Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ts1 mutant of Moloney murine leukemia virus TB (MoMuLV-TB) causes a degenerative neurologic and immunologic disease in mice characterized by development of spongiform encephalomyelopathy that results in hind-limb paralysis, marked thymic atrophy associated with immunodeficiency, and generalized body wasting. T cells, particularly CD4+ helper T cells, play a key role in the pathogenesis of the disease induced by ts1. Therefore, ts1 is unique among the described murine retroviruses in its ability to afflict both the central nervous system (CNS) and the T-cell compartment of the immune system in the same host. This particular ability to cause degenerative diseases involving both the CNS and immune system is shared by the lentiviruses responsible for development of the acquired immunodeficiency syndromes of humans and macaques. Our goal has been to elucidate the specific cellular and molecular mechanisms that underlie this neuro- and immunopathogenicity of ts1. We have previously reported that the primary neuropathogenic determinant of ts1 maps to a single amino acid substitution, Val-25-Ile, in the precursor envelope protein gPr80env. Further, at the restrictive temperature, the Val-25-Ile substitution did not prevent oligomerization of the gPr80env proteins; however, the structure of the oligomer was incompetent for transport from the ER to the Golgi. These findings suggest that the cytopathic effect of ts1 in neural cells might be due to accumulation of the gPr80env oligomers in the ER. Since glial cells are targets of ts1 infection in vivo, primary astrocytic cultures were established and the cytopathic effect of ts1 and MoMuLV-TB on these cells assessed. Both viruses replicate well in astrocytes and their replication is cytopathic, albeit to different degrees. The ts1 mutant appears to produce greater cell killing than the wild-type virus. Furthermore, it was found that the rate of processing of gPr80env of ts1 in astrocytes is slower than that of MoMuLV-TB. Therefore, the inefficient transport and processing of gPr80env of ts1 appears to correlate with its cytopathic effect in these cells. Electron microscopic studies of the ts1-infected astrocytes revealed large numbers of aberrant particles in the ER. The in vitro cytopathic effect of ts1 on astrocytes may reflect what happens in vivo. An indirect mechanism of neuronal-cell killing by ts1 is proposed.
 ...
PMID:Murine leukemia virus induced central nervous system diseases. 160 15

A slow influenzal congenital infection of man (in a child aged 2.5 years) is described for the first time. The infection manifests itself by encephalomyelopathy (retarded psychomotor development, sluggish spinal pareses of the limbs) and resembles Werdnig-Hoffmann amyotrophy. Besides, one can ses neuroendocrine disorders (hypophyseal nanism, hypogonadism ) and the signs of immunodeficiency. The long-term persistence of influenza A virus, its defective form was detected in the blood and CSF by means of molecular hybridization. In addition, the summarized data on the clinical studies of congenital influenzal injuries to the CNS in children, carried out by the author are provided. The theoretical evidence for the work was experimental slow influenzal infection in mice obtained for the first time at the N.F.Gamaleia Institute of Epidemiology and Microbiology (Moscow).
 ...
PMID:[Congenital encephalomyelopathy as a possible slow infection in humans]. 164 19

The ts1 mutant of Moloney murine leukemia virus TB causes degenerative neurologic and immunologic disease in mice, characterized by development of spongiform encephalomyelopathy resulting in hindlimb paralysis, marked thymic atrophy associated with immunodeficiency, and generalized body wasting. To investigate the pathogenesis of the thymic atrophy caused by ts1, we constructed a chimeric virus, ts1-Cas(NS), in which a major portion of the U3 region of the long terminal repeat of ts1, a T-lymphotropic and neurovirulent murine leukemia virus, was replaced by the corresponding U3 region of Cas-Br-E, a B-lymphotropic and neurovirulent murine leukemia virus. In FVB/N mice, ts1-Cas(NS) induced paralytic and wasting disease with incidence, severity, and latency similar to that induced by ts1, but it failed to cause thymic atrophy as severe as that observed in ts1-infected mice. Furthermore, thymocytes cultured from ts1-Cas(NS)-infected mice died at a much slower rate than those of ts1-infected mice. The U3 substitution in ts1-Cas(NS) specifically diminished the ability of the virus to replicate in the thymus, whereas viral replication in the spinal cord was not significantly affected; thus, neurovirulence was not changed. The correlation of reduced thymic atrophy with decreased thymic viral titers and the decreased ability of ts1-Cas(NS) to cause thymocyte death in mice suggest strongly that the marked thymic atrophy in ts1-infected mice is not an indirect effect occurring secondary to neurodegenerative and wasting disease but is a direct cytopathic effect of high-level viral replication in the thymus.
 ...
PMID:Alteration from T- to B-cell tropism reduces thymic atrophy and cytocidal effects in thymocytes but not neurovirulence induced by ts1, a mutant of Moloney murine leukemia virus TB. 192 61

Human T-lymphotropic virus type I (HTLV-I) and type II (HTLV-II) are closely related retroviruses with similar biological properties and common modes of transmission. HTLV-I infection is endemic in well-defined geographic regions, and it is estimated that some 20 million individuals are infected worldwide. Although most infected individuals are asymptomatic carriers, some 2 to 5% will develop a chronic encephalomyelopathy, HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In contrast with HTLV-I, the role of HTLV-II in the development of neurological disorders is much less clear. HTLV-II is endemic in many native Amerindian groups and epidemic in injecting drug users (IDUs) worldwide. To evaluate the role of HTLV-II in neurological disease, we have critically reviewed all reported cases of HTLV-II-associated disorders. This has confirmed that although rare infection is associated with a disorder clinically similar or identical to HAM/TSP. However, most reports that have attributed infection to a range of other neurological disorders are difficult to evaluate in that in many cases either the association appears to be fortuitous or the presentations were confounded by a background of concomitant human immunodeficiency virus-1 infection and/or active IDU. In view of the many HTLV-II-infected individuals in urban areas of North America and Europe, neurologists should be aware of the potential clinical consequences of this infection.
 ...
PMID:Human T-lymphotropic virus type II and neurological disease. 1523 97

We report a case of human immunodeficiency virus (HIV)-associated vacuolar encephalomyelopathy with progressive central nervous system dysfunction and corresponding vacuolar degeneration of the spinal cord, cranial nerves, and brain, the anatomic extent of which has not previously been described.
 ...
PMID:HIV-Associated Vacuolar Encephalomyelopathy. 3141 92