scholarly journals Different Patterns of HIV-1 Replication in MACROPHAGES is Led by Co-Receptor Usage

Medicina ◽  
2019 ◽  
Vol 55 (6) ◽  
pp. 297 ◽  
Author(s):  
Borrajo ◽  
Ranazzi ◽  
Pollicita ◽  
Bellocchi ◽  
Salpini ◽  
...  
Keyword(s):  
Cell Death ◽  
Chemokine Receptor ◽  
Post Infection ◽  
Fold Increase ◽  
Initial Increase ◽  
Limited Information ◽  
Induce Cell Death ◽  
Receptor Usage ◽  
The Impact ◽  
Hiv 1

Background and objectives: To enter the target cell, HIV-1 binds not only CD4 but also a co-receptor β-chemokine receptor 5 (CCR5) or α chemokine receptor 4 (CXCR4). Limited information is available on the impact of co-receptor usage on HIV-1 replication in monocyte-derived macrophages (MDM) and on the homeostasis of this important cellular reservoir. Materials and Methods: Replication (measured by p24 production) of the CCR5-tropic 81A strain increased up to 10 days post-infection and then reached a plateau. Conversely, the replication of the CXCR4-tropic NL4.3 strain (after an initial increase up to day 7) underwent a drastic decrease becoming almost undetectable after 10 days post-infection. The ability of CCR5-tropic and CXCR4-tropic strains to induce cell death in MDM was then evaluated. While for CCR5-tropic 81A the rate of apoptosis in MDM was comparable to uninfected MDM, the infection of CXCR4-tropic NL4.3 in MDM was associated with a rate of 14.3% of apoptotic cells at day 6 reaching a peak of 43.5% at day 10 post-infection. Results: This suggests that the decrease in CXCR4-tropic strain replication in MDM can be due to their ability to induce cell death in MDM. The increase in apoptosis was paralleled with a 2-fold increase in the phosphorylated form of p38 compared to WT. Furthermore, microarray analysis showed modulation of proapoptotic and cancer-related genes induced by CXCR4-tropic strains starting from 24 h after infection, whereas CCR5 viruses modulated the expression of genes not correlated with apoptotic-pathways. Conclusions: In conclusion, CXCR4-tropic strains can induce a remarkable depletion of MDM. Conversely, MDM can represent an important cellular reservoir for CCR5-tropic strains supporting the role of CCR5-usage in HIV-1 pathogenesis and as a pharmacological target to contribute to an HIV-1 cure.

scholarly journals Complexity and Dynamics of HIV-1 Chemokine Receptor Usage in a Multidrug-Resistant Adolescent

2014 ◽  
Vol 30 (12) ◽  
pp. 1243-1250 ◽  
Author(s):  
Mariangela Cavarelli ◽  
Lara Mainetti ◽  
Angela Rosa Pignataro ◽  
Alba Bigoloni ◽  
Monica Tolazzi ◽  
...  
Keyword(s):  
Chemokine Receptor ◽  
Multidrug Resistant ◽  
Receptor Usage ◽  
Hiv 1

Abstract 1330: Divergent Control of the Mitochondrial Death Gene BNIP3 by Opposing Actions of the Cellular Factors Nuclear Factor kappaB and E2F-1 in Ventricular Myocytes.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
James Shaw ◽  
Natalia Yurkova ◽  
Kelly Regula ◽  
Tong Zhang ◽  
Floribeth Aguilar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Dna Binding ◽  
Gene Transcription ◽  
Ventricular Myocytes ◽  
Fold Increase ◽  
Genetic Ablation ◽  
The Impact ◽  
Chip Analysis ◽  
In Cells

