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)

Perinatal infection of susceptible mice with the neurotropic retrovirus CasBrE leads to a noninflammatory spongiform degeneration of the central nervous system with a long incubation period of up to 1 year. Virus replication in infected animals can be suppressed by administration of antiviral antibodies, cytotoxic T cells, or by AZT treatment, which results in partial to complete protection from neurological disease. A highly neuropathogenic chimeric retrovirus, FrCasE, which contains the envelope gene of CasBrE, induces rapid neurodegeneration within only 16 days. Here we report that this fatal disease could be prevented if a nonneuropathogenic Friend murine leukemia virus was administered to mice prior to their infection with FrCasE. This double inoculation led to a substantial reduction of the replication level of FrCasE in spleen and CNS. Only live but not heat-inactivated nonneuropathogenic virus was able to protect from FrCasE-induced neurological disease. The extent of protection was influenced by the viral envelope gene and the kinetics of replication of the nonneuropathogenic virus. These observations in addition to the rapidity of the effect make it likely that competition for replication sites through the mechanism of viral interference is responsible for the protection. Resistance was demonstrable in vivo even when the "protecting" and "challenge" virus belonged to different in vitro interference groups. However, the protection was considerably weaker than that seen between viruses belonging to the same interference group.
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PMID:Prevention of retrovirus-induced neurological disease by infection with a nonneuropathogenic retrovirus. 783 92

FrCasE is a highly neurovirulent murine leukemia virus which causes a noninflammatory spongiform neurodegenerative disease after neonatal inoculation. The central nervous system (CNS) infection is wide-spread, involving several different cell types, whereas the lesions are localized to motor areas of the brain and spinal cord. Inoculation of FrCasE at 10 days of age (P10) results in viremia, but infection of the CNS is restricted and neurological disease is not observed (M. Czub, S. Czub, F. McAtee, and J. Portis, J. Virol. 65:2539-2544, 1991). In this study, we used this developmental resistance to restrict the extent and the distribution of FrCasE in the brain to examine whether the spongiform degeneration is a consequence of infection of cells in proximity to the lesions. Two approaches were used to infect the brain on or after P10. First, mice were inoculated with FrCasE at P10 to induce viremia and then at P17 were subjected to focal CNS injury within brain regions known to be susceptible to virus-induced spongiform degeneration. The injury resulted in local inflammation, glial activation, migration of inflammatory cells into the wound site, and high-level parenchymal infection about the wound site. However, no evidence of spongiform neurodegeneration was observed over a period of 3 months. The second approach involved the implantation of FrCasE-infected microglia into the CNS at > or = P10. This resulted in microglial engraftment and focal CNS infection unilaterally at the implantation sites and bilaterally along white matter tracts of the corpus callosum and pons and in cells of the subventricular layers of the lateral cerebral ventricles. Strikingly, focal spongiform degeneration colocalized with the sites of infection. In contrast to the wounding experiments, the implantation model was not associated with an inflammatory response or significant glial activation. Results of these studies suggest that (i) the developmental resistance of the CNS to infection lies at the blood-brain barrier and can be bypassed by direct introduction into the brain of virus-infected cells, (ii) the neuropathology induced by this virus is a consequence of local effects of the infection and does not appear to require endothelial or neuronal infection, and (iii) elements of the inflammatory response and/or glial activation may modulate the expression of neuropathology induced by neurovirulent retroviruses.
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PMID:Induction of focal spongiform neurodegeneration in developmentally resistant mice by implantation of murine retrovirus-infected microglia. 785 73

Newborn NFS/N mice are susceptible to the neurological disease induced by infection with Cas-Br-M murine leukemia virus (Cas), and do not develop a protective cytotoxic T cell (CTL)-mediated response to Cas infection. Here we demonstrate that whole UV light-inactivated Cas (UV-Cas), inoculated in newborn NFS/N mice, induced a strong, Cas-specific CTL response detectable 2 weeks postinoculation and persisting in vivo for > or = 36 weeks. The magnitude of the UV-Cas-induced splenic CTL response, mediated by CD8+ T cells, inversely correlated with the level of proviral cas env sequences detectable in the spleen of the UV-Cas-inoculated mice, as revealed by PCR amplification of tissue DNA. The transfer of UV-Cas-primed splenocytes, with Cas-specific CTL activity, protected 100% of recipient newborn mice from the development of neurological disease induced by infection with live Cas, for more than 28 weeks, and reduced the level of viral replication in the recipients.
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PMID:Ultraviolet-light-inactivated Cas-Br-M murine leukemia virus induces a protective CD8+ cytotoxic T lymphocyte response in newborn mice. 788 29

