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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primate lentiviruses use chemokine coreceptors in addition to the CD4 receptor to initiate virus infection. Simian immunodeficiency virus (SIV) productively infects human cells expressing CD4 and the human allele of the chemokine coreceptor CCR-5 as efficiently as it infects macaque cells expressing human CD4, suggesting that SIV can function with either a simian or a human coreceptor in conjunction with human CD4. In the same macaque cells expressing human CD4, the replication of human immunodeficiency virus type 1 (HIV-1) is blocked at several stages of infection; some isolates are restricted prior to reverse transcription, while others, including some macrophage-tropic and primary isolates, are restricted at a step after reverse transcription but prior to migration of the preintegration complex to the nucleus. Both blocks in HIV-1 replication can be relieved by either expression of the appropriate human coreceptor (CCR-5 or CXCR-4) or expression of SIV gene products in cis with the HIV-1 envelope as a chimera between SIV and HIV-1 (SHIV). Thus, a virus with a SIV core and HIV-1 envelope can efficiently infect macaque cells expressing human CD4, presumably by interacting with the simian coreceptor, whereas a virus with an HIV-1 core and an HIV-1 envelope requires expression of the human allele of the coreceptor for productive infection of these cells. These studies suggest that there are interactions among the coreceptor, the viral envelope, and another viral gene product that govern postentry steps of virus replication. These data are consistent with the hypothesis that such interactions may be required for translocation of the virus core to the nucleus. Moreover, the differential abilities of SIV and HIV-1 to function in these processes with heterologous primate coreceptors may have implications for cross-species transmission.
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PMID:Human immunodeficiency virus type 1 coreceptors participate in postentry stages in the virus replication cycle and function in simian immunodeficiency virus infection. 909 70

Certain chemokine receptors serve as cofactors for HIV type 1 envelope (env)-mediated cell-cell fusion and virus infection of CD4-positive cells. Macrophage tropic (M-tropic) HIV-1 isolates use CCR5, and T cell tropic (T-tropic) strains use CXCR4. To investigate the cofactors used by simian immunodeficiency viruses (SIV), we tested four T-tropic and two M-tropic SIV env proteins for their ability to mediate cell-cell fusion with cells expressing CD4 and either human or nonhuman primate chemokine receptors. Unlike HIV-1, both M- and T-tropic SIV envs used CCR5 but not CXCR4 or the other chemokine receptors tested. However, by testing a panel of CCR5/CCR2b chimeras, we found that the structural requirements for CCR5 utilization by M-tropic and T-tropic SIV strains were different. T-tropic SIV strains required the second extracellular loop of CCR5 whereas a closely related M-tropic SIV strain could, like M-tropic HIV-1 strains, use the amino-terminal domain of CCR5. As few as two amino acid changes in the SIV env V3 domain affected the regions of CCR5 that were critical for fusogenic activity. Receptor signaling was not required for either fusion or infection. Our results suggest that viral tropism may be influenced not only by the coreceptors used by a given virus strain but also by how a given coreceptor is used.
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PMID:Differential utilization of CCR5 by macrophage and T cell tropic simian immunodeficiency virus strains. 910 95

Recent findings have shown that the expression of the seven trans-membrane G-protein-coupled CXCR4 (the receptor for the stromal cell-derived factor [SDF]-1 chemokine) is necessary for the entry of T-lymphotropic human immunodeficiency virus (HIV) strains, acting as a coreceptor of the CD4 molecule. In the human system, the role of CXCR4 in HIV infection has been determined through env-mediated cell fusion assays and confirmed by blocking viral entry in CD4+/CXCR4+ cells by SDF-1 pretreatment. We observed that the human megakaryoblastic CD4+ UT-7 cell line fails to express CXCR4 RNA and is fully resistant to HIV entry. Transfection of an expression vector containing the CXCR4 c-DNA rendered UT-7 cells readily infectable by different T-lymphotropic syncytium-inducing HIV-1 and HIV-2 isolates. Interestingly, HIV-1 infection of CXCR4 expressing UT-7 cells (named UT-7/fus) induces the formation of polynucleated cells through a process highly reminiscent of megakaryocytic differentiation and maturation. On the contrary, no morphologic changes were observed in HIV-2-infected UT-7/fus cells. These findings further strengthen the role of CXCR4 as a molecule necessary for the replication of T-lymphotropic HIV-1 and HIV-2 isolates and provide a useful model to study the functional role of CD4 coreceptors in HIV infection.
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PMID:Human immunodeficiency virus (HIV)-resistant CD4+ UT-7 megakaryocytic human cell line becomes highly HIV-1 and HIV-2 susceptible upon CXCR4 transfection: induction of cell differentiation by HIV-1 infection. 910 84

