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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HIV infection is characterized by the reduction of the CD4+, CD45RA+, CD26+, and CD28+ lymphocyte subsets and of the in vitro production of IL-2, IL-4, and interferon-gamma; on the contrary, chemokine production is usually increased. These abnormalities are only partially restored by antiretroviral chemotherapy. Therapy with interleukin-2 has been proposed to restore the functions of the immune system, but the mechanisms by which IL-2 exerts its activities are unknown. The aim of this study was to define the effects of rIL-2 administration on CD4+, CD45RA+, CD45R0+, and CD26+ lymphocytes and on the in vitro production of IL-2, IL-4, IL-10, IFN-gamma, RANTES, and sCD30 in HIV+ patients. 10 HIV+ patients with CD4 cell counts between 200 and 500 cells/mm3 were treated with six cycles of subcutaneous recombinant IL-2 administration, in combination with zidovudine and didanosine. This therapeutic regimen resulted in a remarkable increase in the number of CD4+ cells and in the prolonged reduction of the levels of viremia. CD45R01 cells were expanded during the first cycle of therapy, while CD45RA+/CD26+ cells predominated after the third cycle. At this time, the in vitro production of IL-2, IL-4, IFN-gamma, and sCD30 were significantly upregulated. These results demonstrate that rIL-2 in HIV+ patients induces the reconstitution of the CD4/CD45RA lymphocytes subtype. This expanded cell population recovered the ability to produce in vitro IL-2, IL-4, and IFN-gamma. These effects may be beneficial to HIV+ patients by improving their immune response to microorganisms or vaccines.
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PMID:Effects of subcutaneous interleukin-2 therapy on CD4 subsets and in vitro cytokine production in HIV+ subjects. 938 37

The CCR5 gene encodes a cell-surface chemokine-receptor molecule that serves as a coreceptor for macrophage-tropic strains of HIV-1. Mutations in this gene may alter expression or function of the protein product, thereby altering chemokine binding/signaling or HIV-1 infection of cells that normally express CCR5 protein. Indeed, homozygotes for a 32-bp deletion allele of CCR5 (CCR5-delta 32), which causes a frameshift at amino acid 185, are relatively resistant to HIV-1 infection. Here we report the identification of 16 additional mutations in the coding region of the CCR5 gene, all but 3 of which are codon altering or "nonsynonymous." Most mutations were rare (found only once or twice in the sample); five were detected exclusively among African Americans, whereas eight were observed only in Caucasians. The mutations included 11 codon-altering nonsynonymous variants, one trinucleotide deletion, one chain-termination mutant, and three synonymous mutations. The high predominance of codon-altering alleles among CCR5 mutants (14/17 [81%], including CCR5-delta 32) is consistent with an adaptive accumulation of function-altering alleles for this gene, perhaps as a consequence of historic selective pressures.
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PMID:Novel alleles of the chemokine-receptor gene CCR5. 939 3

Brain capillary endothelial cells (BCECs) are targets of CD4-independent infection by HIV-1 and simian immunodeficiency virus (SIV) strains in vitro and in vivo. Infection of BCECs may provide a portal of entry for the virus into the central nervous system and could disrupt blood-brain barrier function, contributing to the development of AIDS dementia. We found that rhesus macaque BCECs express chemokine receptors involved in HIV and SIV entry including CCR5, CCR3, CXCR4, and STRL33, but not CCR2b, GPR1, or GPR15. Infection of BCECs by the neurovirulent strain SIV/17E-Fr was completely inhibited by aminooxypentane regulation upon activation, normal T cell expression and secretion in the presence or absence of ligands, but not by eotaxin or antibodies to CD4. We found that the envelope (env) proteins from SIV/17E-Fr and several additional SIV strains mediated cell-cell fusion and virus infection with CD4-negative, CCR5-positive cells. In contrast, fusion with cells expressing the coreceptors STRL33, GPR1, and GPR15 was CD4-dependent. These results show that CCR5 can serve as a primary receptor for SIV in BCECs and suggest a possible CD4-independent mechanism for blood-brain barrier disruption and viral entry into the central nervous system.
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PMID:CD4-independent, CCR5-dependent infection of brain capillary endothelial cells by a neurovirulent simian immunodeficiency virus strain. 940 83

