scholarly journals HIV Type 1 Infection Up-Regulates TLR2 and TLR4 Expression and Function in Vivo and in Vitro

2012 ◽  
Vol 28 (10) ◽  
pp. 1313-1328 ◽  
Author(s):  
Juan C. Hernández ◽  
Mario Stevenson ◽  
Eicke Latz ◽  
Silvio Urcuqui-Inchima
Keyword(s):  
Tlr4 Expression ◽  
Hiv Type 1 ◽  
And Function

scholarly journals Bacterial Outer Membrane Ushers Contain Distinct Targeting and Assembly Domains for Pilus Biogenesis

2002 ◽  
Vol 184 (22) ◽  
pp. 6260-6269 ◽  
Author(s):  
David G. Thanassi ◽  
Christos Stathopoulos ◽  
Karen Dodson ◽  
Dominik Geiger ◽  
Scott J. Hultgren
Keyword(s):  
Outer Membrane ◽  
Secretory Pathway ◽  
Terminal Branch ◽  
C Terminus ◽  
Type 1 Pili ◽  
Pilus Biogenesis ◽  
And Function

ABSTRACT Biogenesis of a superfamily of surface structures by gram-negative bacteria requires the chaperone/usher pathway, a terminal branch of the general secretory pathway. In this pathway a periplasmic chaperone works together with an outer membrane usher to direct substrate folding, assembly, and secretion to the cell surface. We analyzed the structure and function of the PapC usher required for P pilus biogenesis by uropathogenic Escherichia coli. Structural analysis indicated PapC folds as a β-barrel with short extracellular loops and extensive periplasmic domains. Several periplasmic regions were localized, including two domains containing conserved cysteine pairs. Functional analysis of deletion mutants revealed that the PapC C terminus was not required for insertion of the usher into the outer membrane or for proper folding. The usher C terminus was not necessary for interaction with chaperone-subunit complexes in vitro but was required for pilus biogenesis in vivo. Interestingly, coexpression of PapC C-terminal truncation mutants with the chromosomal fim gene cluster coding for type 1 pili allowed P pilus biogenesis in vivo. These studies suggest that chaperone-subunit complexes target an N-terminal domain of the usher and that subunit assembly into pili depends on a subsequent function provided by the usher C terminus.

scholarly journals Lentiviral Nef Proteins Utilize PAK2-Mediated Deregulation of Cofilin as a General Strategy To Interfere with Actin Remodeling

2010 ◽  
Vol 84 (8) ◽  
pp. 3935-3948 ◽  
Author(s):  
Bettina Stolp ◽  
Libin Abraham ◽  
Jochen M. Rudolph ◽  
Oliver T. Fackler
Keyword(s):  
Host Cells ◽  
General Strategy ◽  
Actin Remodeling ◽  
Mechanistic Analysis ◽  
Immunodeficiency Virus ◽  
Hiv Type 1 ◽  
Hiv 1

ABSTRACT Nef is an accessory protein and pathogenicity factor of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) which elevates virus replication in vivo. We recently described for HIV type 1SF2 (HIV-1SF2) the potent interference of Nef with T-lymphocyte chemotaxis via its association with the cellular kinase PAK2. Mechanistic analysis revealed that this interaction results in deregulation of the actin-severing factor cofilin and thus blocks the chemokine-mediated actin remodeling required for cell motility. However, the efficiency of PAK2 association is highly variable among Nef proteins from different lentiviruses, prompting us to evaluate the conservation of this actin-remodeling/cofilin-deregulating mechanism. Based on the analysis of a total of 17 HIV-1, HIV-2, and SIV Nef proteins, we report here that inhibition of chemokine-induced actin remodeling as well as inactivation of cofilin are strongly conserved activities of lentiviral Nef proteins. Of note, even for Nef variants that display only marginal PAK2 association in vitro, these activities require the integrity of a PAK2 recruitment motif and the presence of endogenous PAK2. Thus, reduced in vitro affinity to PAK2 does not indicate limited functionality of Nef-PAK2 complexes in intact HIV-1 host cells. These results establish hijacking of PAK2 for deregulation of cofilin and inhibition of triggered actin remodeling as a highly conserved function of lentiviral Nef proteins, supporting the notion that PAK2 association may be critical for Nef's activity in vivo.

scholarly journals In Vitro Antiviral Interaction of Lopinavir with Other Protease Inhibitors

