Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the role of B cells in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) using B cell-deficient mice muMT) and mice bearing the X-linked immunodeficiency (xid). The mice were immunized with MOG(1-125 )in complete Freund's adjuvant but without use of pertussis toxin. B cell-deficient muMT mice on different genetic backgrounds (C57BL/10 and DBA/1 strains) developed EAE, although with a reduced clinical severity. Histological analyses revealed decreased demyelination in the central nervous system while the influx of inflammatory cells was similar or only slightly reduced as compared to B cell-sufficient control mice. Xid mice on the DBA/1 background also developed disease with a reduced disease severity. The anti-MOG antibody response in the xid mice was decreased, while the T cell response to MOG was unaffected. We thus demonstrate that B cells are not critical for the development of MOG-induced EAE but contribute to the severity. The contribution of B cells to pathogenesis appears to be mainly through demyelination rather than through inflammation.
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PMID:A comparative analysis of B cell-mediated myelin oligodendrocyte glycoprotein-experimental autoimmune encephalomyelitis pathogenesis in B cell-deficient mice reveals an effect on demyelination. 1211 14

The alpha chemokine receptor CXCR4 is used as the major coreceptor for the cell entry of T-cell-tropic human immunodeficiency virus-1 (HIV-1) isolates. Activation of this coreceptor by its natural ligand SDF1alpha is associated with an intracellular Ca(2+) increase. Because the HIV-1 glycoprotein 120 (gp120) is shedded from the surface of HIV-1-infected cells and is regarded as an injurious molecule in the pathogenesis of HIV-1-associated encephalopathy (HIVE), we investigated the effects of gp120 on the intracellular Ca(2+) regulation of astrocytes and neurons. After 5 days in vitro (DIV), SDF1alpha (50 nM) elicited a pertussis toxin-sensitive intracellular Ca(2+) increase due to Ca(2+) release from internal stores that was reduced by a blocking monoclonal antibody against the CXCR4 receptor in astrocytes and neurons. Parallel with the development of the SDF1alpha response, cells became sensitive to direct application of gp120 (1.25 microg/ml), which, similarly to SDF1alpha, elicited a transient intracellular Ca(2+) increase. However, short-term incubation with gp120 for 60 to 120 min induced a reduction of glutamate- or ATP-evoked intracellular Ca(2+) responses only in astrocytes and not in neurons, although functional CXCR4 receptors were expressed in both cell types. Therefore, our data strongly suggest that the CXCR4 receptor-mediated intracellular signaling pathway of gp120 differs in astrocytes and neurons.
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PMID:Functional CXCR4 receptor development parallels sensitivity to HIV-1 gp120 in cultured rat astroglial cells but not in cultured rat cortical neurons. 1240 67

Human immunodeficiency virus (HIV) gp120 induces multiple cellular signaling pathways, including the phosphatidylinositol 3-kinase (PI3-kinase) pathway. The role of the PI3-kinase pathway in HIV-1 replication is not understood. Here we examined whether HIV-1 gp120 upregulates the PI3-kinase pathway and whether PI3-kinase activity plays a role in virus replication in primary human CD4(+) T cells and macrophages. Soluble and virion-associated HIV-1 gp120 induced calcium mobilization and phosphorylation of the PI3-kinase downstream effectors PKB/Akt and p70 S6 kinase. gp120-induced PI3-kinase activity and calcium mobilization were inhibited by pertussis toxin and blocking antibodies directed against CCR5 and CXCR4, suggesting that the signaling is mediated through the chemokine receptor. The PI3-kinase inhibitor LY294002 inhibited infection of CD4(+) T cells and macrophages with X4 and R5 HIV-1-pseudotyped viruses at concentrations that did not induce cell toxicity or downregulate HIV-1 coreceptor expression. When gp120-induced signaling was bypassed with the vesicular stomatitis virus G envelope protein, infection was still sensitive to PI3-kinase inhibition, suggesting that basal PI3-kinase activity is required for infection. LY294002 inhibited HIV-1 infection when added after viral entry and did not affect formation of the HIV-1 reverse transcriptase products R/U5 and long terminal repeat/Gag in the presence of the inhibitor. However, when the inhibitor was added after viral integration had occurred, no inhibition of HIV infection was observed. Our studies show that inhibition of the PI3-kinase signaling pathway suppresses virus infection post-viral entry and post-reverse transcription but prior to HIV gene expression. This type of host-virus interaction has implications for anti-HIV therapeutics that target cellular signaling machinery.
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PMID:Phosphatidylinositol 3-kinase regulates human immunodeficiency virus type 1 replication following viral entry in primary CD4+ T lymphocytes and macrophages. 1255 92