Host factors play an important role in determining rates of disease progression in human immunodeficiency virus (HIV)-infected individuals. HIV is able to subvert the host immune system by infecting CD4+ T cells that normally orchestrate immune responses and by inducing the secretion of proinflammatory cytokines that the virus can utilize to its own replicative advantage. The recognition that certain chemokine receptors serve as necessary co-factors for HIV entry into its target cells as well as the fact that ligands for these receptors can modulate the efficiency of HIV infection has expanded the number and scope of host factors that may impact the pathogenesis of HIV disease. This area of investigation will no doubt yield novel therapeutic strategies for intervention in HIV disease; however, caution is warranted in light of the enormous complexity of the pleiotropic cytokine and chemokine networks and the uncertainty inherent in manipulating these systems. HIV-infected long-term non-progressors represent an excellent model to study potential host factors involved in HIV disease pathogenesis. Genetic factors certainly have a major impact on the immune responses mounted by the host. In this regard, a polymorphism in the gene for the HIV co-receptor CC chemokine receptor 5 (CCR5), which serves as a co-receptor for macrophage (M)-tropic strains of HIV, affords a high degree of protection against HIV infection in individuals homozygous for the genetic defect and some degree of protection against disease progression in HIV-infected heterozygotes. HIV-specific immune responses, including cytotoxic T-lymphocyte (CTL) responses and neutralizing antibody responses, also appear to play salutary roles in protecting against disease progression.
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PMID:Host factors in the pathogenesis of HIV disease. 941 1

Using a chemokine receptor model based on known receptor sequences, we identified several members of the seven transmembrane domain G-protein superfamily as potential chemokine receptors. The orphan receptor ChemR1, which has recently been shown to be a receptor for the CC chemokine I-309, scored very high in our model. We have confirmed that I-309, but not a number of other chemokines, can induce a transient Ca2+ flux in cells expressing CCR8. In addition, the human erythroleukemic cell line K562 responded chemotactically in a dose-responsive manner to this chemokine. Since several chemokine receptors have been shown to be required as coreceptors for HIV-1 infection, we asked whether human immunodeficiency virus type 1 (HIV-1) could efficiently utilize CCR8. Here we show that the CCR8 receptor can serve as a coreceptor for diverse T-cell tropic, dual-tropic, and macrophage-tropic HIV-1 strains and that I-309 was a potent inhibitor of HIV-1 envelope-mediated cell-cell fusion and virus infection. Furthermore, we show by flow cytometry and immunohistochemistry that antibodies generated against the CCR8 receptor amino-terminal peptide cross-reacted with U-87 MG cells stably expressing CCR8, THP-1 cells, HL-60 cells, and human monocytes, a target cell for HIV-1 infectivity in vivo.
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PMID:The CC chemokine I-309 inhibits CCR8-dependent infection by diverse HIV-1 strains. 941 93

To investigate the role played by chemokines in the natural history of human immunodeficiency virus (HIV) infection, we measured the plasma levels of RANTES. MIP-1 alpha and MIP-1 beta in a cohort of patients with primary HIV-1 infection (PHI) followed longitudinally. The cohort included 17 patients with well-documented history of acute HIV syndrome within two months of the first observation. The mean plasma concentration of RANTES, but not that of MIP-1 alpha or MIP-1 beta, was significantly higher in patients with PHI (192.3 ng/ml) than in five HIV-seronegative controls (8.0 ng/ml) studied during the same time period. Treatment of blood with a cocktail of drugs preventing platelet activation, followed by high-speed centrifugation, reduced the levels of RANTES by approximately 2 logs both in patients and in controls, indicating that the bulk of RANTES was released by platelets, which are known to store this chemokine in their alpha-granules, in the immediate aftermath of blood drawing. No correlation was seen between the levels of RANTES and the number of HIV genome equivalents in plasma. These data suggest that large amounts of pre-formed RANTES are stored in platelets and, possibly, in other blood cells during the early phases of HIV infection. The possible role of this HIV-suppressive chemokine in the control of viral replication during PHI remains to be established.
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PMID:Increased plasma levels of the C-C chemokine RANTES in patients with primary HIV-1 infection. 941 60

Over the past few years, considerable technical effort has been directed to developing molecular methods that would allow an effective approach to the diagnosis of human immunodeficiency virus type 1 (HIV-1) infection and its monitoring. Indeed, quantitative molecular techniques have opened the way for a new type of direct study of untreated and treated HIV-1 infected subjects. The understanding of the immunopathogenesis of HIV-1 infection has increased significantly with the introduction of advanced virological and molecular methods for accurate quantitative analysis of HIV-1 activity; powerful methodologies answer (directly and in real time) most questions generated by pathogenic research and by the novel anti-viral strategies introduced in clinical practice. The data from pilot diagnostic applications of quantitative techniques have clarified important features of the natural history of HIV-1 infection. Moreover, an increasing amount of data indicate the need for second-level laboratory facilities for the clinical management of infected patients; virological aspects and some genetic features of the hosts concerning HIV-1 co-receptors (all the co-receptors so far identified are members of, or related to, the transmembrane, chemokine-receptor family) need to be elucidated for the complete diagnostic evaluation of HIV-1-infected subjects.
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PMID:Molecular monitoring of human immunodeficiency virus type 1 infection. 941 66

