Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A total of 40 multiple sclerosis (MS) patients from Denmark and 10 from the Faroes were examined for antibodies with affinity to human T cell leukemia/lymphoma virus type 1 (HTLV-I) and human immunodeficiency virus type 1 and 2 (HIV-1 and HIV-2). Using ELISA, MS patients and a group of healthy controls did not differ significantly in their reactivities to HTLV-I. However, elevated reactivities were recorded with 5 MS sera, whereas only 2 of the sera from the controls produced highly values. Ten patients with other neurological diseases all seemed to exhibit low reactivity in HTLV-I ELISA. The reactivities of 2 MS sera decreased considerably by absorption with an HTLV-I lysate. In immunofluorescence assay, two other MS sera reacted with HTLV-I transformed cell lines as well as with non-infected cells. Examined by Western blotting (WB), a single MS serum produced a distinct HTLV-I p19 band. With ELISA for detection of HIV-1 and HIV-2 antibodies, 2 MS sera exhibited borderline reactions. Further examination of these two sera by WB revealed weak reactivities against p24 and p53 of HIV-1. One the whole, the present observations do not suggest that a putative MS retrovirus would be closely related with HTLV-I, HIV-1 or HIV-2.
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PMID:Seroreactivity to human T cell leukemia/lymphoma virus type 1 and related retroviruses in multiple sclerosis patients from Denmark and the Faroes. 132 31

To determine seropositivity for human T-lymphotropic virus type I (HTLV-I), we attempted to improve the detection system that uses antibody to HTLV-I Env in Western immunoblotting (WB) by adding an envelope glycoprotein (gp46) purified from the culture fluid of HTLV-I-producing cells by immunoaffinity chromatography and gel chromatography. In this WB, 177 of 179 serum samples showing seropositivity in an indirect immunofluorescence assay showed positive reactions to the gp46 envelope antigen as well as to p19, p24, and p53 Gag antigens. The remaining two samples showed negative reactions to p24. False-positive results were not found for 533 indirect immunofluorescence assay-negative serum samples, although one band to p19 or p24 was observed in 46 of the 533 samples. These 46 samples did not react to p53 and gp46, suggesting that these samples belonged to the indeterminate group in accordance with the criteria proposed by the World Health Organization. Therefore, this improved WB can be used for the confirmation of seropositivity.
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PMID:Improvement of simultaneous detection of antibodies to Gag and envelope antigens of human T-lymphotropic virus type I by western immunoblot assay. 140 Sep 53

Two T-cell lines were established from peripheral blood mononuclear cells of two Moroccan patients with tropical spastic paraparesis and then named PR52 and PR144. The two cell lines showed a T lineage of activated CD4+ with high density of Tac+ (IL2 receptor). No expression of CD8 was observed. The virus particles were detected by reverse transcriptase activity and the viral antigens were also detected by immunofluorescence (IF) and Western blot. After six months of culture greater than 90% of the cells exhibited HTLVI antigen by IF. Lysate virus particles on Western blot analysis revealed p19,p24, and p53 gag protein similar to those detected in C91/PL virus particles from an adult T-cell leukemia (ATL) patient. gp46 and gp61 were also weakly detected. These two T-cell lines established will serve as substrate for further comparative studies on TSP and ATL isolates.
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PMID:Establishment of T-lymphoid cell lines from Morroccan patients with tropical spastic paraparesis. 152 May 34

A human T-cell line producing human T-cell leukemia virus type I (HTLV-I), MT-2, was injected intravenously into female F344 rats aged 5 weeks to make HTLV-I carrier rats. Antibody against HTLV-I was detected at the 5th week after MT-2 injection, and its titer reached a high plateau which continued from the 15th to the 27th week. The antibodies were against p19, p24, p28 and p53 of HTLV-I antigens from MT-2 cells. The gag, pX and LTR nucleotide sequences of HTLV-I provirus were demonstrated by using polymerase chain reaction (PCR) in the peripheral-blood mononuclear cells of 3 rats at the 44th week and 2 at the 66th to 68th week out of 8 F344 rats injected with MT-2 cells. Quantification of the HTLV-I proviral sequence revealed that 30 to 60 molecules were present in 10(5) peripheral-blood mononuclear cells, indicating that the rats were chronically infected with HTLV-I. HTLV-I-infected rats could serve as a small-animal model for studying the pathophysiological state of HTLV-I carriers and also that of HTLV-I infection on various HTLV-I-related diseases, including adult T-cell leukemia and HTLV-I-associated myelopathy.
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PMID:Infection of rats with HTLV-1: a small-animal model for HTLV-1 carriers. 168 81

