or HIV infection stage and therapy. The study involved 76 HIV-infected patients without renal disease, 56 with S-beta2-m < 5 mg/L (Group B1), 20 with S-beta2-m > or = 5 mg/L (Group B2), and 30 HIV-negative controls. Fourteen patients (18.4%) had no abnormal urinary protein loss, and 62 (81.6%) had elevated urinary excretion of at least one protein (Alb, LMWP, or NAG). A single urinary protein was abnormal in 21 patients (U-beta2-m, n = 9; U-RBP, n = 2; U-CC16, n = 4; and U-Alb, n = 6). At least two LMWP were abnormal without increased U-Alb in 23 patients (12 with increased and 11 with normal U-NAG). Ten patients had an increased urinary excretion of at least one LMWP together with U-Alb (5 with increased and 5 with normal U-NAG). An increased urinary excretion of all proteins was observed in the last 8 patients. The average urinary excretion of all proteins (except cyst C) was significantly higher in HIV than in the control group. As expected, U-beta2-m and the prevalence of abnormal U-beta2-m values were higher in the B2 than in the B1 group (P = 0.0001), whereas the average urinary excretion and the prevalence of elevated values of Alb, LMWP (except beta2-m) or NAG were the same in both HIV groups. By stepwise regression analysis, age emerged as a significant determinant of urinary excretion of beta2-m and CC16, whereas male sex was associated with increased U-CC16. S-beta2-m, CD4-lymphocyte count, or HIV infection stage emerged as significant determinants only for U-beta2-m as a consequence of a close correlation between S-beta2-m and either HIV infection stage (r = -0.52, P = 0.0001), or CD4 count (r = -0.45, P = 0.0002). Over 80% of HIV-infected patients without overt renal disease have evidence of glomerular permeability defects or tubular dysfunction, whatever the stage of the disease. U-Alb, RBP, and CC16 appear as the most sensitive and reliable early markers of these abnormalities. Their cause and prognostic value remain to be determined.
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PMID:Low molecular weight proteinuria in human immunodeficiency virus-infected patients. 865 Dec 44

We have recently reported the isolation and molecular cloning of a human immunodeficiency virus type 1 isolate (HIV-1 DH125) that exhibits rapid replication kinetics and marked cytopathicity in both human and chimpanzee peripheral blood mononuclear cells (PBMC). To identify the viral determinants responsible for infectivity of chimpanzee PBMC, chimeric viruses containing the following components were constructed: (i) the entire envelope gene; (ii) gp120 sequences; (iii) gp41 sequences; and (iv) individual or various combinations of the gp120 variable regions of HIV-1 DH125 inserted into the backbone of another HIV-1 isolate (HIV-1 AD8), which is unable to infect chimpanzee PBMC. Analyses of virus replication kinetics in human and chimpanzee PBMC revealed that gp120 contains determinants which confer infectivity for chimpanzee PBMC and that the capacity to establish such an infection requires the cooperative interaction between multiple variable regions of the HIV-1 DH125 gp120.
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PMID:Infection of chimpanzee peripheral blood mononuclear cells by human immunodeficiency virus type 1 requires cooperative interaction between multiple variable regions of gp120. 879 90

