Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was performed to quantitate and characterize the mononuclear phagocytes (MPs) in human immunodeficiency virus encephalopathy (HIVE) by immunohistochemistry in an effort to gain insights into potential mechanisms of central nervous system (CNS) accumulation. Single- and double-labeled studies using antibodies against CD14, CD16, CD68, proliferating cell nuclear antigen (PCNA), Ki-67, von Willebrand factor, and HIV-1 p24 were performed using brain tissue from patients with HIVE, HIV-1 infection without encephalitis, and seronegative controls. A substantial increase in MPs was observed in CNS tissue from patients with HIVE, relative to seronegative controls and patients with acquired immune deficiency syndrome but without encephalitis, as determined by CD68 and CD16 immunohistochemistry. A large proportion of CD16+ MPs in HIVE CNS tissue were PCNA+, but do not appear to be proliferating, based on limited Ki-67 positivity. Although virtually all cells positive for HIV-1 p24 were PCNA+, there were many PCNA+ cells where HIV-1 p24 expression was not detected. PCNA positivity was also observed in some endothelial cells and ependymal cells in HIVE CNS. Our results would support a role for HIV-1-induced alterations in MP trafficking and homeostasis in the pathogenesis of HIVE.
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PMID:Macrophage/microglial accumulation and proliferating cell nuclear antigen expression in the central nervous system in human immunodeficiency virus encephalopathy. 1516 43

CD16+ monocytes represent 5-10% of circulating monocytes in healthy individuals and are dramatically expanded in several pathological conditions including AIDS and HIV-1-associated dementia (HAD). CD16+ monocytes constitutively produce high levels of pro-inflammatory cytokines and neurotoxic factors that may contribute to the pathogenesis of these disorders. Monocyte recruitment into the central nervous system (CNS) and other peripheral tissues in response to locally produced chemokines is a critical event in immune surveillance and inflammation and involves monocyte arrest onto vascular beds and subsequent diapedesis. Here we investigate the ability of CD16+ monocytes to undergo transendothelial migration (TEM) under constitutive and inflammatory conditions. CD16+ monocytes underwent TEM across unstimulated human umbilical vascular (HUVEC) and brain microvascular endothelial (BMVEC) cell monolayers in response to soluble fractalkine (FKN/CX3CL1). Stimulation with tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma) induced high and low expression of membrane-bound FKN on HUVEC and BMVEC, respectively, together with expression of VCAM-1 and intercellular adhesion molecule-1 (ICAM)-1. By contrast, only HUVEC expressed CD62E while BMVEC remained negative. Both CD16- and CD16+ monocyte subsets adhered to TNF/IFN-gamma-stimulated HUVEC with higher frequency than to unstimulated HUVEC. Monocyte chemoattractant protein-1 (MCP-1) triggered efficient TEM of CD16- monocytes across TNF/IFN-gamma-stimulated HUVEC, whereas soluble FKN failed to induce TEM of CD16+ monocytes across stimulated HUVEC. These results demonstrate that stimulation with TNF and IFN-gamma triggers expression of membrane-bound FKN on both HUVEC and BMVEC, but prevents TEM of CD16+ monocytes in response to soluble FKN. Thus, pro-inflammatory CD16+ monocytes may contribute to the pathogenesis of HAD and other inflammatory CNS diseases by affecting the integrity of the blood-brain barrier as a consequence of their massive accumulation onto inflamed brain vascular endothelial cells expressing FKN and other adhesion molecules.
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PMID:Transendothelial migration of CD16+ monocytes in response to fractalkine under constitutive and inflammatory conditions. 1548 Nov 36

Human immunodeficiency virus type 1 (HIV-1)-infected monocytes trafficking into the central nervous system are a risk factor for HIV-1-associated dementia. We performed global gene expression analysis on CD14+ monocytes isolated from HIV-1-infected individuals and controls to identify HIV-1-related changes in monocyte phenotype. Monocytes from subjects with high viral load (HVL) had a significant increase in monocytes expressing CD16, CCR5, and MCP-1. There was also an increase in sialoadhesin, a macrophage marker of chronic inflammation. Expression of proinflammatory cytokine genes IL-1, IL-6, and TNF-alpha was unchanged in individuals with HIV-1 compared to control CD14+ monocytes. Differential gene expression identified by DNA microarray analysis was confirmed with reverse transcription polymerase chain reaction (RT-PCR), while increased protein expression was characterized by immunofluorescence. We concluded that there is a circulating CD14+ macrophage hybrid phenotype in subjects with HVL.
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PMID:Invasive chronic inflammatory monocyte phenotype in subjects with high HIV-1 viral load. 1557 85