Chemokines are a family of related proteins that regulate leukocyte infiltration into inflamed tissue. Some chemokines such as MIP-1 alpha also inhibit hematopoietic progenitor cell proliferation. Recently, three chemokines, MIP-1 alpha, MIP-1 beta, and RANTES, have been found to significantly decrease human immunodeficiency virus production from infected T cells. We report here the cloning and characterization of a novel human chemokine termed Exodus for its chemotactic properties. This novel chemokine is distantly related to other chemokines (28% homology with MIP-1 alpha) and shares several biological activities. Exodus is expressed preferentially in lymphocytes and monocytes, and its expression is markedly upregulated by mediators of inflammation such as tumor necrosis factor or lipopolysaccharide. Purified synthetic Exodus was found to inhibit proliferation of myeloid progenitors in colony formation assays. Exodus also stimulated chemotaxis of peripheral blood mononuclear cells. The sequence homology, expression, and biological activity indicate that Exodus represents a novel divergent beta-chemokine.
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PMID:Cloning and characterization of exodus, a novel beta-chemokine. 912 37

Syncytium formation is one of major cytopathic effects of human immunodeficiency virus (HIV) infection, and requires the interaction of CD4 molecules on uninfected cells with HIV envelope glycoprotein gp120 expressed on HIV-infected cells. Recent evidence suggests chemokine receptors function as fusion cofactors. We have recently found that fusion regulatory protein (FRP)-1/ CD98 is involved in syncytium formation of HIV gp160-expressing U2ME-7 cells and TALL-1 cells persistently infected with HIV. However, resting lymphocytes were found to express no FRP-1 molecule. In this study, we demonstrated that recombinant gp120 (rpg120) has the ability to induce expression of FRP-1 on peripheral blood mononuclear cells (PBMC). Three-color flow cytometric analysis showed that rgp120-induced FRP-1 was expressed selectively on CD4+ T cells in a dose-dependent manner. FRP-1 expression level was maximum 3 days after addition of rgp120. Anti-CD4 and anti-gp120 antibodies blocked rgp120-induced FRP-1 expression. Co-cultivation of PBMC with HIV-1 gp160-expressing HeLa cells also resulted in the increased expression of FRP-1 on T cells. These results suggest that FRP-1 molecules are induced on CD4+ T cells via CD4-gp120 interaction and may play an important role in regulation of HIV-induced syncytium formation.
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PMID:Human immunodeficiency virus type-1 envelope glycoprotein gp120 induces expression of fusion regulatory protein (FRP)-1/CD98 on CD4+ T cells: a possible regulatory mechanism of HIV-induced syncytium formation. 913 96

CD8+ T-cell clones were generated from peripheral blood mononuclear cells (PBMC) of three human immunodeficiency virus (HIV)-seronegative individuals and six HIV-seropositive individuals and assessed for their cytokine secretion profile, cytolytic potential, and chemokine production. While the great majority of CD8+ T-cell clones generated from HIV-seronegative individuals produced interferon (IFN)-gamma, but not interleukin-4 (IL-4), that is a type 1 cytotoxic (Tc1) profile, high numbers of CD8+ T-cell clones generated from HIV-seropositive individuals produced IL-4 in addition to IFN-gamma or IL-4 alone, thus showing a type 0 cytotoxic (Tc0)- or a type 2 cytotoxic (Tc2) profile, respectively. Tc0/Tc2 cells displayed lower cytolytic activity than Tc1 cells, including a reduced ability to lyse autologous targets pulsed with HIV or HIV peptides. By contrast, the production of chemokines RANTES and macrophage inflammatory protein-1alpha was comparable in Tc1, Tc0, and Tc2 clones irrespective of whether they were derived from HIV-seronegative or HIV-seropositive individuals. When CD8+ T-cell clones were generated from PBMC cultures of HIV-seronegative individuals conditioned with IL-4 plus an anti-IL-12 antibody (Ab), a shift towards the Tc0/Tc2-like profile was observed. Conversely, the addition to PBMC cultures of IL-12 plus an anti-IL-4 Ab shifted the differentiation of CD8+ T cells from HIV-infected individuals towards the Tc1-like profile, whereas IL-12 or anti-IL-4 Ab alone had a lower Tc1-promoting effect. Irradiated PBMC from HIV-infected individuals, used as feeder cells, shifted the differentiation of CD8+ T cells from a healthy HIV-seronegative individual towards the Tc0/Tc2-like profile. On the other hand, a shift towards the Tcl-like profile was noted in CD8+ T-cell clones generated from the skin specimens of two HIV-seropositive patients with Kaposi's sarcoma, successfully treated with IFN-alpha, in comparison to CD8+ clones generated from the same skin areas before treatment. The IFN-alpha-induced Tc1 shift could be prevented by the incubation of skin-infiltrating CD8+ T cells with IL-4 before cloning. Taken together, these data indicate that both defective production of IL-12 and abnormal IL-4 production in bulk PBMC populations of HIV-infected individuals may contribute to the development of high numbers of CD8+ T-cell clones showing a Tc0/Tc2-like phenotype and reduced cytolytic potential against HIV itself. They also suggest that the cytokine profile of CD8+ T-cell clones can be modulated by cytokines (or anticytokine Ab) both in vitro and in vivo.
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PMID:Functional characterization and modulation of cytokine production by CD8+ T cells from human immunodeficiency virus-infected individuals. 916 Jun 72

