Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ME26 virus, which was generated by inserting the coding region of the acute avian leukemia-inducing virus E26 into a murine retrovirus vector, encodes a 135-kDa gag-myb-ets fusion protein. Amphotropic murine leukemia virus pseudotypes of ME26 virus induce a high incidence of erythroleukemia 2 to 4 months after injection into newborn NFS/N mice. Spleen cells from the majority of these mice proliferate to high levels in the presence of the erythroid hormone erythropoietin (Epo) and can easily be established as permanent Epo-dependent cell lines. The cell lines contain multiple copies of ME26 viral DNA and express viral message and protein. An Epo receptor mRNA of normal size can be detected in these cells, and binding studies reveal a single class of lower-affinity Epo receptor with an affinity for Epo that is in the range of that previously reported for erythroid cells. The ME26 virus-induced Epo-dependent cell lines, however, appear more immature than previously described erythroid cell lines and more closely resemble early hematopoietic precursor cells, suggesting that the virus may be activating the Epo receptor in hematopoietic cells that do not normally express it. Consistent with this idea, we are able to infect an interleukin-3-dependent myeloid cell line, FDC-P2, with ME26 virus and convert it to Epo dependence. The ME26 virus-infected FDC-P2 cells, even before growth on Epo, showed a large increase in the amount of Epo receptor mRNA. However, no ME26 viral integrations can be detected adjacent to the Epo receptor gene, indicating that the virus is not activating the Epo receptor gene by promoter/enhancer insertion. Our results are more consistent with the hypothesis that the gag-myb-ets-encoded viral fusion protein, which is known to bind DNA, is directly or indirectly activating the expression of the Epo receptor gene in these cells.
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PMID:Induction of erythropoietin responsiveness in murine hematopoietic cells by the gag-myb-ets-containing ME26 virus. 130 43

T cell immune responses in syngeneic WKA/H rats were analyzed by using lymphoid cell lines, TARS-1, TART-1, and TARL-2, infected with human T-lymphotropic virus type 1 (HTLV-1). Spleen cells of rats in which these cell lines had been rejected were sensitized in vitro with the same cell lines, and cells cytotoxic to these HTLV-1+ cell lines, and cells cytotoxic to these HTLV-1+ cell lines were generated. The effector cells were CTL of the CD5+ CD8+ phenotype and showed restriction of MHC class I Ag. Direct tests as well as cold target cell inhibition tests with an array of cell populations showed that these CTL reacted only with syngeneic HTLV-1+ cell lines. When xenogeneic HTLV-1+ cell lines were similarly utilized for in vitro sensitization, rat CTL specific for syngeneic HTLV-1+ cells were generated. They were not, however, reactive with xenogeneic HTLV-1+ cells used for sensitization. Syngeneic rat cells selectively expressing gag, env, or pX gene coded Ag were prepared by infection of recombinant vaccinia viruses. In cold target cell inhibition tests of anti-HTLV-1 CTL with thus prepared cells, cytotoxicity against the syngeneic HTLV-1+ cells line, TARS-1, was inhibited by syngeneic cells expressing gag gene or env gene coded Ag. Inhibition was, however, more consistent and more dominant by cells with gag gene than those with env gene. Syngeneic cells with pX gene and MHC class I incompatible cells with gag, env, or pX gene did not inhibit cytotoxicity.
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PMID:Rat cytotoxic T lymphocytes against human T-lymphotropic virus type 1-infected cells recognize gag gene and env gene encoded antigens. 247 89