2002 ◽  
Vol 46 (7) ◽  
pp. 2249-2253 ◽  
Author(s):  
Akhteruzzaman Molla ◽  
Hongmei Mo ◽  
Sudthida Vasavanonda ◽  
Lixin Han ◽  
C. Thomas Lin ◽  
...  
Keyword(s):  
Protease Inhibitors ◽  
Drug Combination ◽  
Wild Type ◽  
Synergistic Inhibition ◽  
Drug Concentrations ◽  
Immunodeficiency Virus ◽  
Hiv Type 1

ABSTRACT The in vitro inhibition of wild-type human immunodeficiency virus (HIV) by combinations of lopinavir and six other protease inhibitors over a range of two-drug combination ratios was evaluated. Combinations of lopinavir with indinavir, nelfinavir, amprenavir, tipranavir, and BMS-232632 generally displayed an additive relationship. In contrast, a consistent, statistically significant synergistic inhibition of HIV type 1 replication with combinations of lopinavir and saquinavir was observed. Analysis of the combination indices indicated that lopinavir with saquinavir was synergistic over the entire range of drug combination ratios tested and at all levels of inhibition in excess of 40%. Cellular toxicity was not observed at the highest drug concentrations tested. These results suggest that administration of combinations of the appropriate dose of lopinavir with other protease inhibitors in vivo may result in enhanced antiviral activity with no associated increase in cellular cytotoxicity. More importantly, the observed in vitro synergy between lopinavir and saquinavir provides a theoretical basis for the clinical exploration of a novel regimen of lopinavir-ritonavir and saquinavir.

In Vivo Expansion Coincident with Excessive in Vitro Cell Death within the Memory Subset of CD8+ T Cells in HIV Type 1 Infection

1999 ◽  
Vol 15 (3) ◽  
pp. 265-272 ◽  
Author(s):  
Emiliano N. Mugnaini ◽  
Lise L. Haaheim ◽  
Mette Sannes ◽  
Jan E. Brinchmann
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Cd8 T Cells ◽  
Hiv Type 1 ◽  
Memory Subset

scholarly journals Type-2 pericytes participate in normal and tumoral angiogenesis

2014 ◽  
Vol 307 (1) ◽  
pp. C25-C38 ◽  
Author(s):  
Alexander Birbrair ◽  
Tan Zhang ◽  
Zhong-Min Wang ◽  
Maria Laura Messi ◽  
John D. Olson ◽  
...  
Keyword(s):  
Blood Perfusion ◽  
Tissue Growth ◽  
Cellular Target ◽  
Vascular Insufficiency ◽  
Inhibition Of Angiogenesis ◽  
And Function

Tissue growth and function depend on vascularization, and vascular insufficiency or excess exacerbates many human diseases. Identification of the biological processes involved in angiogenesis will dictate strategies to modulate reduced or excessive vessel formation. We examine the essential role of pericytes. Their heterogeneous morphology, distribution, origins, and physiology have been described. Using double-transgenic Nestin-GFP/NG2-DsRed mice, we identified two pericyte subsets. We found that Nestin-GFP−/NG2-DsRed+ (type-1) and Nestin-GFP+/NG2-DsRed+ (type-2) pericytes attach to the walls of small and large blood vessels in vivo; in vitro, type-2, but not type-1, pericytes spark endothelial cells to form new vessels. Matrigel assay showed that only type-2 pericytes participate in normal angiogenesis. Moreover, when cancer cells were transplanted into Nestin-GFP/NG2-DsRed mice, type-1 pericytes did not penetrate the tumor, while type-2 pericytes were recruited during its angiogenesis. As inhibition of angiogenesis is a promising strategy in cancer therapy, type-2 pericytes may provide a cellular target susceptible to signaling and pharmacological manipulation in treating malignancy. This work also reports the potential of type-2 pericytes to improve blood perfusion in ischemic hindlimbs, indicating their potential for treating ischemic illnesses.

scholarly journals Comparative Analysis of the Influence of Extracellular Matrix Biomimetics on the Viability and Insulin-Producing Function of Isolated Pancreatic Islets

2021 ◽  
Vol 3 (2) ◽  
Keyword(s):  
Pancreatic Islets ◽  
Structure And Function ◽  
Human Pancreas ◽  
Isolated Pancreatic Islets ◽  
Tissue Specific ◽  
And Function ◽  
Morphofunctional Analysis

