Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interactions of membrane proteins are important in various aspects of cell function. However, weak membrane protein-protein interactions are difficult to study using techniques such as co-immunoprecipitations. CD4 is a cell surface protein involved in T cell activation and the binding of the human immunodeficiency virus to HIV target cells. Here we report the use of cross-linking followed by affinity purification of CD4 in combination with mass spectrometry for identification of proteins that are in the proximity of CD4. Besides the components of the CD4 receptor complex, CD4 and lck, we have identified by tandem mass spectrometry 17 tryptic peptides from transferrin receptor CD71, three peptides from protein phosphatase CD45, and one peptide from 4F2 lymphocyte activation antigen CD98. The efficiency of the cross-linking did not correlate with the level of cell surface expression of the detected molecules, excluding a possible bias of the cross-linking toward the most abundant cell surface molecules. Whereas the association of CD4 with CD45 has been reported, the associations with CD71 and CD98 have not been previously described. We used small-scale immunoprecipitation after cross-linking in combination with fluorescence resonance energy transfer (FRET) measurements to investigate the association between CD4 and CD71. Our data show that CD71 self-associates on the cell surface, that a small fraction of CD4 can be detected by copurifying it with CD71 after cross-linking, and that the level of association between CD4 and CD71 significantly increases after phorbol 12-myristate 13-acetate-induced endocytosis of CD4. This suggests that a small fraction of CD4 associates with clusters of CD71. As both molecules undergo endocytic recycling, the association and cross-linking result from their clustering in the same pit and/or vesicle. The CD4-CD98 association probably results from nonspecific cross-linking.
 ...
PMID:Lateral membrane protein associations of CD4 in lymphoid cells detected by cross-linking and mass spectrometry. 1470 53

The human immunodeficiency virus-1 (HIV-1) envelope glycoprotein 120 (gp120) binds to cell surface receptors and mediates HIV entry. Previous studies suggest the cell surface protein disulfide isomerase (PDI) might interact with disulfide bond(s) of gp120 and thus facilitate HIV-1 entry. In the present study, a kinetic trapping approach was used to capture the disulfide cross-linking intermediate between gp120 and PDI. Active site mutant PDIs were prepared in which the C-terminal cysteine at the active site was replaced by a serine. The active site mutant PDIs were able to covalently cross-link with gp120 through a mixed disulfide bond in vitro. The cross-linking efficiency was enhanced by CD4 protein (primary receptor of HIV-1) and was inhibited both by bacitracin (a PDI inhibitor) and by catalytically inactive PDI. The present results suggested the cell surface PDI might play a role in HIV entry in vivo.
 ...
PMID:Snapshot of the interaction between HIV envelope glycoprotein 120 and protein disulfide isomerase. 2045 50

Human immunodeficiency virus (HIV) infection is associated with insulin resistance. HIV type 1 Nef downregulates cell surface protein expression, alters signal transduction, and interacts with the cytoskeleton and proteins involved in actin polymerization. These functions are required for glucose uptake by insulin-stimulated adipocytes. We sought to determine whether Nef alters adipocyte glucose homeostasis. Using radiolabeled glucose, we found that adipocytes exposed to recombinant Nef took in 42% less glucose after insulin stimulation than did control cells. This reduction resulted from a Nef-dependent inhibition of glucose transporter 4 (GLUT4) trafficking, as assessed by means of immunofluorescence microscopy. Immunoblot analysis revealed a decrease in phosphorylation of signal transducing proteins after Nef treatment, and fluorescence microscopy showed a dramatic alteration in cortical actin organization. We conclude that Nef interferes with insulin-stimulated processes in adipocytes. We have identified HIV Nef, which is detectable and antigenic in serum samples from HIV-infected people, as a novel contributor to the development of insulin resistance.
 ...
PMID:Nef inhibits glucose uptake in adipocytes and contributes to insulin resistance in human immunodeficiency virus type I infection. 2160 41

Dendritic cells (DC) are mediators of the adaptive immune response responsible for antigen presentation to naive T cells in secondary lymph organs. Human immunodeficiency virus (HIV-1) has been reported to inhibit the maturation of DC, but a clear link between maturation and function has not been elucidated. To understand further the effects of HIV-1 on DC maturation and function, we expanded upon previous investigations and assessed the effects of HIV-1 infection on the expression of surface molecules, carbohydrate endocytosis, antigen presentation and lipopolysaccharide (LPS) responsiveness over the course of maturation. In vitro infection with HIV-1 resulted in an increase in the expression of DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) as well as decreases in maturation-induced CCR7 and major histocompatibility complex (MHC)-II expression. Retention of endocytosis that normally occurs with DC maturation as well as inhibition of antigen presentation to CD8(+) T cells was also observed. Mitogen-activated protein kinase (MAPK) responsiveness to LPS as measured by phosphorylation of p38, c-Jun N-terminal kinase (JNK) and extracellular-regulated kinase (ERK)1/2 was not affected by HIV-1 infection. In summary, in-vitro HIV-1 impairs DC maturation, as defined by cell surface protein expression, with selective alterations in mature DC function. Understanding the mechanisms of DC dysfunction in HIV infection will provide further insight into HIV immune pathogenesis.
 ...
PMID:The effect of human immunodeficiency virus-1 on monocyte-derived dendritic cell maturation and function. 2294 6

Human immunodeficiency virus (HIV) preferentially infects and destroys CD4+ cells and leads to a gradual decline in the number of CD4 cells. Despite evidence that probiotics increase CD4+ T lymphocytes in patients with HIV/acquired immunodeficiency syndrome (AIDS) and lower the risk of HIV transmission, little is known about the detailed mechanism underlying these effects. In this study, we investigated the cell surface protein of Lactobacillus and its role in blocking HIV-1 transmission by lactobacilli. Using reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence, and flow cytometry (fluorescence-activated cell sorting, FACS), we detected the CD4 receptor on the surface of Lactobacillus. Monoclonal antibody (mAb) for the CD4 receptor could partially inhibit HIV-1 binding to Lactobacillus. In addition, Lactobacillus could decrease HIV-1 pseudovirus infection of TZM-bl cells in vitro by 60-70%. Our data suggest that Lactobacillus can use this receptor to bind HIV and block HIV infection. This may in turn increase the CD4 T lymphocyte count in patients with HIV. These data provide direct evidence that Lactobacillus expresses the CD4 receptor and utilizes it to block HIV transmission.
 ...
PMID:CD4 detected from Lactobacillus helps understand the interaction between Lactobacillus and HIV. 2331 49


<< Previous 1 2