Previous studies in our laboratory and others have been consistent with the hypothesis that the envelope (env) gene of the spleen focus-forming virus (SFFV) is the only gene essential for the induction of acute erythroleukemia. However, no studies have been carried out with the SFFV env gene in the complete absence of other SFFV sequences. To accomplish this goal, we isolated the sequences that encode the envelope glycoprotein, gp52, of SFFVA and expressed them in a Moloney murine leukemia virus-based double-expression vector containing the neomycin resistance gene. The method used to produce retrovirus stocks in tissue culture cells affected the expression of the gp52 gene in the vector and the subsequent pathogenicity of the vector in mice. Highly pathogenic virus stocks were obtained by cotransfection of vector and helper virus DNAs into fibroblasts, followed by virus replication and spread through the cell population. Mice infected with this stock developed a rapid erythroid disease that was indistinguishable from that induced by the entire SFFV genome, and the virus stock transformed erythroid cells in vitro. Spleen cells from the diseased mice expressed the SFFV env gene product but not the SFFV gag gene product. As expected, mice given the virus containing the SFFV env gene in the reverse orientation did not express the SFFV env gene product or develop erythroleukemia. This study, therefore, demonstrated (i) that double-expression retroviral vectors can be used under specific conditions to produce viruses expressing high levels of a particular gene and (ii) that incorporation of the SFFV env gene into such a vector in the absence of other SFFV sequences results in a retrovirus which is as pathogenic as the original SFFV.
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PMID:The spleen focus-forming virus (SFFV) envelope gene, when introduced into mice in the absence of other SFFV genes, induces acute erythroleukemia. 283 16

Spleen cells from Rfv-3r/s mice with Friend virus-induced erythroleukemia were analyzed for expression of virus-induced proteins with monoclonal antiviral antibodies and conventional antisera. Leukemic spleen cells, 30-60 d after virus inoculation, expressed decreased amounts of ecotropic Friend murine leukemia helper virus gag- and env-encoded cell surface and intracellular proteins compared with leukemic cells tested 8-10 d after virus inoculation. In contrast, the spleen focus-forming virus-induced protein, gp55, was present on both leukemia cell populations. This difference appeared to be mediated by the humoral antibody response in Rfv-3r/s mice, which could recognize only ecotropic gag and env proteins, and not gp55. A new gp70 molecule cross-reactive with a recombinant Friend mink cell focus-inducing virus was found in large quantities on late leukemic cells. This protein appeared to be derived from a recombinant virus produced during the course of Friend virus infection. The appearance of this new gp70 suggests that recombinant viruses other than spleen focus-forming virus may play a role in Friend virus-induced erythroleukemia.
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PMID:New cell surface gp70 related to Friend mink cell focus-inducing virus is expressed on Friend virus-induced erythroleukemic spleen cells after elimination of ecotropic Friend virus gp70 in Rfv-3r/s mice. 697 19

Mycobacterial infection has been implicated as a possible factor in AIDS progression in populations where HIV-1 and Mycobacterium tuberculosis are coendemic. In support of this concept, we have previously shown that HIV-1-transgenic (Tg) mice infected with mycobacteria display enhanced viral gene and protein expression. In this study, we demonstrate that the induction of HIV-1 observed in this model is dependent on Toll-like receptor 2 (TLR2), a pattern recognition receptor known to be involved in mycobacteria-host interaction. Spleen cells from HIV-1-Tg mice deficient in TLR2 (Tg/TLR2(-/-)) were found to be completely defective in p24 production induced in response to live M. tuberculosis or Mycobacterium avium as well as certain mycobacterial products. Importantly, following in vivo mycobacterial infection, Tg/TLR2(-/-) mice failed to display the enhanced HIV-1 gag/env mRNA and p24 protein synthesis exhibited by wild-type Tg animals. Together, these results argue that TLR2 plays a crucial role in the activation of HIV-1 expression by mycobacterial coinfections.
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PMID:Cutting edge: in vivo induction of integrated HIV-1 expression by mycobacteria is critically dependent on Toll-like receptor 2. 1287 96

Combined antiretroviral therapy (cART) does not eradicate HIV, which persists for years and can re-establish replication if treatment is stopped. The current challenge is identifying those tissues harboring virus through cART. Here, we used HIV env-nef single genome sequencing and HIV gag droplet digital PCR (ddPCR) to survey 50 tissues from five subjects on cART with no detectable plasma viral load at death. The spleen most consistently contained multiple proviral and expressed sequences (4/5 participants). Spleen-derived HIV demonstrated two distinct phylogenetic patterns: multiple identical sequences, often from different tissues, as well as diverse viral sequences on long terminal branches. Our results suggested that ddPCR may overestimate the size of the tissue-based viral reservoir. The spleen, a lymphatic organ at the intersection of the immune and circulatory systems, may play a key role in viral persistence.
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PMID:The Spleen Is an HIV-1 Sanctuary During Combined Antiretroviral Therapy. 2908 41