The chemokine receptors CCR5 and CXCR4, in combination with CD4, mediate cellular entry of macrophage-tropic (M-tropic) and T-cell-tropic strains of human immunodeficiency virus type 1 (HIV-1), respectively, while dualtropic viruses can use either receptor. We have constructed a panel of chimeric viruses and envelope glycoproteins in which various domains of the dualtropic HIV-1(DH12) gp160 were introduced into the genetic background of an M-tropic HIV-1 isolate, HIV-1(AD8). These constructs were employed in cell fusion and virus infectivity assays using peripheral blood mononuclear cells, MT4 T cells, primary monocyte-derived macrophages, or HOS-CD4 cell lines, expressing various chemokine receptors, to assess the contributions of different gp120 subdomains in coreceptor usage and cellular tropism. As expected, the dualtropic HIV-1(DH12) gp120 utilized either CCR3, CCR5, or CXCR4, whereas HIV-1(AD8) gp120 was able to use only CCR3 or CCR5. We found that either the V1/V2 or the V3 region of HIV-1(DH12) gp120 individually conferred on HIV-1(AD8) the ability to use CXCR4, while the combination of both the V1/V2 and V3 regions increased the efficiency of CXCR4 use. In addition, while the V4 or the V5 region of HIV-1(DH12) gp120 failed to confer the capacity to utilize CXCR4 on HIV-1(AD8), these regions were required in conjunction with regions V1 to V3 of HIV-1(DH12) gp120 for efficient utilization of CXCR4. Comparison of virus infectivity analyses with various cell types and cell fusion assays revealed assay-dependent discrepancies and indicated that events occurring at the cell surface during infection are complex and cannot always be predicted by any one assay.
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PMID:Identification of determinants on a dualtropic human immunodeficiency virus type 1 envelope glycoprotein that confer usage of CXCR4. 949 15

Changes in neutralizing antibody (NA) titers in stored sera collected over 5 years from 10 participants in the Multicenter AIDS Cohort Study (MACS) were evaluated. The participants were HIV-1 infected on enrollment in the MACS, and remained AIDS free during the 5-year study interval. Seven viruses derived from molecular clones were used in NA assays; five of the viruses were T tropic (NL4-3, ALA1, NY5, SF2, and Z2Z6) and two were M tropic [AD8 and NL(SF162)]. In addition, pseudoviruses (PVs) were constructed that expressed envelope genes from NL4-3, ALA1, AD8, and SF162 and from primary viruses from two MACS participants (PV-9 and PV-10). There was significant correlation between NA titers obtained in four of five virus/PV comparisons, while the SF162 PV was more sensitive to NA than the corresponding virus. Comparable changes in NA titers were detected using viruses and PVs. Fourfold or greater increases in NA titers were noted in each of the participants, involving recognition of one to five of the nine strains tested. In some patients these NA titer changes appeared as discrete episodes of immune responses, while in others there may have been either multiple episodes or continuous evolution of the NA responses. The data indicate that changes in NA specificity occur during HIV-1 infection, which may result from the occurrence of neutralization escape mutation. The use of PVs for the study of phenotypic characteristics of envelope glycoproteins should facilitate the study of neutralization escape mutation in HIV-1 infection.
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PMID:Evolution of neutralizing antibody response against HIV type 1 virions and pseudovirions in multicenter AIDS cohort study participants. 968 40

The human immunodeficiency virus type 1 (HIV-1) Vpu and Env proteins are expressed from a bicistronic mRNA. To address the biological significance of the coordinated expression of vpu and env, we compared the relative effects on particle release of HIV-1 isolates containing an intact vpu gene or carrying point mutations in its initiation codon or internal deletions, respectively. We found that the primary AD8 isolate, which is unable to express vpu due to a mutation in its translation initiation codon, was able to replicate in primary macrophages and peripheral blood mononuclear cells with efficiency similar to that of an isogenic variant expressing Vpu. Interestingly, AD8 lacking a vpu initiation codon produced higher levels of Env protein than its Vpu-expressing isogenic variant. In contrast, disabling Vpu without removing the vpu initiation codon did not alter Env expression but significantly reduced virus production. AD8 Env when provided in trans was capable of enhancing release not only of AD8 particles but also of viruses of the T-cell-tropic NL4-3 isolate. We conclude that AD8 Env encodes a Vpu-like activity similar to that previously reported for HIV-2 Env proteins and is thus able to augment virus secretion. When expressed at elevated levels, i.e., following mutation of the vpu initiation codon, AD8 Env was able to compensate for the lack of Vpu and thereby ensure efficient virus release. Thus, the ability to regulate virus release is redundant in AD8 and can be controlled by either Vpu or Env. Since Vpu controls several independent functions, including CD4 degradation, our results suggest that some HIV-1 isolates may have evolved a mechanism to regulate Vpu activity without compromising their ability to efficiently replicate in the host cells.
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PMID:Regulation of virus release by the macrophage-tropic human immunodeficiency virus type 1 AD8 isolate is redundant and can be controlled by either Vpu or Env. 988 89

