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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sleep is altered early in the course of HIV infection, before the onset of AIDS, indicating effects of the virus on neural processes. Previous observations suggest HIV envelope glycoproteins are possible mediators of these responses. Because some beta (CC)-chemokine receptors serve as co-receptors for HIV and bind HIV envelope glycoproteins, we determined in this study whether selected CC chemokine ligands alter sleep and whether their mRNAs are detectable in brain regions important for sleep. CCL4/MIP-1beta, but not CCL5/RANTES, injected centrally into rats prior to dark onset increased non-rapid eye movements sleep, fragmented sleep, and induced fever. mRNA for the chemokine receptor CCR3 was detectable under basal conditions in multiple brain regions. These data suggest some CC chemokines may also be involved in processes by which HIV alters sleep.
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PMID:Beta (CC)-chemokines as modulators of sleep: implications for HIV-induced alterations in arousal state. 1158 35

HIV-1 infects target cells via a receptor complex formed by CD4 and a chemokine receptor, primarily CCR5 or CXCR4 (ref. 1). Commonly, HIV-1 transmission is mediated by CCR5-tropic variants, also designated slow/low, non-syncytia-inducer or macrophage-tropic, which dominate the early stages of HIV-1 infection and frequently persist during the entire course of the disease. In contrast, HIV-1 variants that use CXCR4 are typically detected at the later stages, and are associated with a rapid decline in CD4+ T cells and progression to AIDS (refs. 2,7-11). Disease progression is also associated with the emergence of concurrent infections that may affect the course of HIV disease by unknown mechanisms. A lymphotropic agent frequently reactivated in HIV-infected patients is human herpesvirus 6 (HHV-6), which has been proposed as a cofactor in AIDS progression. Here we show that in human lymphoid tissue ex vivo, HHV-6 affects HIV-1 infection in a coreceptor-dependent manner, suppressing CCR5-tropic but not CXCR4-tropic HIV-1 replication, as shown with both uncloned viral isolates and isogenic molecular chimeras. Furthermore, we demonstrate that HHV-6 increases the production of the CCR5 ligand RANTES ('regulated upon activation, normal T-cell expressed and secreted'), the most potent HIV-inhibitory CC chemokine, and that exogenous RANTES mimics the effects of HHV-6 on HIV-1, providing a mechanism for the selective blockade of CCR5-tropic HIV-1. Our data suggest that HHV-6 may profoundly influence the course of HIV-1 infection.
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PMID:Suppression of CCR5- but not CXCR4-tropic HIV-1 in lymphoid tissue by human herpesvirus 6. 1168 88

It is very likely that perinatal human immunodeficiency virus type 1 (HIV-1) infection is influenced by a combination of virologic and host factors. A greater understanding of the role played by various risk factors for HIV-1 infection is crucial for the design of new preventive and therapeutic strategies. In recent years, a number of studies have suggested that host genetic factors are important determinants of both the susceptibility to perinatal HIV-1 infection and the subsequent pathogenesis of acquired immunodeficiency syndrome (AIDS). Control of HIV-1 infection involves the processing of specific viral peptides and their presentation to cells of the immune system by highly polymorphic human leukocyte antigen (HLA) alleles. The contribution of multiple HLA class I and II alleles in modulating pediatric HIV/AIDS outcomes has now been confirmed by several independent groups. Penetration of HIV-1 into cells is mediated by interaction between CD4 and chemokine receptors that serve as entry coreceptors. Genetic polymorphisms in chemokine ligand and chemokine receptor genes have recently been associated both with mother-to-child HIV-1 transmission and disease progression in children. These observations suggest a key role for genetic factors in pediatric HIV-1 infection. This article describes the current state of knowledge regarding host genetic influences on pediatric HIV-1 infection and discusses the role of these genes in HIV/AIDS pathogenesis.
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PMID:Genetic determinants of pediatric HIV-1 infection: vertical transmission and disease progression among children. 1177 47

