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41.
CD4 down-modulation by human immunodeficiency virus type 1 Nef correlates with the efficiency of viral replication and with CD4(+) T-cell depletion in human lymphoid tissue ex vivo 下载免费PDF全文
Glushakova S Münch J Carl S Greenough TC Sullivan JL Margolis L Kirchhoff F 《Journal of virology》2001,75(21):10113-10117
The human immunodeficiency virus type 1 (HIV-1) Nef protein is an important virulence factor. Nef has several functions, including down-modulation of CD4 and class I major histocompatibility complex cell surface expression, enhancement of virion infectivity, and stimulation of viral replication in peripheral blood mononuclear cells. Nef also increases HIV-1 replication in human lymphoid tissue (HLT) ex vivo. We analyzed recombinant and primary nef alleles with highly divergent activity in different in vitro assays to clarify which of these Nef activities are functionally linked. Our results demonstrate that Nef activity in CD4 down-regulation correlates significantly with the efficiency of HIV-1 replication and with the severity of CD4(+) T-cell depletion in HLT. In conclusion, HIV-1 Nef variants with increased activity in CD4 down-modulation would cause severe depletion of CD4(+) T cells in lymphoid tissues and accelerate AIDS progression. 相似文献
42.
Carlum Shiu Coleen K. Cunningham Thomas Greenough Petronella Muresan Victor Sanchez-Merino Vincent Carey J. Brooks Jackson Carrie Ziemniak Lawrence Fox Marvin Belzer Stuart C. Ray Katherine Luzuriaga Deborah Persaud and the Pediatric AIDS Clinical Trials Group P Team 《Journal of virology》2009,83(19):9731-9742
43.
Gabriel Castrillo Eduardo Sánchez-Bermejo Laura de Lorenzo Pedro Crevillén Ana Fraile-Escanciano Mohan TC Alfonso Mouriz Pablo Catarecha Juan Sobrino-Plata Sanna Olsson Yolanda Leo del Puerto Isabel Mateos Enrique Rojo Luis E. Hernández Jose A. Jarillo Manuel Pi?eiro Javier Paz-Ares Antonio Leyva 《The Plant cell》2013,25(8):2944-2957
44.
Methylmethacrylate (MMA) is the most commonly used embedding medium for sectioning undecalcified bone; however, a number of problems exist with its use in a research laboratory. MMA requires a long infiltration time and temperature control, and it reacts with many polymers. We used Kleer Set resin? as an alternative embedding medium for sectioning undecalcified bone specimens. Fluorochrome labeled bone specimens were sectioned transversely using a ground section technique and longitudinally on a sledge macrotome. The slides were viewed using both transmitted light and epifluorescence microscopy. High quality sections were obtained using Kleer Set resin? for both sectioning techniques. We have shown that this new embedding medium is simpler, safer, quicker to use and does not interfere with visualization of fluorochromes. 相似文献
45.
Data on allele frequencies at six red cell blood group systems and three blood protein polymorphic loci in five goat breeds are reported. Two blood proteins, albumin and carbonic anhy-drase, were not found to be polymorphic. The B blood group system of goats, like its homologue in cattle and sheep, is highly complex. At least 44 B phenogroups (haplotypes) have been distinguished in this study. Based on the variation in allele frequencies between breeds, genetic distances were calculated. The distances estimated by four different methods were in close agreement with data from the history and geographic origins of the breeds examined. 相似文献
46.
Adenyl cyclase in human platelets: activity and responsiveness 总被引:7,自引:0,他引:7
A clinical study was conducted whereby the activity of adenyl cyclase in the human platelet was demonstrated. The study showed that this activity can be stimulated and inhibited in vitro. Platelets were isolated from normal donors. The laboratory procedures involved in the study are described in detail. It seems that many of the biologic processes which occur in the human platelet are dependent on the breakdown of ATP (adenosine-tri-phosphate) to, among other substances, AMP (adenosine-3',5' monophosphate). Activity of the adenyl cyclase was stimulated by fluoride, prostaglandin E1, and glucagon; it was inhibited by thrombin, epinephrine, norepinephrine, and serotonin. PG (prostaglandin) E1 at concentrations of 20 ng/ml and above increased adenyl cyclase in 7 experiments by 3-5 times. Even at concentrations as low as 2 ng/ml., PGE2 caused perceptable stimulation. The PGE, while stimulating adenyl cyclase activity, also inhibited aggregation of platelets by a variety of substances. Results of the study suggest that adenosine-3',5' monophosphate may be important in the regulation of platelet adhesiveness. 相似文献
47.
