Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tax gene product (Tax protein) of human T-cell leukemia virus type I (HTLV-I) is a specific transcriptional activator of the viral long terminal repeat sequence and is essential for the replication cycle of the virus. To elucidate the relationship between the presence of anti-Tax antibody and the transmission of the viral infection, annual consecutive serum samples from married couples serologically discordant or concordant for HTLV-I were examined. These included 5 individuals whose spouses seroconverted during this 5-year follow-up study period. The samples were tested by a Western blot assay using a recombinant Tax protein as the antigen. The results showed that 24 of 32 (75%) men in the concordant couples (both husband and wife were HTLV-I carriers) had anti-Tax antibody, while only 5 of 18 (27.8%) men in the discordant couples (husband was carrier and wife was seronegative to HTLV-I) were positive for anti-Tax antibody (P = 0.0012). Furthermore, all spouses of the 5 seroconverters (4 women and 1 man) had anti-Tax antibody, while only 23 of 46 (50%) age-matched randomly selected HTLV-I carriers from the discordant-couple group had anti-Tax antibody. When the data were analyzed by gender, all husbands of the female seroconverters had anti-Tax antibodies, which was significantly higher than the prevalence of anti-Tax antibodies in men who did not transmit the virus to their spouses during the follow-up period (P = 0.017). In addition, antibody reactivity to other HTLV-I antigens (including Env gp46, transmembrane protein gp21, and Gag p19 and p24) were examined. The results indicated no significant differences between the prevalence of antibody reactivity to any of the antigens in the spouses of the seroconverters and the reference group. We conclude that the presence of anti-Tax antibody in men may indicate a high risk of viral transmission to their wives via heterosexual routes.
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PMID:Sexual transmission of human T-cell leukemia virus type I associated with the presence of anti-Tax antibody. 199 21

A series of synthetic peptides derived from the corresponding regions of the gag, pol, and env proteins of human T-cell lymphotropic virus types I (HTLV-I) and II (HTLV-II) were used in an enzyme immunoassay to map the immunodominant epitopes of HTLV. Serum specimens from 79 of 87 (91%) HTLV-I-infected patients reacted with the synthetic peptide Gag-1a (amino acids [a.a.] 102 to 117) derived from the C terminus of the p19gag protein of HTLV-I. Minimal cross-reactivity (11%) was observed with serum specimens from HTLV-II-infected patients. Peptide Pol-3, encoded by the pol region of HTLV-I (a.a. 487 to 502), reacted with serum specimens from both HTLV-I- and HTLV-II-infected patients (94 and 86%, respectively). The antibody levels to Pol-3 were significantly higher (P less than 0.01) in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis than in either adult T-cell leukemia patients or HTLV-I-positive asymptomatic carriers. None of the other peptides studied demonstrated significant binding to serum specimens obtained from HTLV-I- or HTLV-II-infected individuals. While Gag-1a did not react with serum specimens from normal controls, Pol-3 demonstrated some reaction with specimens from seronegative individuals (11.4%). The antibodies to Gag-1a and Pol-3 in serum specimens from HTLV-I-infected patients could be specifically inhibited by the corresponding synthetic peptides and by a crude HTLV-I antigen preparation, indicating that these peptides mimic native epitopes present in HTLV-I proteins that are recognized by serum antibodies from HTLV-I- and -II-infected individuals.
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PMID:Characterization of immunodominant epitopes of gag and pol gene-encoded proteins of human T-cell lymphotropic virus type I. 200 47

The pol gene of the Moloney murine leukemia virus (M-MuLV) is expressed as a Gag-Pol fusion protein through an in-frame suppression of the UAG termination codon located between the two genes. The role of nucleotide context in suppression was investigated, in a rabbit reticulocyte lysate translation system, using site-directed mutagenesis. The results indicate that the translational readthrough is mediated by at least 50 bases long RNA sequence located 3' to the gag UAG termination codon. Within this sequence a short purine-rich sequence adjacent to the amber codon, highly conserved among different retroviruses, appears essential for M-MuLV suppression. Two alternative putative stem and loop like RNA structures can be drawn at the gag-pol junction, one abutting the gag UAG codon, and the second downstream to it. None of these structures appears to be important to the suppression process.
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PMID:cis Acting RNA sequences control the gag-pol translation readthrough in murine leukemia virus. 205 84