Natural killer (NK) cells play an important role in both innate and adaptive antiviral immune responses. The adaptive response typically requires that virus-specific antibodies decorate infected cells which then direct NK cell lysis through a CD16 mediated process termed antibody-dependent cellular cytotoxicity (ADCC). In this report, we employ a highly polymerized chimeric IgG1/IgA immunoglobulin (Ig) fusion protein that, by virtue of its capacity to extensively crosslink CD16, activates NK cells while directing the lysis of infected target cells. We employ HIV as a model system, and demonstrate that freshly isolated NK cells preloaded with an HIV gp120-specific chimeric IgG1/IgA fusion protein efficiently lyse HIV-infected target cells at picomolar concentrations. NK cells pre-armed in this manner retain the capacity to kill targets over an extended period of time. This strategy may have application to other disease states including various viral infections and cancers.
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PMID:Targeted lysis of HIV-infected cells by natural killer cells armed and triggered by a recombinant immunoglobulin fusion protein: implications for immunotherapy. 1568 Apr 14

Natural killer (NK) cells are an important component of the innate immune response against viral infections. NK cell-mediated cytolytic activity is defective in HIV-infected individuals with high levels of viral replication. In the present study, we examined the phenotypic and functional characteristics of an unusual CD56(-)/CD16(+) (CD56(-)) NK subset that is greatly expanded in HIV-viremic individuals. The higher level of expression of inhibitory NK receptors and the lower level of expression of natural cytotoxicity receptors observed in the CD56(-) NK fraction compared with that of CD56(+) NK cells was associated with extremely poor in vitro cytotoxic function of this subset. In addition, the secretion of certain cytokines known to be important in initiating antiviral immune responses was markedly reduced in the CD56(-), as compared with the CD56(+) NK cell subset. These data suggest that the expansion of this highly dysfunctional CD56(-) NK cell subset in HIV-viremic individuals largely accounts for the impaired function of the total NK cell population.
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PMID:Characterization of CD56-/CD16+ natural killer (NK) cells: a highly dysfunctional NK subset expanded in HIV-infected viremic individuals. 1569 23

The aim of this study was to test the effects of drug abuse, in particular opiate abuse, on the phenotype and turnover of microglial cells within the brain in the context of advancing HIV infection. Basal ganglia and hippocampus sections were studied in 51 cases divided into six groups: HIV-negative normal controls, HIV-negative drug abusers, AIDS nondrug abusers, AIDS drug abusers, HIV encephalitis (HIVE) nondrug abusers and HIVE drug abusers. None of the cases studied had received highly active anti-retroviral therapy (HAART). Microglial phenotypes were defined using CD14, CD16, CD68 and major histocompatibility class II (MHC II). Microglial turnover was assessed using terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) (DNA damage), BAX (proapoptotic marker), Fas (CD95) (proapoptotic), proliferating cell nuclear antigen (PCNA) (proliferation and DNA repair), Ki-67 (cell proliferation) and BCL-2 (antiapoptosis). We find increased expression of MHC II and CD16 in response to drug abuse. We also noted increased levels of TUNEL positivity in drug abusers compared to nondrug abusers, although conversely we found lower levels of BAX in those who had abused drugs. We find no evidence of microglial proliferation in any of our study groups, including HIVE, although HIV infection leads to increased expression of CD16, CD68 and MHC II. CD14 expression was restricted to perivascular microglia in all groups (including normal controls) apart from the two HIVE groups where some but not all cases also showed parenchymal expression of CD14. In contrast, CD16 was found in parenchymal microglia in all groups. Using high-pressure antigen retrieval and tyramide signal amplification, we find moderately high levels of CD16 expression in the parenchyma of normal brains which is not normally observed using standard avidin/biotin complex (ABC) techniques. This suggests that a low basal expression of CD16 occurs in many resident microglial cells which may potentially be upregulated in HIV-infected individuals. From these data, we suggest that not all the CD16+ parenchymal cells detected in AIDS brains (using ABC) represent influx of monocyte lineage cells from the blood. Finally the increased expression of MHC II and CD68 detected in drug abusers with HIVE compared to nondrug abusers with HIVE suggests that the combination of drug abuse and HIV infection has a greater deleterious effect on the brain than either individual insult on its own.
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PMID:Does drug abuse alter microglial phenotype and cell turnover in the context of advancing HIV infection? 1588 69