The human cytomegalovirus encodes a beta-chemokine receptor (US28) that is distantly related to the human chemokine receptors CCR5 and CXCR4, which also serve as cofactors for the entry into cells of human immunodeficiency virus-type 1 (HIV-1). Like CCR5, US28 allowed infection of CD4-positive human cell lines by primary isolates of HIV-1 and HIV-2, as well as fusion of these cell lines with cells expressing the viral envelope proteins. In addition, US28 mediated infection by cell line-adapted HIV-1 for which CXCR4 was an entry cofactor.
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PMID:Identification of a chemokine receptor encoded by human cytomegalovirus as a cofactor for HIV-1 entry. 920 39

The discovery that chemokine receptors are the human cofactors required along with CD4 for fusion and infection by HIV has opened new directions in AIDS research on mechanisms of viral entry, tropism, and pathogenesis. A possible mechanism of co-receptor function has been demonstrated that involves the formation of a complex on the cell surface between the HIV-1 envelope, CD4, and the coreceptor. Functional studies indicate that this interaction is structurally complex, that it probably involves multiple domains of the coreceptor, and that different virus isolates interact with coreceptors in distinct ways. Other immunodeficiency viruses including simian immunodeficiency virus and feline immunodeficiency virus also utilize chemokine receptors for entry. The identification of genetic polymorphisms helps explain why some people, with alterations in the CCR5 gene that prevent expression, are protected from HIV-1 infection. The discovery of specific HIV-1 fusion coreceptor molecules has not only provided new insights into the mechanisms of viral entry and tropism, but also led to new avenues of investigation on strategies to block HIV infection.
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PMID:Chemokine receptors and HIV. 922 88

Several members of the chemokine-receptor family serve, in conjunction with CD4, as receptors for the entry of human immunodeficiency virus type I (HIV-1) into cells. The principal receptor for entry of macrophage-tropic (M-tropic) HIV-1 strains is CCR5, whereas that for T-cell-line-tropic (T-tropic) strains is CXCR4. Unlike HIV-1, infection with either M-tropic or T-tropic strains of simian immunodeficiency virus (SIV) can be mediated by CCR5, but not CXCR4. SIV strains will also infect CD4+ cells that lack CCR5, which suggests that these strains use as yet unidentified receptors. Here we use an expression-cloning strategy to identify SIV receptors and have isolated genes encoding two members of the seven-transmembrane G-protein-coupled receptor family that are used not only by SIVs, but also by strains of HIV-2 and M-tropic HIV-1. Both receptors are closely related to the chemokine-receptor family and are expressed in lymphoid tissues. One of the receptors is also expressed in colon and may therefore be important in viral transmission. Usage of these new receptors following experimental infection of non-human primates with SIV strains may provide important insight into viral transmission and the mechanisms of SIV- and HIV-induced acquired immune-deficiency syndrome.
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PMID:Expression cloning of new receptors used by simian and human immunodeficiency viruses. 923 Apr 27

Clinical isolates of primate immunodeficiency viruses, including human immunodeficiency virus type 1 (HIV-1), enter target cells by sequential binding to CD4 and the chemokine receptor CCR5, a member of the seven-transmembrane receptor family. HIV-1 variants which use additional chemokine receptors are present in the central nervous system or emerge during the course of infection. Simian immunodeficiency viruses (SIV) have been shown to use CCR5 as a coreceptor, but no other receptors for these viruses have been identified. Here we show that two orphan seven-transmembrane segment receptors, gpr1 and gpr15, serve as coreceptors for SIV, and are expressed in human alveolar macrophages. The more efficient of these, gpr15, is also expressed in human CD4(+) T lymphocytes and activated rhesus macaque peripheral blood mononuclear cells. The gpr15 and gpr1 proteins lack several hallmarks of chemokine receptors, but share with CCR5 an amino-terminal motif rich in tyrosine residues. These results underscore the potential diversity of seven-transmembrane segment receptors used as entry cofactors by primate immunodeficiency viruses, and may contribute to an understanding of viral variation and pathogenesis.
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PMID:Two orphan seven-transmembrane segment receptors which are expressed in CD4-positive cells support simian immunodeficiency virus infection. 923 92


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