Kaposi's sarcoma (KS)-associated herpesvirus (KSHV; also called human herpesvirus 8) is believed to be the etiologic agent of Kaposi's sarcoma, multicentric Castleman's disease, and AIDS-associated primary effusion lymphoma. KSHV infection of human dermal microvascular endothelial cells (DMVEC) in culture results in the conversion of cobblestone-shaped cells to spindle-shaped cells, a characteristic morphological feature of cells in KS lesions. All spindle-shaped cells in KSHV-infected DMVEC cultures express the latency-associated nuclear protein LANA1, and a subfraction of these cells undergo spontaneous lytic cycle induction that can be enhanced by tetradecanoyl phorbol acetate (TPA) treatment. To study the cellular response to infection by KSHV, we used two different gene array screening systems to examine the expression profile of either 2,350 or 9,180 human genes in infected compared to uninfected DMVEC cultures in both the presence and absence of TPA. In both cases, between 1.4 and 2.5% of the genes tested were found to be significantly upregulated or downregulated. Further analysis by both standard and real-time reverse transcription-PCR procedures directly confirmed these results for 14 of the most highly upregulated and 13 of the most highly downregulated genes out of a total of 37 that were selected for testing. These included strong upregulation of interferon-responsive genes such as interferon response factor 7 (IRF7) and myxovirus resistance protein R1, plus upregulation of exodus 2 beta-chemokine, RDC1 alpha-chemokine receptor, and transforming growth factor beta3, together with strong downregulation of cell adhesion factors alpha(4)-integrin and fibronectin plus downregulation of bone morphogenesis protein 4, matrix metalloproteinase 2, endothelial plasminogen activator inhibitor 1, connective tissue growth factor, and interleukin-8. Significant dysregulation of several other cytokine-related genes or receptors, as well as endothelial cell and macrophage markers, and various other genes associated with angiogenesis or transformation was also detected. Western immunoblot and immunohistochemical analyses confirmed that the cellular IRF7 protein levels were strongly upregulated during the early lytic cycle both in KSHV-infected DMVEC and in the body cavity-based lymphoma BCBL1 PEL cell line.
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PMID:Altered patterns of cellular gene expression in dermal microvascular endothelial cells infected with Kaposi's sarcoma-associated herpesvirus. 1188 66

Chemokines and their receptors are involved in the pathogenesis of diseases ranging from asthma to AIDS. Chemokine receptors are G-protein-coupled serpentine receptors that present attractive tractable targets for the pharmaceutical industry. It is only ten years since the first chemokine receptor was discovered, and the rapidly expanding number of antagonists holds promise for new medicines to combat diseases that are currently incurable. Here, I focus on the rationale for developing antagonists of chemokine receptors for inflammatory disorders and AIDS, and the accumulating evidence that favours this strategy despite the apparent redundancy in the chemokine system.
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PMID:Chemokine receptors: multifaceted therapeutic targets. 1191 Aug 92

Langerhans cells (LCs) are immature dendritic cells (DCs) that capture antigen in peripheral tissues and migrate to draining lymph nodes, where they reside in the paracortex as interdigitating dendritic cells (IDCs). We studied the effects of simian immunodeficiency virus (SIV) on LCs and IDCs during different stages of infection in monkeys. LCs isolated from monkeys with acute SIV infection or acquired immunodeficiency syndrome (AIDS) underwent normal maturation in vitro, including a switch in chemokine receptor expression from CCR5 to CXCR4 and CCR7. LCs migrated normally from skin in response to contact sensitization in monkeys with acute SIV infection. In contrast, LC migration from skin was markedly impaired during AIDS, associated with a reduction in antigen-bearing DCs in draining lymph nodes. Lymph node IDCs were increased in proportion during acute SIV infection and had an activated phenotype, whereas during AIDS IDCs had significantly lower expression of CD40 and the activation marker CD83. IDCs from monkeys with AIDS were refractory to stimulation with CD40L, demonstrating a functional consequence of decreased CD40 expression. SIV-infected DCs were not identified in lymph nodes or skin of monkeys with AIDS, suggesting an indirect effect of infection on DC populations in vivo. These data indicate that DCs are mobilized to lymph nodes during acute SIV infection, but that during AIDS this process is suppressed, with LC migration and IDC activation being impaired. We conclude that disruption of DC homeostasis may play a role in immunopathology induced by human immunodeficiency virus and suggest that therapeutic strategies targeting DCs may have limited efficacy during AIDS.
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PMID:Disrupted homeostasis of Langerhans cells and interdigitating dendritic cells in monkeys with AIDS. 1192 76