48.
Du T La Fontaine SL Abdo M Bellingham SA Greenough M Volitakis I Cherny RA Bush AI Hudson PJ Camakaris J Mercer JF Crouch PJ Masters CL Perreau VM White AR 《Proteomics》2008,8(9):1819-1831
Neurodegenerative illnesses are characterized by aberrant metabolism of biometals such as copper (Cu), zinc (Zn) and iron (Fe). However, little is known about the metabolic effects associated with altered metal homeostasis. In this study, we used an in vitro model of altered Cu homeostasis to investigate how Cu regulates cellular protein expression. Human fibroblasts containing a natural deletion mutation of the Menkes (MNK) ATP7A Cu transporter (MNK deleted) were compared to fibroblasts overexpressing ATP7A (MNK transfected). Cultures of MNK-transfected (Low-Cu) cells exhibited 95% less intracellular Cu than MNK-deleted (High-Cu) cells. Comparative proteomic analysis of the two cell-lines was performed using antibody microarrays, and significant differential protein expression was observed between Low-Cu and High-Cu cell-lines. Western blot analysis confirmed the altered protein expression of Ku80, nexilin, L-caldesmon, MAP4, Inhibitor 2 and DNA topoisomerase I. The top 50 altered proteins were analysed using the software program Pathway Studio (Ariadne Genomics) and revealed a significant over-representation of proteins involved in DNA repair and maintenance. Further analysis confirmed that expression of the DNA repair protein Ku80 was dependent on cellular Cu homeostasis and that Low-Cu levels in fibroblasts resulted in elevated susceptibility to DNA oxidation. 相似文献
49.
Swingler S Zhou J Swingler C Dauphin A Greenough T Jolicoeur P Stevenson M 《Cell host & microbe》2008,4(1):63-76
B lymphocyte hyperactivation and elevated immunoglobulin levels (hypergammaglobulinemia) are pathogenic manifestations of HIV-1 infection. Here we provide evidence that these hallmarks are caused by a soluble factor whose production by infected macrophages is induced by the HIV-1 Nef protein. In vitro, HIV-1-infected macrophages or macrophages expressing Nef promoted B cell activation and differentiation to immunoglobulin-secreting cells. Nef-mediated activation of NF-kappaB in macrophages induced secretion of the acute-phase protein ferritin, and ferritin was necessary and sufficient for the observed Nef-dependent B cell changes. The extent of hypergammaglobulinemia in HIV-1-infected individuals correlated directly with plasma ferritin levels and with viral load. Furthermore, the induction of ferritin production and hypergammaglobulinemia was recapitulated when Nef was specifically expressed in macrophages and T cells of transgenic mice. Collectively, these results indicate that the HIV-1 Nef protein carries a pathogenic determinant that governs B cell defects in HIV-1 infection. 相似文献
50.
Haupt S Donhauser N Chaipan C Schuster P Puffer B Daniels RS Greenough TC Kirchhoff F Schmidt B 《Journal of virology》2008,82(17):8900-8905
Plasmacytoid dendritic cells (PDC) are major producers of type I interferons (IFN) in response to human immunodeficiency virus type 1 (HIV-1) infection. To better define the underlying mechanisms, we studied the magnitude of alpha IFN (IFN-α) induction by recombinant viruses containing changes in the Env protein that impair or disrupt CD4 binding or expressing primary env alleles with differential coreceptor tropism. We found that the CD4 binding affinity but not the viral coreceptor usage is critical for the attachment of autofluorescing HIV-1 to PDC and for subsequent IFN-α induction. Our results illustrate the importance of the gp120-CD4 interaction in determining HIV-1-induced immune stimulation via IFN-α production. 相似文献