The creation of a pancreas tissue-engineered construct based on isolated pancreatic islets is hindered by problems associated with maintaining their viability and insulin-producing function. Both biopolymer and tissue-specific scaffolds can contribute to the maintenance of the structure and function of pancreatic islets in vitro and in vivo. A comparative morphofunctional analysis in vitro of isolated pancreatic islets cultured with a biopolymer collagen-containing scaffold and a tissue-specific scaffold obtained as a result of pancreatic decellularization was performed. The results showed that the use of the scaffolds contributes not only to the maintenance of the cultured islets viability, but also to the prolongation of their insulin-producing functions, compared to the islets monoculture in vitro. A significant increase was found in basal and stimulated (under glucose loading) insulin secreted by the islets cultured with the scaffolds. At the same time, the advantage of using a tissue-specific scaffold in comparison with a biopolymer collagen-containing scaffold was shown. We think that these studies will become a platform for creating a human pancreas tissue-engineered design for the treatment of type 1 diabetes.

scholarly journals Transcriptional start site heterogeneity modulates the structure and function of the HIV-1 genome

2016 ◽  
Vol 113 (47) ◽  
pp. 13378-13383 ◽  
Author(s):  
Siarhei Kharytonchyk ◽  
Sarah Monti ◽  
Philip J. Smaldino ◽  
Verna Van ◽  
Nicholas C. Bolden ◽  
...  
Keyword(s):  
Transcription Initiation ◽  
Transcriptional Start Site ◽  
Structure And Function ◽  
Transcription Start ◽  
Transcription Start Sites ◽  
Hiv Type 1 ◽  
And Function ◽  
Hiv 1

The promoter in HIV type 1 (HIV-1) proviral DNA contains three sequential guanosines at the U3–R boundary that have been proposed to function as sites for transcription initiation. Here we show that all three sites are used in cells infected with HIV-1 and that viral RNAs containing a single 5′ capped guanosine (Cap1G) are specifically selected for packaging in virions, consistent with a recent report [Masuda et al. (2015)Sci Rep5:17680]. In addition, we now show that transcripts that begin with two or three capped guanosines (Cap2G orCap3G) are enriched on polysomes, indicating that RNAs synthesized from different transcription start sites have different functions in viral replication. Because genomes are selected for packaging as dimers, we examined the in vitro monomer–dimer equilibrium properties ofCap1G,Cap2G, andCap3G 5′-leader RNAs in the NL4-3 strain of HIV-1. Strikingly, under physiological-like ionic conditions in which theCap1G 5′-leader RNA adopts a dimeric structure, theCap2G andCap3G 5′-leader RNAs exist predominantly as monomers. Mutagenesis studies designed to probe for base-pairing interactions suggest that the additional guanosines of the 2G and 3G RNAs remodel the base of the PolyA hairpin, resulting in enhanced sequestration of dimer-promoting residues and stabilization of the monomer. Our studies suggest a mechanism through which the structure, function, and fate of the viral genome can be modulated by the transcriptionally controlled presence or absence of a single 5′ guanosine.

scholarly journals CD25+ CD4+ T Cells, Expanded with Dendritic Cells Presenting a Single Autoantigenic Peptide, Suppress Autoimmune Diabetes

2004 ◽  
Vol 199 (11) ◽  
pp. 1467-1477 ◽  
Author(s):  
Kristin V. Tarbell ◽  
Sayuri Yamazaki ◽  
Kara Olson ◽  
Priscilla Toy ◽  
Ralph M. Steinman
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd4 T Cells ◽  
Autoimmune Diabetes ◽  
Nod Mice ◽  
Nonobese Diabetic ◽  
And Function

In the nonobese diabetic (NOD) mouse model of type 1 diabetes, the immune system recognizes many autoantigens expressed in pancreatic islet β cells. To silence autoimmunity, we used dendritic cells (DCs) from NOD mice to expand CD25+ CD4+ suppressor T cells from BDC2.5 mice, which are specific for a single islet autoantigen. The expanded T cells were more suppressive in vitro than their freshly isolated counterparts, indicating that DCs from autoimmune mice can increase the number and function of antigen-specific, CD25+ CD4+ regulatory T cells. Importantly, only 5,000 expanded CD25+ CD4+ BDC2.5 T cells could block autoimmunity caused by diabetogenic T cells in NOD mice, whereas 105 polyclonal, CD25+ CD4+ T cells from NOD mice were inactive. When islets were examined in treated mice, insulitis development was blocked at early (3 wk) but not later (11 wk) time points. The expanded CD25+ CD4+ BDC2.5 T cells were effective even if administered 14 d after the diabetogenic T cells. Our data indicate that DCs can generate CD25+ CD4+ T cells that suppress autoimmune disease in vivo. This might be harnessed as a new avenue for immunotherapy, especially because CD25+ CD4+ regulatory cells responsive to a single autoantigen can inhibit diabetes mediated by reactivity to multiple antigens.

Sign in / Sign up

Export Citation Format

Share Document