The human T-cell leukemia virus type I rex gene product plays a critical role in the expression of the retroviral structural proteins Gag and Env from incompletely spliced mRNAs. Rex protein acts through a cis element (rex-response element [RxRE]) which is located in the U3/R region of the 3' long terminal repeat and is present on all human T-cell leukemia virus type I-specific mRNAs. Two domains of the predicted secondary structure of the RxRE are crucially important for Rex action in vivo as measured by two assay systems. In vitro studies using highly purified recombinant Rex protein revealed a specific and direct interaction with radiolabeled RxRE sequences. The correlation between our in vivo results and the direct binding of Rex protein to mutant and wild-type RxRE sequences supports both the existence of the predicted secondary structure and the importance of this direct interaction with the cis-acting RNA sequence for Rex function in vivo.
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PMID:Functional analysis of human T-cell leukemia virus type I rex-response element: direct RNA binding of Rex protein correlates with in vivo activity. 207 57

Visna virus is an ungulate lentivirus that is distantly related to the primate lentiviruses, including human immunodeficiency virus type 1 (HIV-1). Replication of HIV-1 and of other complex primate retroviruses, including human T-cell leukemia virus type I (HTLV-I), requires the expression in trans of a virally encoded post-transcriptional activator of viral structural gene expression termed Rev (HIV-1) or Rex (HTLV-I). We demonstrate that the previously defined L open reading frame of visna virus encodes a protein, here termed Rev-V, that is required for the cytoplasmic expression of the incompletely spliced RNA that encodes the viral envelope protein. Transactivation by Rev-V was shown to require a cis-acting target sequence that coincides with a predicted RNA secondary structure located within the visna virus env gene. However, Rev-V was unable to function by using the structurally similar RNA target sequences previously defined for Rev or Rex and, therefore, displays a distinct sequence specificity. Remarkably, substitution of this visna virus target sequence in place of the HIV-1 Rev response element permitted the Rev-V protein to efficiently rescue the expression of HIV-1 structural proteins, including Gag, from a Rev- proviral clone. These results suggest that the post-transcriptional regulation of viral structural gene expression may be a characteristic feature of complex retroviruses.
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PMID:Visna virus encodes a post-transcriptional regulator of viral structural gene expression. 217 Sep 81

Myristoylation of the Pr65gag protein from Moloney murine leukemia virus has been shown to be essential for virus particle formation [Rein et al., Proc. Natl. Acad. Sci. USA 83 (1986) 7246-7250], and by analogy, myristoylation of the human immunodeficiency virus (HIV) Gag precursor could possibly play a similar role. We have investigated the expression and myristoylation of the complete HIV Gag precursor Pr55gag in yeast, the subcellular localization of that protein, and the contribution of the myristoyl-glycine residue to this localization. Immunogold labelling of myristoylated Pr55gage with antibodies directed against HIV Gag products was apparent in the vicinity of the plasma membrane. On the contrary, non-myristoylated derivatives of Pr55gag were only detected in relatively well-defined regions of the cytoplasm. These results show that targeting and accumulation of the HIV Gag precursor, Pr55gag, at the plasma membrane occurs in yeast in the absence of other viral components and requires the N-myristoyl-glycine residue.
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PMID:The HIV-1 Gag precursor Pr55gag synthesized in yeast is myristoylated and targeted to the plasma membrane. 267 35

The env-pX IV fused gene of human T-cell leukemia virus type I (HTLV-I) was inserted into lac promoter-directed expression vectors for production of viral proteins in bacteria. Resulting recombinant plasmids, pK13 and pK15, directed synthesis of fused proteins of 59 kDa (Env-p40x) and 100 kDa (Gag-Env-p40x), respectively. Western blot analysis showed that these proteins were reactive with sera of patients with adult T-cell leukemia (ATL) and retained multiple antigenic determinants of viral proteins. In combination with recombinant Gag protein [S. Itamura, K. Shigesada, M. Imai, N. Kobayashi, T. Hamakado, T. Harada and M. Hatanaka, Gene 38, 57-64 (1985)], these bacterially synthesized proteins may provide a useful tool for differential diagnosis of ATL by detecting serum antibodies against individual viral proteins and for analysis of viral gene functions.
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PMID:Synthesis of proteins in Escherichia coli immunoreactive with sera from individuals infected with human T-cell leukemia virus type I. 289 99

