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)

Human T-lymphotropic virus type I (HTLV-I) was the first retrovirus which was directly associated with adult T-cell leukemia (ATL). Infection with HTLV-I can also lead to various other diseases, e.g. HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and HTLV-I uveitis, possibly via induction of immunodeficiency or hyperreactivity against HTLV-I-infected cells. Epidemiological data have shown that patients who developed these diseases represent a small percentage of HTLV-I-infected individuals living in restricted geographical areas. The identification of HTLV-I-infected individuals using serological and DNA-diagnostic methods is important because knowledge of HTLV-I seropositivity may help to prevent the transmission between sexual partners, as well as transmission from mother to child and blood transfusion. It also assists in establishing a diagnosis of ATL, HAM/ TSP and other HTLV-I-associated diseases.
 ...
PMID:DNA diagnosis of HTLV-I. 905 68

Fas/APO-1 mediates apoptosis via Fas and Fas ligand transduction. Recently, a soluble form of Fas (sFas) was described which seems to be functionally implicated in the Fas signal system, suggesting a relationship between some disorders and sFas function. We measured sFas-levels in sera from normal controls and patients with disorders linked to human retroviral infection of human immunodeficiency virus (HIV) and human T-cell leukemia virus type-1 (HTLV-1). The sFas level of normal controls. HTLV-1 carriers seronegative for HIV, and patients with HTLV-1 associated myelopathy/tropical paraparesis (HAM/TSP), adult T-cell leukemia (ATL), and AIDS was 1.62 +/- 0.49, 1.90 +/- 0.49, 2.00 +/- 0.59, 3.32 +/- 2.05, and 3.06 +/- 0.92 ng/ml, respectively. Although the level of sFas in patient groups with HAM/TSP, ATL, and AIDS was significantly high in comparison to that of normal controls (p < 0.01), the individual values were highly variable within the groups. The sFas level was statistically correlated to the soluble interleukin-2 receptor (sIL-2R) level, as well as to cells expressing membrane Fas (mFas), indicating the same cellular origin. In some ATL cases, however, serum sFas levels and mFas expression density on leukemic T-cells were discrepant, with especially high levels of the soluble form and a lack of expression of the membrane form observed in 2 cases, sFas detection could serve as a putative marker for active diseases in patients with ATL and AIDS.
 ...
PMID:Serum levels of soluble Fas/APO-1 receptor in human retroviral infection and associated diseases. 914 6

The localization of mammalian retroviruses to specified immune organs has significant implications on the pathophysiology of retroviral associated diseases. Human T-cell Lymphotropic Virus Type I (HTLV-I) is considered a CD4+ lymphotropic virus although the virus has been shown to infect a large variety of cells in vitro. Similarly, the human immunodeficiency virus (HIV), once thought to be harbored only in CD4+ peripheral blood lymphocytes (PBL) has been shown to be present in latent form in lymph nodes of HIV infected patients. HTLV-I Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a chronic progressive neurologic disorder of the central nervous system and is believed to result from infection of HTLV-I in association with an immunopathogenic or autoimmune mechanism. Here we describe experiments which utilize the in situ hybridization/polymerase chain reaction technology to demonstrate extensive HTLV-I infection of bone marrow in HAM/TSP patients. We discuss these results in the context of HTLV-I associated neurologic disease and extend these observations to other disorders of potential retroviral etiology and autoimmune involvement.
 ...
PMID:Immunopathogenesis of HTLV-I associated neurologic disease: massive latent HTLV-I infection in bone marrow of HAM/TSP patients. 920 3

We have previously shown, using human T-cell lymphocytotrophic virus-I (HTLV-I)-infected cell lines, that soluble interleukin-6 receptor (sIL-6R) is generated through an alternative splicing mechanism. In this study, we examined human sera for the presence of alternatively spliced soluble IL-6R (AS-sIL-6R). We produced a monoclonal antibody (mAb) recognizing the unique sequence of AS-sIL-6R peptide, generated by an altered reading frame. We also made recombinant AS-sIL-6R protein in Spodoptera frugiperda-9 (Sf-9) cells carrying baculovirus, which encoded altered sIL-6R or conventional IL-6R cDNA. mAbs specifically recognized AS-sIL-6R, but not conventional IL-6R, as demonstrated by Western blot analyses, fluorescence-activated cell sorter, immunofluorescence analyses and enzyme-linked immunosorbent assay (ELISA). We adapted an ELISA system and used it for detection of altered sIL-6R in sera from 23 healthy persons, 12 patients with adult T-cell leukaemia (ATL) and 13 patients with HTLV-I-associated myelopathy (HAM). Serum levels of AS-sIL-6R were 6.4 or 6.1 times greater in ATL (28.7+/-20.4 ng/ml, P<0.0001) and in HAM patients (27.5+/-12.1 ng/ml, P<0.0001) than in healthy individuals (4.5+/-2.1 ng/ml). High levels of AS-sIL-6R were also observed in plasma from rheumatoid arthritis patients and in persons with elevated levels of alanine aminotransferase (ALT), antinuclear antibody (ANA), or alpha-fetoprotein (AFP). However, in human immunodeficiency virus-1 (HIV-1), hepatitis B virus (HBV) or hepatitis C virus (HCV)-infected individuals, AS-sIL-6R levels were not elevated. In this study, we confirmed that AS-sIL-6R is indeed present in human sera. These observations suggest that alternative splicing of IL-6R mRNA is of consequence in ATL, HAM and in some autoimmune diseases. The HTLV-I-infected T cells appeared to play an important role in AS-sIL-6R production.
 ...
PMID:High-level production of alternatively spliced soluble interleukin-6 receptor in serum of patients with adult T-cell leukaemia/HTLV-I-associated myelopathy. 982 98