We have studied the breadth and potency of the inhibitory actions of the CC chemokines macrophage inhibitory protein 1alpha (MIP-1alpha), MIP-1beta, and RANTES against macrophage-tropic (M-tropic) primary isolates of human immunodeficiency virus type 1 (HIV-1) and of the CXC chemokine stromal cell-derived factor 1alpha against T-cell-tropic (T-tropic) isolates, using mitogen-stimulated primary CD4+ T cells as targets. There was considerable interisolate variation in the sensitivity of HIV-1 to chemokine inhibition, which was especially pronounced for the CC chemokines and M-tropic strains. However, this variation was not obviously dependent on the genetic subtype (A through F) of the virus isolates. Peripheral blood mononuclear cell donor-dependent variation in chemokine inhibition potency was also observed. Among the CC chemokines, the rank order for potency (from most to least potent) was RANTES, MIP-1beta, MIP-1alpha. Some M-tropic isolates, unexpectedly, were much more sensitive to RANTES than to MIP-1beta, whereas other isolates showed sensitivities comparable to those of these two chemokines. Down-regulation of the CCR5 and CXCR4 receptors occurred in cells treated with the cognate chemokines and probably contributes to anti-HIV-1 activity. Thus, for CCR5, the rank order for down-regulation was also RANTES, MIP-1beta, MIP-1alpha.
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PMID:Genetic subtype-independent inhibition of human immunodeficiency virus type 1 replication by CC and CXC chemokines. 942 Feb 38

Primary macrophages are infected by macrophage (M)-tropic but not T-cell line (T)-tropic human immunodeficiency virus type 1 (HIV-1) strains, and CCR5 and CXCR-4 are the principal cofactors utilized for CD4-mediated entry by M-tropic and T-tropic isolates, respectively. Macrophages from individuals homozygous for an inactivating mutation of CCR5 are resistant to prototype M-tropic strains that depend on CCR5 but are permissive for a dual-tropic isolate, 89.6, that can use both CCR5 and CXCR-4, as well as CCR2b, CCR3, and CCR8. Here we show that 89.6 entry into CCR5-deficient macrophages is blocked by an anti-CXCR-4 antibody and by the CXCR-4-specific chemokine SDF but not by the ligands to CCR2b or CCR3. Reverse transcription-PCR demonstrated expression of CXCR-4 but not CCR3 or CCR8 in macrophages, while CCR2b was variable. Macrophage surface expression of CXCR-4 was confirmed by immunofluorescence staining and flow cytometry. Thus, CXCR-4 is expressed by primary macrophages and functions as a cofactor for entry by dual-tropic but not T-tropic HIV-1 isolates, and macrophage resistance to T-tropic strains does not result from a lack of the T-tropic entry cofactor CXCR-4. Since CXCR-4 on macrophages can be used by some but not other isolates, these results indicate that HIV-1 strains differ in how they utilize chemokine receptors as cofactors for entry and that the ability of a chemokine receptor to mediate HIV-1 entry differs, depending on the cell type in which it is expressed.
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PMID:CXCR-4 is expressed by primary macrophages and supports CCR5-independent infection by dual-tropic but not T-tropic isolates of human immunodeficiency virus type 1. 942 Feb 85

The chemokine receptor CCR5 and to a lesser extent CCR3 and CCR2b have been shown to serve as coreceptors for human immunodeficiency virus type 1 (HIV-1) entry into blood- or tissue-derived macrophages. Therefore, we examined the expression of the chemokine receptors CCR1, CCR2b, CCR3, CCR5, and CXCR4 as RNAs or as membrane-expressed antigens in monocytes maturing into macrophages and correlated these results with the susceptibility of macrophages to HIV-1 infection, as measured by their concentrations of extracellular p24 antigen and levels of intracellular HIV DNA by quantitative PCR. There was little change in levels of CCR1, CCR2b, and CCR5 RNAs. CCR3 RNA and surface antigen were undetectable throughout maturation of adherent monocytes over 10 days. CXCR4 RNA and membrane antigen were strongly expressed in newly adherent monocytes, but their levels declined at day 7. The amounts of CCR5 RNA remained stable, but the amounts of CCR5 antigen increased from undetectable to peak levels at day 7 and then declined slightly at day 10. Levels of susceptibility to laboratory (HIV-1BaL) and clinical strains of HIV-1 showed parallel kinetics, peaking at day 7 and then decreasing at days 10 to 14. The concordance of levels of HIV DNA and p24 antigen suggested that the changes in susceptibility with monocyte maturation were at or immediately after entry and correlated well with CCR5 expression and inversely with CXCR4 expression.
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PMID:CCR5 expression correlates with susceptibility of maturing monocytes to human immunodeficiency virus type 1 infection. 942 Feb 95


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