Bordetella pertussis was diagnosed in a human immunodeficiency virus-infected patient by a newly developed method in which bacterial DNA is amplified directly from sputum Gram-stained slides. The validation of the method is described along with an additional new PCR-based assay that can distinguish between B. pertussis and Bordetella holmesii.
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PMID:Identification of Bordetella pertussis in a critically ill human immunodeficiency virus-infected patient by direct genotypical analysis of Gram-stained material and discrimination from B. holmesii by using a unique recA gene restriction enzyme site. 1476 70

Human immunodeficiency virus (HIV) dementia (HIVD) is associated with an increase in the number of activated monocytes within the central nervous system (CNS), a pathological feature that may be more remarkable in the setting of superimposed substance abuse. Monocytes may transport HIV to the brain, and, moreover, activated and/or infected monocytes have been shown to release a number of potent neurotoxins. Although the mechanisms responsible for the increase in the CNS ingress of monocytes are multiple, blood-brain barrier (BBB)-degrading matrix metalloproteinases (MMPs) are likely to play an important role. The current study investigates the effects of the HIV-1-encoded protein Tat, and the drug of abuse methamphetamine, on MMP release from brain derived cells. The release of urokinase plasminogen activator (uPA), an activator of MMPs, was also investigated. Mixed human neuron/astrocyte cultures were stimulated with Tat or methamphetamine, and supernatants were analyzed by enzyme-linked immunosorbent assay (ELISA) and/or gelatin substrate zymography. Results showed that Tat and methamphetamine increased the release of MMP-1 from these cultures. Tat also increased supernatant levels of active MMP-2. In addition, both Tat and methamphetamine stimulated the release of the MMP activator uPA, and in a manner that was sensitive to inhibition with pertussis toxin. Together, these results suggest that in HIVD, Tat and methamphetamine may contribute to CNS inflammation by stimulating increased release and/or activation of matrix-degrading proteinases through mechanisms that include Gi/Go-coupled signaling. These results also suggest a potential mechanism for acceleration of HIVD with methamphetamine use.
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PMID:Human immunodeficiency virus type 1 Tat and methamphetamine affect the release and activation of matrix-degrading proteinases. 1498 25

Cell-mediated immunity depends in part on appropriate migration and localization of cytotoxic T lymphocytes (CTL), a process regulated by chemokines and adhesion molecules. Many viruses, including human immunodeficiency virus type 1 (HIV-1), encode chemotactically active proteins, suggesting that dysregulation of immune cell trafficking may be a strategy for immune evasion. HIV-1 gp120, a retroviral envelope protein, has been shown to act as a T-cell chemoattractant via binding to the chemokine receptor and HIV-1 coreceptor CXCR4. We have previously shown that T cells move away from the chemokine stromal cell-derived factor 1 (SDF-1) in a concentration-dependent and CXCR4 receptor-mediated manner. Here, we demonstrate that CXCR4-binding HIV-1 X4 gp120 causes the movement of T cells, including HIV-specific CTL, away from high concentrations of the viral protein. This migratory response is CD4 independent and inhibited by anti-CXCR4 antibodies and pertussis toxin. Additionally, the expression of X4 gp120 by target cells reduces CTL efficacy in an in vitro system designed to account for the effect of cell migration on the ability of CTL to kill their target cells. Recombinant X4 gp120 also significantly reduced antigen-specific T-cell infiltration at a site of antigen challenge in vivo. The repellant activity of HIV-1 gp120 on immune cells in vitro and in vivo was shown to be dependent on the V2 and V3 loops of HIV-1 gp120. These data suggest that the active movement of T cells away from CXCR4-binding HIV-1 gp120, which we previously termed fugetaxis, may provide a novel mechanism by which HIV-1 evades challenge by immune effector cells in vivo.
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PMID:Migration of antigen-specific T cells away from CXCR4-binding human immunodeficiency virus type 1 gp120. 1511

The membrane fusion events which initiate human immunodeficiency virus type 1 (HIV-1) infection and promote cytopathic syncytium formation in infected cells commence with the binding of the HIV envelope glycoprotein (Env) to CD4 and an appropriate coreceptor. Here, we show that HIV Env-coreceptor interactions activate Rac-1 GTPase and stimulate the actin filament network reorganizations that are requisite components of the cell fusion process. Disrupting actin filament dynamics with jasplakinolide or latrunculin A arrested fusion at a late step in the formation of Env-CD4-coreceptor complexes. Time-lapse confocal microscopy of living cells revealed vigorous activity of actin-based, target cell membrane extensions at the target cell-Env-expressing cell interface. The expression of dominant-negative forms of actin-regulating Rho-family GTPases established that HIV Env-mediated syncytium formation relies on Rac-1 but not on Cdc42 or Rho activation in target cells. Similar dependencies were found when cell fusion was induced by Env expressed on viral or cellular membranes. Additionally, Rac activity was specifically upregulated in a coreceptor-dependent manner in fusion reaction cell lysates. These results define a role for HIV Env-coreceptor interactions in activating the cellular factors essential for virus-cell and cell-cell fusion and provide evidence for the participation of pertussis toxin-insensitive signaling pathways in HIV-induced membrane fusion.
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PMID:Actin cytoskeletal reorganizations and coreceptor-mediated activation of rac during human immunodeficiency virus-induced cell fusion. 1519 90

