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)

Recently it has become urgent to establish a risk control system against emerging and re-emerging infectious diseases. Many of the emerging and re-emerging infectious diseases such as AIDS and viral hepatitis, are induced by viral infection via blood. The main causative agents of blood-born viral infection are hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), human T cell leukemia virus type1 (HTLV1), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human parvovirus B19. They play the main role in viral hospital infections. The risk of them being transmitted by the transfusion of screened blood is very low, but it is always possible that infection may occur in a window period even after extensive blood screening tests. EBV has been recognized as a less serious infectious agent than CMV. Nowadays, biotechnology has revealed the broad spectrum of EBV related diseases as chronic active EBV infection, compromised lymphoma, gastric carcinoma and other lymphoproliferative disorders. There would be some immunocompromised cases needed monitoring after transfusion/transplantation as same as CMV infection. Double infection or co-infection of EBV and CMV are shown to be occasional. The most important tasks for risk control of hospital acquired infectious diseases are to prevent second drug related AIDS and prion infection due to the transplantation of dura mata derived from patients with Creutzfeldt-Jakob disease, and to prevent of needle stick infections. Therefore it is necessary to establish a network communication between clinical laboratories, institutes and public health organizations for more rapid and adequate care with rapid diagnosis by molecular analysis.
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PMID:[The blood-born viral infections]. 952 33

Investigation of human antibody responses to viral pathogens at the molecular level is revealing novel aspects of the interplay of viruses with the humoral immune system. In viral infection, at least two types of human antibody responses exist: a response to mature envelope on virions that is neutralizing and a response to immature forms of envelope (viral debris) that is not. Many pathogens have, to varying degrees, evolved envelopes to minimize antibody responses against epitopes exposed on the virion. In this article, we review recent studies on human immunodeficiency virus type 1, Ebola virus, and respiratory syncytial virus. Prion diseases are diseases of protein conformation. We have generated a large panel of antibodies recognizing the cellular prion protein (PrP(c)), some of which also react with the abnormally folded infectious prion protein (PrP(Sc)). These antibodies are being used to gain insight into both the molecular events leading to the formation of infectious PrP and the physiologic role played by PrP in normal and prion-infected cells.
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PMID:Antibodies in human infectious disease. 1085 27

Prion replication in spleen and neuroinvasion after i.p. inoculation of mice is impaired in forms of immunodeficiency where mature B lymphocytes are lacking. In spleens of wild-type mice, infectivity is associated with B and T lymphocytes and stroma but not with circulating lymphocytes. We generated transgenic prion protein knockout mice overexpressing prion protein in B lymphocytes and found that they failed to accumulate prions in spleen after i.p. inoculation. We conclude that splenic B lymphocytes are not prion-replication competent and that they acquire prions from other cells, most likely follicular dendritic cells with which they closely associate and whose maturation depends on them.
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PMID:B lymphocyte-restricted expression of prion protein does not enable prion replication in prion protein knockout mice. 1127 28

Interaction between nucleic acid and recombinant murine prion protein, MoPrPC resulted in a time-dependent change in the nucleic acid morphology revealed by electron microscopy. After the addition of the protein to DNA, association of small number of nucleic acid molecules (nucleo-protein complex) was followed by aggregation of large number of them still retaining their initial linear morphology. With increase in the incubation time, ordered aggregation resulted in small condensed spherical globules. Subsequently, the formation of large condensed particles took place either by fusion of the already formed small globules or by accumulation of more nucleic acid molecules on them. The condensed nucleic acid structures observed here were different from other known morphologically altered nucleic acid structures induced by different cellular proteins. The condensed nucleic acid structures dissociated spontaneously. The formation of the prion protein-induced condensed nucleic acid structures resembled the human immunodeficiency virus 1 nucleocapsid protein NCp7-induced condensed ordered aggregates of nucleic acids. In the latter system, both the processes of condensation and dissociation of the nucleoprotein complex are believed to be responsible for the functional properties of the HIV-1 virus. Demonstration of functional activity of the prion protein-nucleic acid complex would be relevant for a role of nucleic acid in prion diseases.
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PMID:Murine recombinant prion protein induces ordered aggregation of linear nucleic acids to condensed globular structures. 1131 41