Human retroviral infections result in significant neoplastic disease. Human T cell lymphotropic virus I (HTLV-I), the first human retrovirus to be discovered, is associated with the development of acute T cell leukemia with characteristic hypercalcemia and skin lesions after many years of chronic infection of CD4+ cells. HTLV-I also produces myelopathy. A minor T cell immunodeficiency occurs in HTLV-I acute T cell leukemia with associated strongyloidiasis and Pneumocystis carinii pneumonia. Human T cell lymphotropic virus II (HTLV-II) is found to be endemic in Amerindians and intravenous drug users (IVDUs) and has been linked to some cases of hairy-cell leukemia. HTLV-II infects the CD8+ population, with significant cell-associated viremia. Clinical neurological disease is rare, with one patient with myelopathy having been described. Immunodeficiency does not seem to occur. Human immunodeficiency virus 1 (HIV-1) produces aggressive large cell and Burkitt's lymphoma in as many as 10% of HIV-1-infected patients. More than 20% of homosexual men infected with HIV-1 develop Kaposi's sarcoma (KS). The pathogenesis of KS is better understood through studying KS-like cell lines that induce angiogenic factors. In some patients HIV-1 and HTLV-I or HTLV-II infections occur concomitantly. HIV-1 accelerates the tumorigenesis of HTLV-I and produces unusual skin diseases when combined with HTLV-II. Immunodeficiency occurs in all HIV-1-infected patients.
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PMID:Human retroviruses and neoplastic disease. 790 70

Reported is a study of the human T-cell lymphotropic virus type 1 (HTLV-1) seroprevalence in Zimbabwe. HTLV-1, a retrovirus, is known to cause myelopathy and adult T-cell leukemia. Three widely separated collection sites were used. Three testing techniques, the enzyme-linked immunosorbent assay (ELISA) (Dupont), the particle agglutination test, and ELISA (Virgo) were employed in processing the sera samples. All positives were confirmed using Western blot analysis (Dupont). Of the 1082 specimens analyzed, only 4 were determined as being strongly positive for HTLV-1, having an optical density reading (OD) of 1.5-2.0 using ELISA techniques. 8 patients were determined to have leukemia, 23 were hemophiliacs, and 88 were HIV-seronegative "AIDS" patients. None of these patients were HTLV-1 positive. There were 32 neurologically diseased patients; 11 (34.4%) were found to be HIV-seropositive and 3 were HTLV-1 seropositive. 2 of the 11 HIV-positive patients also tested positive for HTLV-1. Clinical histories of the 3 HTLV-1 seropositive patients are described. Case 1 was a 53-year-old, HIV-positive man who demonstrated problems in walking and urinary incontinence. Upon examination, it was determined he had a spastic quadraparesis with loss of sphincter control. Case 2 was a 21-year-old woman who reported a 5 month history of neurological symptoms. She was HIV seropositive and showed a loss of feeling in the thorax area of her body. Sphincter muscle control was also lacking. She deteriorated rapidly and died. Case 3 was a 38-year-old woman who had deteriorating weakness in her legs until, after 3 years, she could no longer walk. She was HIV seropositive. All 3 cases had normal myelograms. This study demonstrates that the prevalence of HTLV-1 is very low in Zimbabwe. There appears to be a strong association between spinal cord disease and HTLV-1 seropositivity. Co-infections of HTLV-1 and HIV-1 were also proven. These cases generally resulted in a faster progression of the neurological disease than seen in patients solely infected with HIV-1 or HTLV-1. HTLV-1 should be considered in any patient who displays an unexplainable spinal cord disease.
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PMID:Human T cell lymphotropic virus type 1 in Zimbabwe. 803 62

Human T-cell leukemia virus (HTLV-I) induces adult T cell leukemia/lymphoma (ATL) and a chronic neurological disease named either tropical spastic paraparesis (TSP) or HTLV-I associated myelopathy (HAM). We report here the establishment and characterization of eight HTLV-I-infected lymphoid cell lines derived either from patients with TSP (5) or from asymptomatic carriers (1). Southern blot analysis of T cell beta chain gene rearrangements indicates that all cell lines are composed of clonal populations. The same type of analysis performed with HTLV-I-specific probes showed that they harbor 1 to 5 copies of full length proviruses often associated with deleted proviruses with a restriction map for BamHI, HindIII, PstI and SacI restriction enzymes resembling those of HTLV-I previously isolated from Japan and Caribbean area. One of the cell lines, 2060, derived from a TSP patient was shown to express a relative large amount of virus easily transmissible to fresh peripheral and cord blood lymphocytes. The full length proviral genome contained in this cell line was cloned and used in transient expression experiments. We showed that the cloned provirus was able to direct the synthesis of the major structural viral proteins, the protease and the tax and rex regulatory proteins. The structural viral proteins could be assembled into free particles detected in the culture medium of transfected cells. Although the infectivity of these viral particles remains to be determined, this new clone can be employed to examine the cell types in which this TSP-derived provirus directs viral protein synthesis and eventually replicates. It should also prove of value in studies on the early cellular events induced by viral products.
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PMID:Establishment of HTLV-I-infected cell lines from French, Guianese and West Indian patients and isolation of a proviral clone producing viral particles. 810 63