CC chemokine receptor 5 (CCR5) is a seven-transmembrane, G protein-coupled receptor (GPCR) which regulates trafficking and effector functions of memory/effector T-lymphocytes, macrophages, and immature dendritic cells. It also serves as the main coreceptor for the entry of R5 strains of human immunodeficiency virus (HIV-1, HIV-2). Chemokine binding to CCR5 leads to cellular activation through pertussis toxin-sensitive heterotrimeric G proteins as well as G protein-independent signalling pathways. Like many other GPCR, CCR5 is regulated by agonist-dependent processes which involve G protein coupled receptor kinase (GRK)-dependent phosphorylation, beta-arrestin-mediated desensitization and internalization. This review discusses recent advances in the elucidation of the structure and function of CCR5, as well as the complex mechanisms that regulate CCR5 signalling and cell surface expression.
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PMID:Chemokine receptor CCR5: insights into structure, function, and regulation. 1533 20

Congenital and neonatal viral infections usually display their acute manifestations in highly recognisable ways, for example, congenital rubella, cytomegalovirus (CMV), varicella, human immunodeficiency (HIV) and herpes simplex virus (HSV) infection. By contrast, congenital hepatitis B virus (HBV) infection may go undetected for years. Some of these are preventable, but what is not immediately apparent is that the long-term consequences are being prevented as well. The long-term consequences of congenital and neonatal infections include endocrine, immunological and cardiovascular disease, deafness, visual problems, intellectual handicap and cerebral palsy. With the survival of HIV-infected infants into adulthood the long-term consequences will soon be described. Maternally and neonatally transmitted HBV infection predisposes to carriage, liver cirrhosis and hepatocellular carcinoma in young adults. Neonatal HBV vaccination prevents adult cancer. Acquired viral infections may predispose to subsequent lung disease, malabsorption, fertility problems or neurological disability. In the prevention of acquired rubella, varicella, HBV, influenza, poliovirus, measles and hepatitis A, one should mention the added bonus of preventing secondary cases by preventing transmission from infants and children to other children and adults. Preventing paediatric HSV, HBV and HIV infection in females may even be preventing subsequent transmission to future generations. Turning to paediatric bacterial infections, vaccinating infants and young children against pertussis could not only prevent transmission to older children and adults but also break the cycle, which then transmits from adults back to infants and young children. There is evidence that disease in older age groups, including adults, has been prevented by virtue of herd immunity from paediatric vaccination, e.g. Neisseria meningitidis Group C and Streptococcus pneumoniae. The add-on benefits for other generations, including for adults, arising from the prevention of paediatric infections are considerable.
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PMID:Paediatric infections: prevention of transmission and disease--implications for adults. 1575 76

HIV-Tat, a conserved protein playing a key role in the early life cycle of the human immunodeficiency virus (HIV) has been proposed as a potential AIDS vaccine. An HIV-Tat-based vaccine should elicit a broad, long-lasting, and neutralizing immune response. We have previously demonstrated that the adenylate cyclase (CyaA) from Bordetella pertussis targets dendritic cells and delivers CD8(+) and CD4(+) T-cell epitopes into the major histocompatibility complex class I and class II presentation pathways. We have also showed that CyaA induced specific and protective cytotoxic T cell responses in vivo. Here, we designed a prototype vaccine based on the HIV type 1 Tat delivered by CyaA (CyaA-E5-Tat) and tested its capacity to induce HIV-Tat-specific cellular as well as antibody responses. We showed that immunization of mice by CyaA-E5-Tat in the absence of adjuvant elicited strong and long-lasting neutralizing anti-Tat antibody responses more efficient than those obtained after immunization with Tat toxoid in aluminum hydroxide adjuvant. Analyses of the anti-Tat immunoglobulin G isotypes and the cytokine pattern showed that CyaA-E5-Tat induced a Th1-polarized immune response in contrast to the Th2-polarized immune responses obtained with the Tat toxoid. In addition, our data demonstrated that HIV-Tat-specific gamma interferon-producing CD8(+) T cells were generated after vaccination with CyaA-E5-Tat in a CD4(+) T-cell-independent manner. Based on these findings, CyaA-E5-Tat represents an attractive vaccine candidate for both preventive and therapeutic vaccination involving CyaA as an efficient nonreplicative vector for protein delivery.
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PMID:Induction of neutralizing antibodies and Th1-polarized and CD4-independent CD8+ T-cell responses following delivery of human immunodeficiency virus type 1 Tat protein by recombinant adenylate cyclase of Bordetella pertussis. 1601 48


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