Microglia constitute the primary cell type infected with HIV in the brain and play a major role in viral persistence in the CNS and in the development of AIDS dementia. Lack of a suitable animal model and limitations in the availability of human tissues hinder most HIV/AIDS studies investigating the neuropathogenesis of AIDS dementia. The aims of this study were to determine whether baboon microglia can be productively infected with SIV-HIV (SHIV) recombinant viruses in vitro and whether they express HIV-1 receptors and coreceptors. Our results show the presence of mRNA for CD4, CCR5, and CXCR4 chemokine receptors on baboon microglial cells. Microglia lacked mRNA for the CCR3 chemokine receptor. We also show productive infection of baboon microglial cells by two SHIV isolates, SHIV-KU and SHIV-89.6P, and blockade of the infection with soluble CD4 protein, CCR5, and CXCR4 monoclonal antibodies. This study demonstrating the feasibility of infecting baboon microglia with SHIV isolates is an important first step in using the baboon as an alternative nonhuman primate model to study HIV neuropathogenesis.
AIDS Res Hum Retroviruses 2002 May 20
PMID:Infection of baboon microglia with SIV-HIV recombinant viruses: role of CD4 and chemokine receptors. 1203 85

The detection of replication-competent human immunodeficiency virus type 1 (HIV-1) in infected individuals is integral for studies of viral latency and reservoirs of continuing replication during treatment. We describe a modified coculture method to detect/isolate virus from HIV-1-infected individuals with low or undetectable plasma viral loads. We observed a wide range in CD4 and chemokine receptor concentrations on CD4(+) T cells of HIV-1-uninfected donors. We selected cells from donors who expressed high levels of CCR5 after mitogen stimulation to combine in culture with peripheral blood mononuclear cells of HIV-1-infected individuals. Using this donor-enhanced culture method, viruses were isolated from asymptomatic adults with longterm nonprogressive infection, and children receiving effective highly active antiretroviral therapy, whereas parallel cultures with cells expressing lower levels of CCR5 yielded none. Virus was isolated from an individual for whom all previous attempts using reported methods were unsuccessful. Virus growth from cryopreserved cells from this same individual was detected at multiple sampling time points, including a time point at which a sensitive assay to measure 2-LTR (long terminal repeat) circular forms of the viral genome was negative. This will be a useful technique by which to study viral latency and HIV-1 pathogenesis in adult and pediatric populations.
AIDS Res Hum Retroviruses 2002 May 20
PMID:Enhanced culture method for detection of replication-competent virus in peripheral blood mononuclear cells of HIV type 1-infected individuals. 1203 87

Feline immunodeficiency virus (FIV) is a lentivirus that causes feline acquired immunodeficiency syndrome. Infection can be transmitted experimentally via the vagina and rectum, making the cat a useful model for human immunodeficiency virus (HIV) infection. Some strains of FIV use the CXCR4 chemokine receptor in vitro to gain entry to feline cell lines, thymocytes and peripheral blood leucocytes (PBLs). In this study, the tissue expression of messenger ribonucleic acid (mRNA) encoding the CCR3, CXCR4 and CCR5 receptors was examined by reverse transcriptase polymerase chain reaction (RT-PCR). mRNA encoding each receptor was expressed by two feline T-cell lines (Mya-1 and FeTJ), a feline kidney fibroblast cell line (FKCU) and PBLs. Mesenteric lymph node, colon, rectum, uterus, cervix and vagina all expressed mRNA for CXCR4 and CCR5 whilst only lymph node expressed CCR3 mRNA. In order to locate this receptor mRNA expression, in-situ hybridization studies were performed with DNA probes specific for the chemokine receptor mRNAs. CCR5 and CXCR4 receptor mRNA was expressed by epithelial cells and some lamina propria cells of the colon and rectum. Epithelial cell expression of chemokine receptor mRNA was reduced in intensity towards the base of the crypts. Expression of CXCR4 receptor was also demonstrated immunohistochemically on some lamina propria and intraepithelial cells. The expression of these receptor molecules may be important in mucosal infection with FIV.
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PMID:Expression of chemokine receptors in the feline reproductive tract and large intestine. 1205 77

The polymorphisms within the human genome include several functional variants that cause debilitating inherited diseases. An elevated frequency of some of these deleterious mutations can be explained by a beneficial effect that confers a selective advantage owing to disease resistance in carriers of such mutations during an infectious disease outbreak. We here review plausible examples of balanced functional polymorphisms and their roles in the defense against pathogens. The genome organization of the chemokine receptor and HLA gene clusters and their influence on the HIV/AIDS epidemic provides compelling evidence for the interaction of infectious and genetic diseases in recent human history.
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PMID:Balanced polymorphism selected by genetic versus infectious human disease. 1214 57


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