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

The human T cell leukemia virus, type 1 (HTLV-1), Rex protein mediates the nuclear export of unspliced and incompletely spliced viral mRNAs. This post-transcriptional activity is dependent in part on the binding of this protein to cis-regulatory sequences termed the Rex-response element (XRE). We have proposed previously that the decreased functionality exhibited by Rex in human lymphoblastoid Jurkat T cells may be linked to alterations in the Rex/XRE interactions. The analysis of the ribonucleoprotein complexes formed between Jurkat nuclear proteins and XRE-RNA led to the identification of a 36-kDa protein as heterogeneous nuclear ribonucleoprotein (hnRNP) A1. In vitro binding assays revealed that hnRNP A1 proteins were found to interfere with the binding of Rex to XRE, whereas nuclear extracts depleted of these proteins were unable to disrupt Rex-XRE complexes. Furthermore, A1 proteins from Jurkat cells were acting in a concentration-dependent manner, suggesting that the amount of these RNA-binding proteins is a critical parameter in controlling Rex activity. We indeed observed a lower level of hnRNP A1 in in vitro HTLV-1-transformed virus-producing T cells than that detected in Jurkat cells. Likewise, overexpression of hnRNP A1 proteins in 293T cells and in Jurkat cells led to a decrease in the expression of a reporter gene dependent on Rex/XRE interactions. Such a decrease was not observed when the expression of the same reporter gene by cells overexpressing hnRNP A1 was dependent on the interactions of human immunodeficiency virus Rev protein with the Rev-response element. These findings indicate that hnRNP A1 by competing with Rex for the formation of REX-XRE complexes is specifically involved in the modulation of the post-transcriptional activity of Rex.
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PMID:Heterogeneous nuclear ribonucleoprotein A1 interferes with the binding of the human T cell leukemia virus type 1 rex regulatory protein to its response element. 1189 30

AIDS is caused by the human T cell leukemia virus (HTLV) or lymphadenopathy associated virus (LAV) or human immunodeficiency virus (HIV). The latter name has been widely accepted. According to the WHO in 1988 there were 5 million infected persons. In Argentina, there were 300 AIDS patients and 30,000 infected people in 1989 and 60,000 in 1990. Obstacles to prevention of the spread of AIDS are: fear which causes some to conceal its existence; prolonged latency; complacency about future negative outcome; the lack of value of life among drug addicts; adolescent behavior of defiance and confrontation; militant denial by many of the possibility of contracting AIDS; and a criminally low level of measures to combat AIDS in the Third World. Primary prevention includes avoidance of contact with body fluids of an infected person submitting to a serological test if infection is suspected massive educational campaigns, study of subcultures such as drug addicts and adolescents, use of disposable needles and sterilization of all medical instruments use of condoms, and analysis of the blood of donated organs and blood for transfusion. Secondary prevention means making sure that seropositive patients undergo periodic medical checkups and receive medical attention when suspicious symptoms are detected and follow various steps to strengthen their immune systems. Tertiary prevention comprises psychological and psychopharmacological treatment of emotional distress to facilitate a less painful progress of the disease and to avert possible complications and relapses.
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PMID:[AIDS: behavioral contributions to its prevention]. 1228 43

The human T-cell leukemia virus type 1 (HTLV-1) and human immunodeficiency virus type 1 (HIV-1) retroviruses are two evolutionary distinct human pathogens. HTLV-1 is the etiologic agent of two diverse diseases: adult T-cell leukemia/lymphoma, as well as the neurologic disorder tropical spastic paraparesis/HTLV-1-associated myelopathy. HTLV-1 is the only retrovirus known to be the etiologic agent of human cancer. HTLV-2, the other known oncovirus, is not apparently associated with human cancer. While HTLV-1 transforms T-cells in vitro, HIV kills CD4+ T-cells and is the etiological agent of human acquired immunodeficiency syndrome, characterized by a progressive loss of CD4+ cells, weakening of the immune system, and susceptibility to opportunistic infections and cancer. HTLV-1 and HIV-1 both cause lifelong infections, which suggests that they have evolved mechanism(s) to evade detection by the host's immune response; particularly to evade cytotoxic T-lymphocytes, which play a major role in cellular immunity against viruses and will be the focus of this review.
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PMID:Retroviral proteins that target the major histocompatibility complex class I. 1229 31