The past decade has seen major changes in the field of infectious diseases. In particular, many new infections of the nervous system have been recognised, including the lethal infections of Enterovirus 71, and the Nipah and West Nile viruses. Increased interest in prion diseases has occurred, following the recognition of animal-to-human transmission in Europe. Familiar bacteria such as the pneumococcus continue to cause problems due to increasing resistance to multiple antibiotics. Furthermore, human immunodeficiency virus-infected and other immunocompromised patients are under the constant threat of opportunistic infections, many of which are targeted towards the brain and spinal cord. This paper reviews the changing world of nervous system infections, highlighting some of the most significant recent developments.
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PMID:Infections of the nervous system: an update on recent developments. 1140 78

Leukocytes accumulate at sites of inflammation and immunological reaction in response to locally existing chemotactic mediators. N-formyl peptides, such as fMet-Leu-Phe (fMLF), are some of the first identified and most potent chemoattractants for phagocytic leukocytes. In addition to the bacterial peptide fMLF and the putative endogenously produced formylated peptides, a number of novel peptide agonists have recently been identified that selectively activate the high-affinity fMLF receptor FPR and/or its low-affinity variant FPRL1, both of which belong to the seven-transmembrane (STM), G protein-coupled receptor (GPCR) superfamily. These agonists include peptide domains derived from the envelope proteins of human immunodeficiency virus type 1 (HIV-1) and at least three amyloidogenic polypeptides, the human acute phase protein serum amyloid A, the 42 amino acid form of beta amyloid peptide and a 21 amino acid fragment of human prion. Furthermore, a cleavage fragment of neutrophil granule-derived bactericidal cathelicidin, LL-37, is also a chemotactic agonist for FPRL1. Activation of formyl peptide receptors results in increased cell migration, phagocytosis, release of proinflammatory mediators, and the signaling cascade culminates in heterologous desensitization of other STM receptors including chemokine receptors CCR5 and CXCR4, two coreceptors for HIV-1. Thus, by interacting with a variety of exogenous and host-derived agonists, formyl peptide receptors may play important roles in proinflammatory and immunological diseases and constitute a novel group of pharmacological targets.
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PMID:Receptors for chemotactic formyl peptides as pharmacological targets. 1178 60

The V3 loop of the human immunodeficiency virus (HIV)-1 surface envelope glycoprotein gp120 is a sphingolipid-binding domain mediating the attachment of HIV-1 to plasma membrane microdomains (rafts). Sphingolipid-induced conformational changes in gp120 are required for HIV-1 fusion. Galactosylceramide and sphingomyelin have been detected in highly purified preparations of prion rods, suggesting that the prion protein (PrP) may interact with selected sphingolipids. Moreover, a major conformational transition of the Alzheimer beta-amyloid peptide has been observed upon interaction with sphingolipid-containing membranes. Structure similarity searches with the combinatorial extension method revealed the presence of a V3-like domain in the human prion protein PrP and in the Alzheimer beta-amyloid peptide. In each case, synthetic peptides derived from the predicted V3-like domain were found to interact with monomolecular films of galactosylceramide and sphingomyelin at the air-water interface. The V3-like domain of PrP is a disulfide-linked loop (Cys(179)-Cys(214)) that includes the E200K mutation site associated with familial Creutzfeldt-Jakob disease. This mutation abrogated sphingomyelin recognition. The identification of a common sphingolipid-binding motif in gp120, PrP, and beta-amyloid peptide underscores the role of lipid rafts in the pathogenesis of HIV-1, Alzheimer, and prion diseases and may provide new therapeutic strategies.
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PMID:Identification of a common sphingolipid-binding domain in Alzheimer, prion, and HIV-1 proteins. 1179 5