The hypoxia-inducible death factor Bnip3 is known to provoke mitochondrial perturbations and cell death of ventricular myocytes. The transcriptional control processes that govern Bnip3 gene expression under basal and inducible conditions remain cryptic. Sequence analysis of the Bnip3 promoter revealed the presence of distinct but overlapping DNA binding elements for the cell cycle factor E2F-1 and cellular factor NF-κB. Previously, we reported a survival role for NF-κB in ventricular myocytes. As a step toward elucidating the regulation of Bnip3 gene expression in ventricular myocytes, we tested the impact of E2F-1 and NF-κB on basal and inducible expression of Bnip3. A 2.0 fold increase in Bnip3 gene transcription was observed in cells expression wild type E2F-1 but not in cells expressing an E2F-1 mutant defective for DNA binding. Interestingly, basal Bnip3 gene transcription was increased by 2.5 fold in myocytes rendered defective for NF-κB activation with a non-phosphorylatable form of IκBα. Importantly, genetic ablation of E2F-1 inhibited basal and inducible Bnip3 transcription in NF-κB defective cells. Expression of the p65 subunit of NF-κB in NF-κB defective cells inhibited E2F-1 mediated Bnip3 transcription. Western blot analysis of cardiac cell lysate revealed that p65 NF-κB immunoprecipitated with E2F-1. ChIP analysis of the Bnip3 promoter indicated that the p65 NF-κB bound DNA under normoxic conditions. During hypoxia E2F-1 activity increased where as p65 NF-κB protein levels were decreased. ChIP analysis revealed increased binding of E2F-1 to the Bnip3 promoter during hypoxia which coincided with a 3.5 fold increase in Bnip3 gene transcription. IKKβ mediated activation of NF-κB activation abrogated hypoxia-induced E2F-1 binding to the Bnip3 promoter and Bnip3 gene transcription. To our knowledge our data provide the first direct evidence that a novel relationship exists between p65 NF-κB and E2F-1 for basal and hypoxia-inducible regulation of the Bnip3 promoter. Furthermore, our data highlight a novel survival pathway by which NF-κB averts hypoxia - induced cell death by antagonizing the E2F-1 dependent transcription of Bnip3 in ventricular myocytes.

scholarly journals Targeting the PI3K/Akt Cell Survival Pathway to Induce Cell Death of HIV-1 Infected Macrophages with Alkylphospholipid Compounds

PLoS ONE ◽  
2010 ◽  
Vol 5 (9) ◽  
pp. e13121 ◽  
Author(s):  
Amanda Lucas ◽  
Yuri Kim ◽  
Omayra Rivera-Pabon ◽  
Sunju Chae ◽  
Dong-Hyun Kim ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Survival ◽  
Induce Cell Death ◽  
Survival Pathway ◽  
Hiv 1

scholarly journals A Link Between Methylglyoxal and Heart Failure During HIV-1 Infection

2021 ◽  
Vol 8 ◽  
Author(s):  
Prasanta K. Dash ◽  
Fadhel A. Alomar ◽  
Jesse L. Cox ◽  
JoEllyn McMillan ◽  
Bryan T. Hackfort ◽  
...  
Keyword(s):  
Heart Failure ◽  
Hiv Infection ◽  
Post Infection ◽  
Fold Increase ◽  
Causal Link ◽  
Cardiac Tissues ◽  
Viral Loads ◽  
Microvascular Leakage ◽  
Biochemical Analyses ◽  
Hiv 1

Early-onset heart failure (HF) continues to be a major cause of morbidity and mortality in people living with human immunodeficiency virus type one (HIV-1) infection (PLWH), yet the molecular causes for this remain poorly understood. Herein NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ humanized mice (Hu-mice), plasma from PLWH, and autopsied cardiac tissues from deceased HIV seropositive individuals were used to assess if there is a link between the glycolysis byproduct methylglyoxal (MG) and HF in the setting of HIV-1 infection. At five weeks post HIV infection, Hu-mice developed grade III-IV diastolic dysfunction (DD) with an associated two-fold increase in plasma MG. At sixteen-seventeen weeks post infection, cardiac ejection fraction and fractional shortening also declined by 26 and 35%, and plasma MG increased to four-fold higher than uninfected controls. Histopathological and biochemical analyses of cardiac tissues from Hu-mice 17 weeks post-infection affirmed MG increase with a concomitant decrease in expression of the MG-degrading enzyme glyoxalase-1 (Glo1). The endothelial cell marker CD31 was found to be lower, and coronary microvascular leakage and myocardial fibrosis were prominent. Increasing expression of Glo1 in Hu-mice five weeks post-infection using a single dose of an engineered AAV2/9 (1.7 × 1012 virion particles/kg), attenuated the increases in plasma and cardiac MG levels. Increasing Glo1 also blunted microvascular leakage, fibrosis, and HF seen at sixteen weeks post-infection, without changes in plasma viral loads. In plasma from virally suppressed PLWH, MG was also 3.7-fold higher. In autopsied cardiac tissues from seropositive, HIV individuals with low viral log, MG was 4.2-fold higher and Glo1 was 50% lower compared to uninfected controls. These data show for the first time a causal link between accumulation of MG and HF in the setting of HIV infection.