To assess the prevalence of human T cell leukemia virus type I (HTLV-I) and 2 (HTLV-II) infection and the associated risk factors among immigrants living in Northern Italy, we surveyed 3017 open-population subjects from three geographical areas and 371 prisoners. In the open population, the overall prevalence was 0.3% for HTLV-I and 0.1% for HTLV-II, while among prisoners, HTLV-I and HTLV-II infection were detected in 1.4 and 0.8% of subjects, respectively. HTLV-I prevalence was higher in subjects with multiple sexual partners or sexually transmitted diseases. This association was significant in the open-population group and close to significance in prisoners. Multivariate analysis showed that human immunodeficiency virus (HIV) seropositivity remained significantly associated with HTLV-I infection in both targeted populations (OR: 11.2 in the open population; OR: 9.9 among prisoners), whereas sexual exposure was associated with HTLV-I seropositivity only for prisoners (OR: 14.3). No independent variable was related to HTLV-II infection.
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PMID:Seroprevalence of HTLV-I and HTLV-II infection among immigrants in northern Italy. 1290 26

Infection with human T-cell lymphotrophic virus-I (HTLV-I) is now a global epidemic, affecting 10 to 20 million people. This virus has been linked to life-threatening, incurable diseases, adult T-cell leukemia/lymphoma (ATLL), and HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP), as well as several chronic illnesses, such as uveitis and dermatitis. The cumulative lifetime risk of developing these incurable diseases is approximately 5% in asymptomatic patients. For operating room personnel performing surgery among patients from high-risk groups, HTLV-I and its associated diseases are presenting an increasing challenge. This report describes its transmission, seroprevalence, treatment, and public health initiatives that must be instituted to prevent the spread of this retrovirus. Coinfection with HTLV-I and human immunodeficiency virus (HIV) has been shown to accelerate the progression of acquired immune deficiency syndrome (AIDS).
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PMID:Global epidemic of human T-cell lymphotrophic virus type-I (HTLV-I): an update. 1451 Feb 86

A computational model was recently designed to simulate cellular changes in the T cell immune system. The model was validated by simulating cell changes in viral infections which target the same CD4+ T cell, yet cause either hyperplastic, aplastic or neoplastic responses. Respective case material for comparison was available from human infections with human herpesvirus-6 (HHV-6), human immunodeficiency virus (HIV-1) or human T cell leukemia virus (HTLV-1). Starting with cell values for a healthy human individual, factorial changes that influence the individual course of the various infections were determined by an algorithm search procedure. Such factorial differences determining a clinical course with aplasia, hyperplasia or neoplasia are outlined and further discussed in this paper.
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PMID:Computational simulation of chronic persistent virus infection: factors determining differences in clinical outcome of HHV-6, HIV-1 and HTLV-1 infections including aplastic, hyperplastic and neoplastic responses. 1501 96

Human T cell lymphotropic virus type 1 (HTLV-I) is causally linked to adult T cell leukemia/lymphoma (ATL) and a chronic progressive neurological disease, HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A nonhuman primate model that reproduces disease symptoms seen in HTLV-I-infected humans might facilitate identification of initial immune responses to the virus and an understanding of pathogenic mechanisms in HTLV-I-related disease. Previously, we showed that infection of pig-tailed macaques with HTLV-I(ACH) is associated with multiple signs of disease characteristic of both HAM/TSP and ATL. We report here that within the first few weeks after HTLV-I(ACH) infection of pig-tailed macaques, serum concentrations of interferon (IFN)-alpha increased and interleukin-12 decreased transiently, levels of nitric oxide were elevated, and activation of CD4(+) and CD8(+) lymphocytes and CD16(+) natural killer cells in peripheral blood were observed. HTLV-I(ACH) infection elicited virus-specific antibodies in all four animals within 4 to 6 weeks; however, Tax-specific lymphoproliferative responses were not detected until 25-29 weeks after infection in all four macaques. IFN-gamma production by peripheral blood cells stimulated with a Tax or Gag peptide was detected to varying degrees in all four animals by ELISPOT assay. Peripheral blood lymphocytes from one animal that developed only a marginal antigen-specific cellular response were unresponsive to mitogen stimulation during the last few weeks preceding its death from a rapidly progressive disease syndrome associated with HTLV-I(ACH) infection of pig-tailed macaques. The results show that during the first few months after HTLV-I(ACH) infection, activation of both innate and adaptive immunity, limited virus-specific cellular responses, sustained immune system activation, and, in some cases, immunodeficiency were evident. Thus, this animal model might be valuable for understanding early stages of infection and causes of immune system dysregulation in HTLV-I-infected humans.
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PMID:Immune responses to HTLV-I(ACH) during acute infection of pig-tailed macaques. 1515 63