The envelope glycoprotein of human immunodeficiency virus 1 (HIV-1) plays important roles in viral life cycle and pathogenesis. Understanding the immune responses the protein elicits during the course of a viral infection in patients is important in designing an effective vaccine candidate against the virus or for better diagnosis of the disease. In this study, we report that gp120 of R5 isolates have higher Western blot (WB) immunoreactivity to antibodies elicited against the protein in virus-infected human patients compared with that of X4 and X4R5 isolates. Analyses of WB immunoreactivity of chimeric gp120s constructed between R5 (AD8) and X4R5 (DH12) HIV-1 isolates indicate that there are complex tertiary interdomain interactions even after a complete denaturation of the protein. Our data suggest that the determinant(s) responsible for the high WB immunoreactivity might be present in all gp120s, but are accessible to antibodies only for R5 gp120s in the WB assay. The V1/V2 and/or V3 regions of X4 and X4R5 gp120s likely interfere with either the formation or surface exposure of the WB immunoreactive determinant. Supplementing HIV-1 WB diagnosis kits with purified R5 gp120 could improve their sensitivity and facilitate earlier diagnosis of virus infection.
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PMID:Higher western blot immunoreactivity of glycoprotein 120 from R5 HIV type 1 isolates compared with X4 and X4R5 isolates. 1082 83

The great difficulty in eliciting broadly cross-reactive neutralizing antibodies (NAbs) against human immunodeficiency virus type 1 (HIV-1) isolates has been attributed to several intrinsic properties of their viral envelope glycoprotein, including its complex quaternary structure, extensive glycosylation, and marked genetic variability. Most previously evaluated vaccine candidates have utilized envelope glycoprotein from a single virus isolate. Here we compare the breadth of NAb and protective immune response following vaccination of pigtailed macaques with envelope protein(s) derived from either single or multiple viral isolates. Animals were challenged with Simian/human immunodeficiency virus strain DH12 (SHIV(DH12)) following priming with recombinant vaccinia virus(es) expressing gp160(s) and boosting with gp120 protein(s) from (i) LAI, RF, 89.6, AD8, and Bal (Polyvalent); (ii) LAI, RF, 89.6, AD8, Bal, and DH12 (Polyvalent-DH12); (iii) 89.6 (Monovalent-89.6); and (iv) DH12 (Monovalent-DH12). Animals in the two polyvalent vaccine groups developed NAbs against more HIV-1 isolates than those in the two monovalent vaccine groups (P = 0.0054). However, the increased breadth of response was directed almost entirely against the vaccine strains. Resistance to SHIV(DH12) strongly correlated with the level of NAbs directed against the virus on the day of challenge (P = 0.0008). Accordingly, the animals in the Monovalent-DH12 and Polyvalent-DH12 vaccine groups were more resistant to the SHIV(DH12) challenge than the macaques immunized with preparations lacking a DH12 component (viz. Polyvalent and Monovalent-89.6) (P = 0.039). Despite the absence of any detectable NAb, animals in the Polyvalent vaccine group, but not those immunized with Monovalent-89.6, exhibited markedly lower levels of plasma virus than those in the control group, suggesting a superior cell-mediated immune response induced by the polyvalent vaccine.
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PMID:Polyvalent envelope glycoprotein vaccine elicits a broader neutralizing antibody response but is unable to provide sterilizing protection against heterologous Simian/human immunodeficiency virus infection in pigtailed macaques. 1116 Jul 26

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