All lentiviruses and oncoretroviruses examined so far encode a major nucleic-acid binding protein (nucleocapsid or NC* protein), approximately 2500 molecules of which coat the dimeric RNA genome. Studies on HIV-1 and MoMuLV using in vitro model systems and in vivo have shown that NC protein is required to chaperone viral RNA dimerization and packaging during virus assembly, and proviral DNA synthesis by reverse transcriptase (RT) during infection. The human cellular prion protein (PrP), thought to be the major component of the agent causing transmissible spongiform encephalopathies (TSE), was recently found to possess a strong affinity for nucleic acids and to exhibit chaperone properties very similar to HIV-1 NC protein in the HIV-1 context in vitro. Tight binding of PrP to nucleic acids is proposed to participate directly in the prion disease process. To extend our understanding of lentiviruses and of the unexpected nucleic acid chaperone properties of the human prion protein, we set up an in vitro system to investigate replication of the feline immunodeficiency virus (FIV), which is functionally and phylogenetically distant from HIV-1. The results show that in the FIV model system, NC protein chaperones viral RNA dimerization, primer tRNA(Lys,3) annealing to the genomic primer-binding site (PBS) and minus strand DNA synthesis by the homologous FIV RT. FIV NC protein is able to trigger specific viral DNA synthesis by inhibiting self-priming of reverse transcription. The human prion protein was found to mimic the properties of FIV NC with respect to primer tRNA annealing to the viral RNA and chaperoning minus strand DNA synthesis.
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PMID:Functional interactions of nucleocapsid protein of feline immunodeficiency virus and cellular prion protein with the viral RNA. 1205 75

Although Alzheimer's disease (AD) may not involve a transmissible agent, it does involve a pathogenic process similar to that of transmissible prion disorders (both involve a protein that adopts an abnormal pathogenic conformation in which it self-aggregates, forming amyloid deposits in and surrounding neurons) and viral dementias such as human immunodeficiency virus (HIV) encephalitis. The clinical presentation of patients with AD is dominated by cognitive deficits and emotional disturbances that result from dysfunction and degeneration of neurons in the limbic system and cerebral cortex. The pathogenic process in the brain involves deposition of insoluble aggregates of amyloid beta-peptide, oxidative stress and calcium dysregulation in neurons, and activation of inflammatory cytokine cascades involving microglia. However, AD patients also exhibit alterations in immune function. Studies of lymphocytes and lymphoblast cell lines from AD patients and age-matched normal control patients have documented alterations in cytokine and calcium signaling and increased levels of oxidative stress in immune cells from the AD patients. Studies of the pathogenic actions of mutations in presenilins and amyloid precursor protein that cause early-onset familial AD have established central roles for perturbed cellular calcium homeostasis and oxidative stress in the neurodegenerative process. Presenilin and amyloid precursor protein (APP) mutations also increase oxidative stress and perturb calcium signaling in lymphocytes in ways that alter their production of cytokines that are critical for proper immune responses. Immune dysfunction occurs prior to clinical symptoms in mouse models of AD, and brain cytokine responses to immune challenge are altered in presenilin mutant mice, suggesting a causal role for altered immune function in the disease process. Interestingly, immunization of AD mice with amyloid beta-peptide can stimulate the immune system to remove amyloid from the brain and can ameliorate memory deficits, suggesting that it may be possible to prevent AD by bolstering immune function.
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PMID:Oxidative stress, perturbed calcium homeostasis, and immune dysfunction in Alzheimer's disease. 1247 48

chlamdAs with other organ systems, the vulnerability of the nervous system to infectious agents increases with aging. Several different infectious agents can cause neurodegenerative conditions, with prominent examples being human immunodeficiency virus (HIV-1) dementia and prion disorders. Such infections of the central nervous system (CNS) typically have a relatively long incubation period and a chronic progressive course, and are therefore increasing in frequency as more people live longer. Infectious agents may enter the central nervous system in infected migratory macrophages, by transcytosis across blood-brain barrier cells or by intraneuronal transfer from peripheral nerves. Synapses and lipid rafts are important sites at which infectious agents may enter neurons and/or exert their cytotoxic effects. Recent findings suggest the possibility that infectious agents may increase the risk of common age-related neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and stroke. While scenarios can be envisioned whereby viruses such as Chlamydia pneumoniae, herpes simplex and influenza promote damage to neurons during aging, there is no conclusive evidence for a major role of these pathogens in neurodegenerative disorders. In the case of stroke, blood vessels may be adversely affected by bacteria or viruses resulting in atherosclerosis.
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PMID:Infectious agents and age-related neurodegenerative disorders. 1516 5


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