The solution structure of the capsid protein (CA) from the human T-cell leukemia virus type one (HTLV-I), a retrovirus that causes T-cell leukemia and HTLV-I-associated myelopathy in humans, has been determined by NMR methods. The protein consists of independent N and C-terminal domains connected by a flexible linker. The domains are structurally similar to the N-terminal "core" and C-terminal "dimerization" domains, respectively, of the human immunodeficiency virus type one (HIV-1) and equine infectious anemia virus (EIAV) capsid proteins, although several important differences exist. In particular, hydrophobic residues near the major homology region are partially buried in HTLV-I CA, which is monomeric in solution, whereas analogous residues in HIV-1 and EIAV CA project from the C-terminal domain and promote dimerization. These differences in the structure and oligomerization state of the proteins appear to be related to, and possibly controlled by, the oxidation state of conserved cysteine residues, which are reduced in HTLV-I CA but form a disulfide bond in the HIV-1 and EIAV CA crystal structures. The results are consistent with an oxidative capsid assembly mechanism, in which CA oligomerization or maturation is triggered by disulfide bo nd formation as the budding virus enters the oxidizing environment of the bloodstream.
 ...
PMID:Solution structure of the capsid protein from the human T-cell leukemia virus type-I. 1043 34

The purpose of this review is to present some concepts on the etiology of tropical spastic paraparesis or human T-cell lymphotropic virus-I (HTLV-I)-associated myelopathy (TSP/HAM). The large number of syndromes that have been associated with HTLV-I (60 to date), the existence of TSP/HAM cases associated with other retroviruses (human immunodeficiency virus-2 [HIV-2], HTLV-II), the existence of many TSPs without HTLV-I, and the evidence of clear epidemiologic contradictions in TSP/HAM indicate that the etiopathogenesis of TSP/HAM is not yet clear. Tropical spastic paraparesis/HAM affects patients of all human ethnic groups, but usually in well localized and relatively isolated geographic regions where HTLV-I has been endemic for a long time. Environmental factors and geographic locations appear to be critical factors. Because the neuropathology of TSP/HAM suggests a toxometabolic, rather than a viral cause, it is proposed that an intoxication similar to neurolathyrism could account for some of TSP/HAM cases, mainly in tropical and subtropical countries. If this were the case, HTLV-I could be a cofactor or act as a bystander. it is possible that co-infection with another agent is necessary to produce TSP/HAM and most of the syndromes associated with HTLV-I.
 ...
PMID:On the etiology of tropical spastic paraparesis and human T-cell lymphotropic virus-I-associated myelopathy. 1046 Sep 31

HTLV-I and HTLV-II infect T lymphocytes. A high HTLV-I proviral load in peripheral blood mononuclear cells (PBMCs) has been associated with a higher risk of neurologic disease. For HTLV-II, large numbers of infected lymphocytes might contribute to accelerate the immunodeficiency and increase the risk of neuropathy in HTLV-II/HIV-1 coinfected people. We have examined the impact of antiretroviral drugs on HTLV proviral load, testing longitudinal samples collected from 1 HTLV-I infected patient suffering HTLV-I-associated myelopathy (HAM), and two HTLV-II/ HIV-1 coinfected subjects. The HAM patient showed a reduction greater than 2 log in the peripheral proviral load after being treated with zidovudine and lamivudine. In contrast, potent antiretroviral treatment in HIV-1/HTLV-II coinfected carriers produced an initial increase in the HTLV proviral load, which was followed by a reduction greater than 1 log thereafter. In conclusion, antiretroviral drugs seem to reduce HTLV proviral load, although in HIV-1 coinfected persons a transient increase in HTLV proviral load could reflect the rapid blocking of HIV-1 replication occurring in response to therapy, thus causing an increase in the number of circulating T lymphocytes carrying HTLV proviral DNA.
 ...
PMID:In vivo fluctuation of HTLV-I and HTLV-II proviral load in patients receiving antiretroviral drugs. 1093 97