scholarly journals Inhibition of the lncRNA SAF drives activation of apoptotic effector caspases in HIV-1–infected human macrophages

2019 ◽  
Vol 116 (15) ◽  
pp. 7431-7438 ◽  
Author(s):  
Saikat Boliar ◽  
David W. Gludish ◽  
Kondwani C. Jambo ◽  
Raphael Kamng’ona ◽  
Leonard Mvaya ◽  
...  
Keyword(s):  
Cell Death ◽  
Caspase 3 ◽  
Human Monocyte ◽  
Activity Levels ◽  
Sirna Treatment ◽  
Effector Caspases ◽  
Regulatory Functions ◽  
The Impact ◽  
Hiv 1

Long noncoding RNAs (lncRNAs) impart significant regulatory functions in a diverse array of biological pathways and manipulation of these RNAs provides an important avenue to modulate such pathways, particularly in disease. Our knowledge about lncRNAs’ role in determination of cellular fate during HIV-1 infection remains sparse. Here, we have identified the impact of the lncRNA SAF in regulating apoptotic effector caspases in macrophages, a long-lived cellular reservoir of HIV-1, that are largely immune to virus-induced cell death. Expression of SAF is significantly up-regulated in HIV-1–infected human monocyte-derived macrophages (MDM) compared with bystander and virus-nonexposed cells. A similar enhancement in SAF RNA expression is also detected in the HIV-1–infected airway macrophages obtained by bronchoalveolar lavage of HIV-1–infected individuals. Down-regulation of SAF with siRNA treatment increases caspase-3/7 activity levels in virus-infected MDMs. This induction of apoptotic caspases occurs exclusively in HIV-1–infected macrophages and not in bystander cells, leading to a significant reduction in HIV-1 replication and overall viral burden in the macrophage culture. This study identifies targeting of the lncRNA SAF as a potential means to specifically induce cell death in HIV-1–infected macrophages.

scholarly journals Interleukin-27 promotes autophagy in human serum-induced primary macrophages via an mTOR- and LC3-independent pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sylvain Laverdure ◽  
Ziqiu Wang ◽  
Jun Yang ◽  
Takuya Yamamoto ◽  
Tima Thomas ◽  
...  
Keyword(s):  
Mammalian Target Of Rapamycin ◽  
Fold Increase ◽  
Dependent Manner ◽  
Interleukin 27 ◽  
Autophagy Induction ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
The Impact ◽  
First Time ◽  
Hiv 1

AbstractInterleukin-27 (IL-27) is a cytokine that suppresses human immunodeficiency virus (HIV)-1 infection in macrophages and is considered as an immunotherapeutic reagent for infectious diseases. It is reported that IL-27 suppresses autophagy in Mycobacterium tuberculosis-infected macrophages; however, a role for IL-27 on autophagy induction has been less studied. In this study, we investigated the impact of IL-27 in both autophagy induction and HIV-1 infection in macrophages. Primary human monocytes were differentiated into macrophages using human AB serum (huAB) alone, macrophage-colony stimulating factor (M-CSF) alone, or a combination of IL-27 with huAB or M-CSF. Electron microscopy and immunofluorescence staining demonstrated that a 20-fold increase in autophagosome formation was only detected in IL-27 + huAB-induced macrophages. Western blot analysis indicated that the autophagosome induction was not linked to either dephosphorylation of the mammalian target of rapamycin (mTOR) or lipidation of microtubule-associated protein 1A/1B-light chain 3 (LC3), an autophagosomal marker, implying that IL-27 can induce autophagy through a novel non-canonical pathway. Here we show for the first time that IL-27 induces autophagy during monocyte-to-macrophage differentiation in a subtype-dependent manner.

Fluorous photosensitizers enhance photodynamic therapy with perfluorocarbon nanoemulsions

2017 ◽  
Author(s):  
Ellen Sletten ◽  
Rachael A. Day ◽  
Daniel A. Estabrook ◽  
Jessica K. Logan
Keyword(s):  
Cell Death ◽  
Photodynamic Therapy ◽  
Induce Cell Death ◽  
Perfluorocarbon Nanoemulsions

<p>Photodynamic therapy (PDT) requires photosensitizer, light, and oxygen to induce cell death. The majority of efforts to advance PDT focus only on the first two components. Here, we employ perfluorocarbon nanoemulsions to simultaneously deliver oxygen and photosensitizer. We find that the implementation of fluorous soluble photosensitizers enhances the efficacy of PDT. </p>

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