Natural killer (NK) cells are critical in the first-line defense against viral infections. Chronic HIV-1 infection leads to a perturbation in the NK cell compartment, yet the kinetics of this deregulation and the functional consequences are unclear. Here, we characterized changes in the NK cell compartment longitudinally by multiparameter flow cytometry, starting in acute HIV-1 infection. Acute HIV-1 infection was associated with elevated NK cell numbers, with an expansion of CD3(neg)CD56(dim)CD16(pos) NK cells and an early depletion of CD3(neg)CD56(bright)CD16(neg) NK cells. Ongoing viral replication resulted in a depletion of CD3(neg)CD56(dim)CD16(pos) NK cells with a paralleled increase in functionally anergic CD3(neg)CD56(neg)CD16(pos) NK cells, accompanied by reduced functional activity, as measured by CD107a expression and cytokine secretion. Taken together, these studies demonstrate a sequential impairment of NK cell function with persistent viral replication resulting from a progressive deregulation of NK cell subsets with distinct functional properties.
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PMID:Sequential deregulation of NK cell subset distribution and function starting in acute HIV-1 infection. 1600 29

Monocytes play an important, yet only partly understood, role in HIV-1 pathogenesis. Two main subsets of peripheral blood monocytes have been described; the major subset of monocytes are phenotypically characterized as being CD14hi/CD16-, and a minor subset (5-15% of total monocytes in healthy individuals), which are CD14lo/CD16hi, have been reported to be expanded in HIV-infected individuals. These CD14lo/CD16hi monocytes differ from the majority of monocytes in a number of ways, including the molecules expressed on their surface and how they function. Here we describe a flow-cytometric assay to identify and compare the expression of a representative surface molecule (CCR5) on CD14hi/CD16- and CD14lo/CD16hi monocytes in small volumes of whole blood, and methods to isolate monocyte subsets by both fluorescence-activated cell sorting (FACS) and magnetic bead sorting.
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PMID:Phenotypic characterization of blood monocytes from HIV-infected individuals. 1606 88

Peripheral blood CD16 (Fc receptor for immunoglobulin G III)-positive monocytes have been shown to expand in different pathological conditions, such as cancer, asthma, sepsis, human immunodeficiency virus infection, and AIDS progression, but data in leishmaniasis are lacking. We found that cutaneous leishmaniasis patients (n = 15) displayed a significant increase in the percentage (3.5 vs. 10.1) as well as mean fluorescent intensity (13.5 vs. 29.2) of ex vivo CD16 expression in monocytes as compared with healthy controls. We observed a significant positive correlation between the percentage of ex vivo CD16+ monocytes and lesion size (P = 0.0052, r = 0.75) or active transforming growth factor-beta plasma levels (P = 0.0017, r = 0.78). In addition, two patients with nonhealing lesions during a 3-year follow-up had high (9.1-19.4%) CD16 levels at diagnosis. Our data suggest a deleterious role for CD16 in human leishmaniasis, as well as its possible use as a marker for disease severity and/or adverse disease outcome.
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PMID:CD16+ monocytes in human cutaneous leishmaniasis: increased ex vivo levels and correlation with clinical data. 1628 34

The CD16+ subset of monocytes is dramatically expanded in peripheral blood during progression to AIDS, but its contribution to HIV pathogenesis is unknown. Here, we demonstrate that CD16+ but not CD16- monocytes promote high levels of HIV replication upon differentiation into macrophages and interaction with T cells. Conjugates formed between CD16+ monocyte-derived macrophages and T cells are major sites of viral replication. Furthermore, similar monocyte-T cell conjugates detected in peripheral blood of HIV-infected patients harbor HIV DNA. Thus, expansion of CD16+ monocytes during HIV infection and their subsequent recruitment into tissues such as lymph nodes, brain, and intestine may contribute to HIV dissemination and establishment of productive infection in T cells.
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PMID:CD16+ monocytes exposed to HIV promote highly efficient viral replication upon differentiation into macrophages and interaction with T cells. 1630 4


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