Infection with human T cell leukemia virus type 1 (HTLV-1) can result in the development of HAM/TSP, a nonfatal, chronic inflammatory disease involving neuronal degeneration and demyelination of the central nervous system. Elevated levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1 observed in the cerebrospinal fluid of HAM-TSP patients suggest that cytokine dysregulation within the CNS is involved in neuropathogenesis. HTLV-1 infection and enhanced expression of TNF-alpha by microglial cells, astrocytes, and macrophages has been hypothesized to lead to the destruction of myelin and oligodendrocytes in the CNS. Although the association of HTLV-2 infection and development of neurological disease is more tenuous, HTLV-2 has also been found to be associated with peripheral neuropathies. To investigate the roles of HTLV Tax(1) and Tax(2) in the induction of cytokine disregulation in these cell types, we are currently developing gene delivery vectors based on human immunodeficiency virus type-1 (HIV-1) capable of stably coexpressing the HTLV-1 or -2 tax and eGFP reporter genes in primary human cells. Transduction frequencies of up to 50%, as assessed by eGFP expression, can be achieved in human monocyte-derived macrophages and in explanted cultures of human microglia. Preliminary data suggest that Tax(1) expression is sufficient to up-regulate the proinflammatory cytokine profile in explanted human microglial cells. Future experiments will compare and evaluate the effect of tax(1) and tax(2) gene expression on the cellular proinflammatory cytokine expression profile, as well as demonstrate the effects of transducing human fetal astrocytes and PBMC-derived macrophages.
 ...
PMID:HTLV type 1 Tax transduction in microglial cells and astrocytes by lentiviral vectors. 1108 Aug 25

Opportunistic infections frequently occur in patients with adult T-cell leukemia (ATL) and human T-cell leukemia virus type I (HTLV-I) carriers. However, the underlying mechanisms of such infections remain unknown. To clarify the mechanism of immunodeficiency in those infected with HTLV-I, this study analyzed the T-cell subsets in HTLV-I carriers and patients with HTLV-I-associated myelopathy/tropical spastic paraparesis and ATL using 3-color fluorescence with CD62L and CD45RA coexpression either with CD4(+) or CD8(+) T cells. The number of naive T lymphocytes was markedly suppressed in patients with ATL, particularly in those with acute form, compared with uninfected control individuals. The number of naive T cells was low in HTLV-I-infected individuals under 50 years old compared with uninfected individuals, whereas the number of memory T lymphocytes was greater in HTLV-I-infected individuals. Although the increase of memory T lymphocytes correlated with HTLV-I provirus loads, no relationship was found between naive T-cell counts and provirus loads. T-cell receptor rearrangement excision circles (TRECs), which are generated by DNA recombination during early T lymphopoiesis, were quantified to evaluate thymic function in HTLV-I-infected individuals. TREC levels were lower in HTLV-I-infected individuals than in uninfected individuals. In HTLV-I carriers less than 70 years old, an increase of Epstein-Barr virus DNA in peripheral blood mononuclear cells was observed in 6 of 16 (38%) examined, whereas it was detectable in only 1 of 11 uninfected controls. These results suggested that the low number of naive T lymphocytes was due to suppressed production of T lymphocytes in the thymus, which might account for immunodeficiency observed in HTLV-I-infected individuals.
 ...
PMID:Impaired production of naive T lymphocytes in human T-cell leukemia virus type I-infected individuals: its implications in the immunodeficient state. 1134 46

The correlation between virus load and specific cytotoxic T-lymphocyte (CTL) frequency during the chronic phase in human immunodeficiency virus type 1 (HIV-1) infection has been found to be negative in cross-sectional studies. We report here that, in infection with the related retrovirus human T-cell leukaemia virus type 1 (HTLV-1), the correlation is positive in asymptomatic carriers and zero in patients with the associated inflammatory disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). We demonstrate that the direction of the correlation may depend on the efficacy of the CTL response using mathematical models. We conclude that the CTL response is effective in asymptomatic carriers of HTLV-1, but ineffective in patients with HAM/TSP. Virus-mediated impairment of specific CTL production in HIV-1 infection can account for the negative correlation observed.
 ...
PMID:Cytotoxic T-cell abundance and virus load in human immunodeficiency virus type 1 and human T-cell leukaemia virus type 1. 1141 Jan 46


<< Previous 1 2 3 4 5 6 7 Next >>