ts1, a mutant of Moloney murine leukemia virus, causes neurologic disorders and acute immunodeficiency associated with the destruction of thymocytes and helper T cells. In this study, we examined whether apoptosis was involved in ts1-induced killings of T cells. Neonatal mice were inoculated with ts1, and 20 to 23 days postinoculation, when cytopathic effects on T cells normally appear, thymocytes and splenic lymphocytes were isolated and examined. Our results showed that several features of apoptosis were present in ts1-infected thymocytes and splenic lymphocytes. Apoptotic fragmented DNA, condensation of the chromatin, and enhanced cell death after stimulation with mitogens which was preventable with protein synthesis inhibitors, all of which are common features of apoptotic cell death, were observed in ts1-infected cells. Several other viruses, including human immunodeficiency virus, have been shown to cause apoptotic death of T cells. Here we show for the first time that a murine retrovirus which also induces immunodeficiency can cause apoptotic T-cell death. Future studies with this murine retrovirus may provide important results to help us better understand the mechanisms of retrovirus-induced apoptosis of T cells.
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PMID:Murine retrovirus-induced depletion of T cells is mediated through activation-induced death by apoptosis. 813 49

Neonatal FVB/N mice inoculated with ts1, a temperature-sensitive mutant of Moloney murine leukemia virus TB, developed fatal immunodeficiencies and neurologic disorders. In this study, we tested the role of transfer of maternal humoral immunity in preventing ts1-induced disease syndrome in the neonatal mice. We compared the levels of protection provided through maternal antibodies both pre- and postnatally by separating infected neonatal mice into four different groups. The first group was born of and nursed by nonimmune mothers, the second was born of immune mothers but nursed by nonimmune mothers, the third was born of nonimmune mothers but nursed by immune mothers, and the fourth was born of and nursed by immune mothers. Our major findings are: (1) adult mice generate a strong antiviral antibody response; (2) maternal antibody is protective for the newborns and primarily transferred by breast milk; (3) virus titers were cleared in the periphery and the CNS of neonates nursing on immune mothers; and (4) the majority of antiviral antibody generated was specific for the gp70. These results indicate that humoral immunity can be passed efficiently from mother to baby through breast milk and can provide strong protection against neurotropic retrovirus.
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PMID:Mother-to-baby transfer of humoral immunity against retrovirus-induced neurologic disorders and immunodeficiency. 825 48

Human T-lymphotropic virus type 1 (HTLV-I) has an etiologic role in adult T-cell leukemia (ATL) and HTLV-I associated myelopathy (HAM). This paper reviews the ophthalmic literature relevant to the retrovirus. Patients with ATL may have intraocular invasion of proliferated T lymphocytes, lymphomatous lesion in the ocular adnexa, or cytomegalovirus retinitis due to immunocompromisation. Patients with the chronic neurological disease HAM may present with retinal vasculitis, isolated cotton-wool spots, probably immune-mediated uveitis, and/or retinochoroidal degenerative change. Similar retinal vascular or uveal inflammatory disease is occasionally seen in otherwise healthy HTLV-I carriers. Clinical and epidemiologic data suggest the existence of HTLV-I associated uveitis (HAU) that is assumed to be associated with the retrovirus. Further ophthalmic research is encouraged to elucidate the clinical significance of the worldwide HTLV-I infection.
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PMID:[HTLV-I and ocular disease]. 831 63

The Cas-Br-E murine leukemia virus induces a spongiform myeloencephalopathy in susceptible mice. We constructed transgenic mice harboring either the viral genome (in a replication-defective form) or only its env gene. Low levels of expression of either transgene resulted in mild neuropathology and/or signs of neurological disease in more than half of these mice. These results indicate that the disease can occur in the absence of virus replication and strongly suggest that the env gp70/p15E complex is sufficient to induce disease.
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PMID:Neurological disease induced in transgenic mice expressing the env gene of the Cas-Br-E murine retrovirus. 838 54


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