Human T-cell leukemia virus type I (HTLV-I) protease has been purified to homogeneity from a strain of recombinant Escherichia coli. The protease was expressed as a larger precursor, which was autoprocessed to form a mature protease. Protein chemical analyses revealed the coding sequence of mature protease, which agreed with the putative sequence predicted from the sequence of bovine leukemia virus protease. The purified protease processed the natural substrate gag precursor (p53) to form gag p19 and gag p24. The protease activity was inhibited by pepstatin A. These results provide direct evidence that this protease belongs to the aspartic protease family and has an activity consistent with the protease in HTLV-I virion.
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PMID:Purification and characterization of human T-cell leukemia virus type I protease produced in Escherichia coli. 195 38

To explore the HTLV-I-carrying groups among the indigenous inhabitants in South America, a sero-epidemiological study on HTLV-I focusing on hinterland villages isolated from others in the Andes and Amazon regions was conducted. Five (2.9%) out of 171 subjects showed positive for HTLV-I antibody in the gelatin particle agglutination (PA) test. Two out of 5 positives with high antibody titer (greater than or equal to x 1024) in the PA test also showed a positive immunofluorescence (IF) test and anti-HTLV-I-specific protein products, p19, p24, p28, gp46, and p53 in sera by the Western blotting (WB) test. One of three negatives in the IF test showed positive antibodies to p19 and p24 by the WB test. Finally, two were confirmed as HTLV-I carriers and one was suspected of being a carrier. All three are Paez Indians from the central Andes; 53- and 34-year-old women and a 35-year-old man. The results show that HTLV-I carriers exist among isolated indigenous people in South America.
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PMID:Antibody to HTLV-I in indigenous inhabitants of the Andes and Amazon regions in Colombia. 197 4

We report three Texas-born patients with spastic paraparesis and well-documented infection with HTLV-I. CSF examination showed moderate pleocytosis, protein elevation, and elevated IgG index. Oligoclonal bands were present in two patients. On MRI, one patient had frontal lobe lesions that were low intensity on T1- and high intensity on T2-weighted images. HTLV-I immunoblot studies of serum and CSF revealed reactivity to p19, p24, p53, gp46, or gp68 from all three patients. Titration studies of serum and CSF antibodies on ELISA and immunoblot assays indicated an intrathecal virus-specific response. HTLV-I-specific p19 antigen capture assay and polymerase chain reaction (PCR) demonstrated HTLV-I in lymphocyte cultures derived from each patient's peripheral blood mononuclear cells (PBMC) or CSF cells. Using HTLV-I- and HTLV-II-specific pol and gag primers, PCR studies of PBMC cells obtained directly from the patients demonstrated that the patients were infected with HTLV-I and not HTLV-II. These three cases are to our knowledge the only US cases in whom virus isolation from the CSF has been accomplished. Importantly, two patients may be the first US cases of myelopathy arising from endemic infection.
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PMID:HTLV-I-associated myelopathy endemic in Texas-born residents and isolation of virus from CSF cells. 204 26