The human T cell leukemia virus and the human immunodeficiency virus share a highly conserved, predominantly helical two-domain mature capsid (CA) protein structure with an N-terminal beta-hairpin. Despite overall structural similarity, differences exist in the backbone dynamic properties of the CA N-terminal domain. Since studies with other retroviruses suggest that the beta-hairpin is critical for formation of a CA-CA interface, we investigated the functional role of the human T cell leukemia virus beta-hairpin by disrupting the salt bridge between Pro(1) and Asp(54) that stabilizes the beta-hairpin. NMR (15)N relaxation data were used to characterize the backbone dynamics of the D54A mutant in the context of the N-terminal domains, compared with the wild-type counterpart. Moreover, the effect of the mutation on proteolytic processing and release of virus-like particles (VLPs) from human cells in culture was determined. Conformational and dynamic changes resulting from the mutation were detected by NMR spectroscopy. The mutation also altered the conformation of mature CA in cells and VLPs, as reflected by differential antibody recognition of the wild-type and mutated CA proteins. In contrast, the mutation did not detectably affect antibody recognition of the CA protein precursor or release of VLPs assembled by the precursor, consistent with the fact that the hairpin cannot form in the precursor molecule. The particle morphology and size were not detectably affected. The results indicate that the beta-hairpin contributes to the overall structure of the mature CA protein and suggest that differences in the backbone dynamics of the beta-hairpin contribute to mature CA structure, possibly introducing flexibility into interface formation during proteolytic maturation.
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PMID:Structural and dynamics studies of the D54A mutant of human T cell leukemia virus-1 capsid protein. 1556 85

Adult T-cell leukemia (ATL) was first reported as a distinct clinical entity in 1977 in Japan. The predominant physical findings are skin lesions, lymphadenopathy and hepatosplenomegaly. The ATL cells are of mature T-helper phenotype and have a characteristic appearance with indented nuclei. There is striking frequent hypercalcemia with increased numbers of osteoclasts. Central to the identification of the disease is a striking geographic clustering in southwestern Japan and the isolation of human T-cell lymphotropic virus type-1 (HTLV-1) from the cell lines of patients. Worldwide epidemiological studies have been made through international collaborations. Several diseases were found to be related to HTLV-1 infection. Moreover, it was noted that an immunodeficiency state may be induced by HTLV-1 infection. In Japan, HTLV-1 carriers have been estimated to be 1.2 million, and more than 700 cases of ATL have been diagnosed each year.
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PMID:Discovery of adult T-cell leukemia. 1574 25

Adult T-cell leukemia (ATL) develops via multiple oncogenic steps in human T-cell leukemia virus type I (HTLV-I) carriers. To better understand pathogenesis of ATL, we developed a novel xenogeneic engraftment model in which primary ATL cells are intravenously transplanted into neonatal nonobese diabetic (NOD)/severe-combined immunodeficiency (SCID)/beta2-microglobulin(null) (NOD/SCID/beta2m(null)) mice. Acute-type ATL cells engrafted in the peripheral blood and in the lymph nodes of recipients at a high efficiency. Engrafted ATL cells were dually positive for human CD4 and CD25, and displayed patterns of HTLV-I integration identical to those of donors by Southern blot analysis. These cells infiltrated into recipients' liver, and formed nodular lesions, recapitulating the clinical feature of each patient. In contrast, in smoldering-type ATL cases, multiple clones of ATL cells engrafted efficiently in NOD/SCID/beta2m(null) mice. When smoldering-type ATL cells were retransplanted into secondary NOD/SCID/beta2m(null) recipients, single HTLV-I-infected clones became predominant, suggesting that clones with dominant proliferative activity can be competitively selected in this xenogeneic system. Taken together, the NOD/SCID/beta2m(null) newborn system is useful to understand kinetics, metastasis, and disease progression of ATL in vivo.
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PMID:Efficient engraftment of primary adult T-cell leukemia cells in newborn NOD/SCID/beta2-microglobulin(null) mice. 1595 32


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