Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Poxviruses are known to contain a large number of open reading frames, particularly near the termini of the viral genome, that are not required for growth in tissue culture. However, many of these gene products are believed to play important roles in determining the virulence of the virus by modulating the host immune response to the infection. Recently it has been shown that Shope fibroma virus encodes, within the terminal inverted repeats, a protein (T2) related to the cellular tumor necrosis factor receptor (TNFR) and which specifically binds both TNF alpha and TNF beta. We have sequenced the terminal regions of two other Leporipoxviruses (myxoma virus and malignant rabbit fibroma virus) that are extremely invasive and capable of inducing extensive immunosuppression in rabbits and demonstrate that they also encode a closely related T2 homolog with all the structural motifs predicted for a secreted TNF binding protein. To investigate the biological role of the T2 protein, we have inactivated the myxoma virus T2 gene within each copy of the viral TIR by the insertion of a dominant selectable marker (Escherichia coli guanosine phosphoribosyltransferase) and selection of the recombinant virus in the presence of mycophenolic acid. The success of the inactivation of both copies of T2 was confirmed by the loss a broad protein band (52-56 kDa) of the predicted size for T2 from the profile of proteins secreted from mutant virus-infected BGMK cells at early times after infection. Although the T2-minus recombinant myxoma virus grew normally in tissue culture, upon infection of susceptible rabbits the viral disease was observed to be significantly attenuated. The majority of infected rabbits were able to mount an effective immune response to the infection and completely recovered. These survivor rabbits became immune to subsequent challenge with wild type myxoma virus. We conclude that the T2 viral protein is an important secreted virulence factor and that it in all likelihood functions by compromising the antiviral effects of TNF. We propose the term "viroceptor" to describe viral-encoded homologs of cellular lymphokine receptors whose function is to intercept the activity of the cognate lymphokine in order to short circuit the host immune response to the viral infection.
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PMID:Myxoma virus expresses a secreted protein with homology to the tumor necrosis factor receptor gene family that contributes to viral virulence. 165 97

A human T-T hybridoma clone with helper cell phenotype was established from fusions between a HPRT- variant of the human T-cell lymphoma Molt4, and PPD-activated normal human T-lymphocytes. The hybrid clone (MP-6) was characterized with regard to expression of markers and lymphokine secretion. The T-T hybridoma was positive for Leu 3a, and thus of T-helper cell lineage. The transferrin receptor (T-9) and the interleukin 2 (IL-2) receptor (Tac) were also expressed as judged by immunofluorescence analysis using monoclonal antibodies. The hybridoma produces B-cell stimulatory factor (BSF) with proliferation and maturation activities, growth inhibitory factor (GIF), leukocyte migration inhibitory factor (LIF) constitutively under serum free conditions, but no detectable interferons (IFN-alpha, IFN-beta, IFN-delta), nor interleukin 2 (IL-2). Weak interleukin 1 (IL-1)-like activity was found. The B-cell stimulatory factor (BSF) induced solid phase-anti-mu triggered resting B-cells obtained from human spleen, tonsil or peripheral blood to proliferate and to secrete IgM and IgG. Without anti-mu triggering the BSF had no proliferation inducing effect. The BSF was characterized and partially purified using ammonium sulphate precipitation, Blue-Sepharose, HPLC hydrophobic interaction and HPLC gel filtration chromatography. The BSF was heat labile at 56 degrees C and was present in two forms, one with high and one with intermediate hydrophobicity. The more hydrophobic form of BSF has a molecular weight of 12K-14K. Kinetic studies of the lymphokine secretion revealed that BSF was produced in detectable amounts in low density (0, 2 X 10(6) cells/ml) 18-24 h cultures. In 48 h to 72 h cultures there was a significant influence of growth inhibitory activities (GIF) produced. GIF, with an apparent MW of 90K could be absorbed out on certain tumor cell lines or on Blue-Sepharose. Further absorption analysis of BSF activities show that anti-mu triggered B-cells but neither resting B-cells nor T-cells could absorb BSF activity.
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PMID:A T-helper cell x Molt4 human hybridoma constitutively producing B-cell stimulatory and inhibitory factors. 294 47