Twelve long-term cell lines were established from peripheral blood mononuclear cells (PBMC) or cerebrospinal fluid cells of patients with human T lymphotropic virus type I (HTLV-1) seropositive tropical spastic paraparesis (TSP) originating from the French West Indies, French Guyana or the Central African Republic. Most of these long-term interleukin-2-dependent cell lines exhibited a pattern characteristic of CD4(+)-activated T cells with high expression of CD2, CD3 and CD4 antigens, associated with a strong density of TAC and DR molecules. Nevertheless, in five cases CD8 expression was present at a significant level. HTLV-I antigens were never detected in uncultured PBMC, but they were expressed in a few cells after short-term culture and after 4 months the majority of the cells were HTLV-I positive, as demonstrated by indirect immunofluorescence (IF) using polyclonal or monoclonal anti-p19 and anti-p24 antibodies. Low and variable levels of reverse transcriptase activity were detected in supernatant fluids of these cell lines only after 4 months of culture, when at least 50% of the cells exhibited HTLV-I antigens by IF. However, numerous type C HTLV-I-like viral particles were detected, mostly in the extracellular spaces, with rare budding particles. Similar findings were found in three T cell lines derived from West Indian and African patients with adult T-cell leukaemia/lymphoma (ATLL). Differences in high Mr polypeptides were detected by Western blot in cell lysates when comparing TSP- or ATLL-derived T cell lines. Thus a signal of 62K was easily detectable in all the TSP lines, but not in the ATLL lines. In all cell lines bands corresponding to p53, p24 and p19 viral core polypeptides were present, as was the env gene-coded protein p46.
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PMID:Cell surface phenotype and human T lymphotropic virus type 1 antigen expression in 12 T cell lines derived from peripheral blood and cerebrospinal fluid of West Indian, Guyanese and African patients with tropical spastic paraparesis. 230 64

In the HTLV-I seroscreening of blood donor sera by gelatin particle agglutination (PA), more than 50% (55.6%) of the PA-positive sera were negative by immunofluorescence assay (IF). However, when donors were divided into age groups, there were increasing numbers of IF-positive/PA-positive donors with age. Among the PA-positive donors in the 50-64 age group, 65.9% were IF-positive compared to 16.0% in the 16-19 age group. The serological specificities of the IF-negative/PA-positive specimens were tested by using a newly developed PA inhibition (PAI) test. The HTLV-I specificity of the PAI test was confirmed by the observation that agglutinations with anti-HTLV-I p19 and gp21 monoclonal antibodies as well as IF-positive sera were specifically inhibited with HTLV-I preparations or HTLV-I-positive cell extracts and not with HTLV-I-negative cell extracts. Sixty of the 104 specimens collected randomly from the IF-negative/PA-positive donors were PAI-positive. The majority (80%) of such PAI-positive sera showed more than two bands of HTLV-I gag-encoded polypeptide, p19, p24, p28 and p53 on Western blotting. Some of the PAI-positive sera were also positive by enzyme immunoassay. These results indicate that at least some of the IF-negative/PA-positive donors possess HTLV-I-specific antibody and may be potential HTLV-I carriers who will become IF-positive at a later age.
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PMID:Evaluation of the human T-cell leukemia virus type I seropositivity of blood donors by the particle agglutination inhibition test. 251

The full-length provirus of human T-cell leukemia virus type I (HTLV-I) was isolated from MT-2, a lymphoid cell line producing HTLV-I. In transfected cells, structural proteins of HTLV-I, the gag and env products, were formed and processed in the same manner as observed in MT-2 cells. The nucleotide sequence was determined for a region between the gag and pol genes of the proviral DNA clone containing an open-reading frame. The deduced amino acid sequences show that this open-reading frame encodes a putative HTLV-I protease. The protease gene (pro) of HTLV-I was investigated using a vaccinia virus expression vector. Processing of 53k gag precursor polyprotein into mature p19, p24, and p15 gag structural proteins was detectable with a recombinant plasmid harboring the entire gag- and protease-coding sequence. We demonstrated that the protease processed the gag precursor polyprotein in a trans-action. A change in the sequence Asp(64)-Thr-Gly, the catalytic core sequence among aspartyl proteases, to Gly-Thr-Gly was shown to abolish correct processing, suggesting that HTLV-I protease may belong to the aspartyl protease group. The 76k gag-pro precursor polyprotein was identified, implying that a cis-acting function of HTLV-I protease may be necessary to trigger the initial cleavage event for its own release from a precursor protein, followed by the release of p53 gag precursor protein. The p53 gag precursor protein is then processed by the trans-action of the released protease to form p19, p24, and p15.
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PMID:Identification of HTLV-I gag protease and its sequential processing of the gag gene product. 266 87


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