An expression plasmid, pHY202, was constructed which directs the synthesis of a fusion protein encoded by the gag sequence of human T-cell leukemia virus type I (HTLV-I) inserted into the lacZ' gene. Escherichia coli cells harboring pHY202 produced the 43-kDal LacZ'-Gag fusion protein with a yield of approx. 0.3% of total soluble proteins. The fusion protein is specifically recognized by monoclonal antibodies against the Gag proteins p19 and p24, and could be applicable for the diagnosis of HTLV-I infection, because almost all sera from HTLV-I carriers gave a positive response in the enzyme-linked immunosorbent assay (ELISA) employing the LacZ'-Gag hybrid protein purified by immunoaffinity column chromatography.
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PMID:Expression of the gag gene of human T-cell leukemia virus type I in Escherichia coli and its diagnostic use. 299 50

Efficient expression of human T-cell leukemia virus (HTLV) and human immunodeficiency virus structural proteins requires Rx and Rev proteins, respectively. Decreased expression of Gag and Env appears to be due, in part, to intragenic RNA sequences, termed cis-acting repressive sequences (CRS), and may be mediated by binding of specific cellular factors. We demonstrated previously that two cellular proteins, p60CRS and p40CRS, interact with HTLV type 2.5' long terminal repeat CRS RNA and that the interaction of both proteins with CRS RNA correlates with function (A. C. Black, C. T. Ruland, J. Luo, A. Bakker, J. K. Fraser, and J. D. Rosenblatt, Virology 200:29-41, 1994). By radioimmunoprecipitation of HeLa nuclear proteins UV cross-linked to CRS RNAs with murine monoclonal antibodies, we now show that p40CRS is heterogeneous nuclear ribonucleoprotein (hnRNP) A1 and p60CRS is polypyrimidine tract-binding protein or hnRNP I. These immunoprecipitation results were confirmed by an immunobinding assay with hnRNP I and hnRNP AI antibodies and by cross-competition electrophoretic mobility shift experiments. In addition, we mapped a putative hnRNP A1 binding site in U5 RNA and demonstrated that p40CRS (hnRNP A1) binding to that site correlates with CRS function. Since both hnRNP I and hnRNP A1 have been shown to influence splicing and potentially other steps in RNA processing, the binding of both hnRNP I and hnRNP A1 to HTLV RNA regulatory elements may alter retrovirus RNA processing and may be involved in regulation by Rex.
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PMID:Polypyrimidine tract-binding protein and heterogeneous nuclear ribonucleoprotein A1 bind to human T-cell leukemia virus type 2 RNA regulatory elements. 747 99

A study of simian T-cell leukemia virus type 1 (STLV-1) infection in a captive colony of 23 Macaca tonkeana macaques indicated that 17 animals had high human T-cell leukemia virus type 1 (HTLV-1) antibody titers. Genealogical analysis suggested mainly a mother-to-offspring transmission of this STLV-1. Three long-term T-cell lines, established from peripheral blood mononuclear cell cultures from three STLV-1-seropositive monkeys, produced HTLV-1 Gag and Env antigens and retroviral particles. The first complete nucleotide sequence of an STLV-1 (9,025 bp), obtained for one of these isolates, indicated an overall genetic organization similar to that of HTLV-1 but with a nucleotide variability for the structural genes ranging from 7.8 to 13.1% compared with the HTLV-1 ATK and STLV-1 PTM3 Asian prototypes. The Tax and Rex regulatory proteins were well conserved, while the pX region, known to encode new proteins in HTLV-1 (open reading frames I and II), was more divergent than that in the ATK strain. Furthermore, a fragment of 522 bp of the gp21 env gene from uncultured peripheral blood mononuclear cell DNAs from five of the STLV-1-infected monkeys was sequenced. Phylogenetic trees constructed with the long terminal repeat and env (gp46 and gp21) regions demonstrated that this new STLV-1 occupies a unique position within the Asian STLV-1 and HTLV-1 isolates, being, by most analyses, related more to the Australo-Melanesian HTLV-1 topotype than to any other Asian STLV-1. These data raise new hypotheses on the possible interspecies viral transmission between monkeys carrying STLV-1 and early Australoid settlers, ancestors of the present day Australo-Melanesian inhabitants, during their migrations from the Southeast Asian land mass to the greater Australian continent.
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PMID:Isolation and characterization of a new simian T-cell leukemia virus type 1 from naturally infected celebes macaques (Macaca tonkeana): complete nucleotide sequence and phylogenetic relationship with the Australo-Melanesian human T-cell leukemia virus type 1. 747 17


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