New permeability pathways induced by the malarial parasite in the membrane of its host erythrocyte: Potential routes for targeting of drugs into infected cells

1987 ◽  
Vol 7 (6) ◽  
pp. 455-463 ◽  
Author(s):  
Hagai Ginsburg ◽  
Wilfred D. Stein
Keyword(s):  
Cell Membrane ◽  
Host Cell ◽  
Malarial Parasite ◽  
Structural Defects ◽  
Transport Systems ◽  
Host Cell Membrane ◽  
Transport Pathways ◽  
Infected Cells ◽  
New Permeability Pathways

Malarial parasites propagate asexually inside the erythrocytes of their vertebrate host. Six hours after invasion, the permeability of the host cell membrane to anions and small nonelectrolytes starts to increase and reaches its peak as the parasite matures. This increased permeability differs from the native transport systems of the normal erythrocyte in its solute selectivity pattern, its enthalpy of activation and its susceptibility to inhibitors, suggesting the appearance of new transport pathways. A biophysical analysis of the permeability data indicates that the selectivity barrier discriminates between permeants according to their hydrogen bonding capacity and has solubilization properties compared to those of iso-butanol. The new permeability pathways could result from structural defects caused in the host cell membrane by the insertion of parasite-derived polypeptides. It is suggested that the unique transport properties of the new pathways be used to target drugs into infected cells, to affect the parasite either directly or through the modulation of the intraerythrocytic environment. The feasibility of drug targeting is demonstrated in in vitro cultures of the human malarial parasite Plasmodium falciparum.

scholarly journals Intracellular host cell membrane remodelling induced by SARS‐CoV‐2 infection in vitro

2021 ◽  
Author(s):  
Lucio Ayres Caldas ◽  
Fabiana Avila Carneiro ◽  
Fabio Luis Monteiro ◽  
Ingrid Augusto ◽  
Luiza Mendonça Higa ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Host Cell ◽  
Host Cell Membrane

scholarly journals Mechanisms of phosphatidylserine influence on viral production: a computational model of Ebola virus matrix protein assembly

2021 ◽  
Author(s):  
Xiao Liu ◽  
Ethan J Pappas ◽  
Monica L Husby ◽  
Robert V Stahelin ◽  
Elsje Pienaar
Keyword(s):  
Cell Membrane ◽  
Computational Model ◽  
Host Cell ◽  
Matrix Protein ◽  
Ebola Virus ◽  
Global Public Health ◽  
Matrix Assembly ◽  
Host Cell Membrane ◽  
Western Africa

Ebola virus (EBOV) infections continue to pose a global public health threat, with high mortality rates and sporadic outbreaks in Central and Western Africa. A quantitative understanding of the key processes driving EBOV assembly and budding could provide valuable insights to inform drug development. Here we used a computational model to evaluate EBOV matrix assembly. Our model focused on the assembly kinetics of VP40, the matrix protein in EBOV, and its interaction with phosphatidylserine (PS) in the host cell membrane. Human cells transfected with VP40-expressing plasmids are capable of producing virus-like particles (VLPs) that closely resemble EBOV virions. We used data from this in vitro VP40 system to calibrate our computational model. PS levels in the host cell membrane had been shown to affect VP40 dynamics as well as VLP production through recruiting VP40 dimers to plasma membrane inner leaflet. Our computational results indicated that PS may have direct influence on VP40 filament growth and affect multiple steps in the assembly and budding of VP40 VLPs. We also proposed that the assembly of VP40 filaments may follow the nucleation-elongation theory where initialization and oligomerization of VP40 are two separate and distinct steps in the assembly process. This work illustrated how computational and experimental approaches can be combined to allow for additional analysis and hypothesis generation. Our findings advanced understanding of the molecular process of EBOV assembly and budding processes and may help the development of new EBOV treatments targeting VP40 matrix assembly.

scholarly journals Statin Drug Therapy May Increase COVID-19 Infection

2020 ◽  
Vol 3 (1) ◽  
pp. 326-327 ◽  
Author(s):  
Sanjaya Kumar Shrestha
Keyword(s):  
Cell Membrane ◽  
Host Cell ◽  
Mevalonate Pathway ◽  
No Production ◽  
Host Cell Membrane ◽  
Enveloped Viruses ◽  
Receptor Mediated Endocytosis ◽  
Key Enzyme ◽  
Statin Drug

Enveloped viruses like Coronavirus acquire their envelope from the host cell membrane which is a bilayer of phospholipid interspersed with cholesterol molecules and proteins. Viruses enter their host cell by coming in contact with their specific receptors. Experiments have shown that when cell membranes are depleted of cholesterol in vitro by Methyl beta cyclodextrin (MβCD) these Coronaviruses are not able to enter the host cell membrane by the process of receptor mediated endocytosis. Statin inhibits HMG Co-A reductase, a key enzyme in the Mevalonate pathway resulting into either very low or no production of endogenous cholesterol by the human cells. This results into upregulation of LDL-R in the cell membrane which may lead to more cholesterol getting incorporated into the cell membrane through LDL-C from the plasma creating greater number of lipid rafts suitable for entry of enveloped viruses by receptor-mediated endocytosis.

Association of matrix protein of respiratory syncytial virus with the host cell membrane of infected cells

2003 ◽  
Vol 149 (1) ◽  
pp. 199-210 ◽  
Author(s):  
A. Marty ◽  
J. Meanger ◽  
J. Mills ◽  
B. Shields ◽  
R. Ghildyal
Keyword(s):  
Respiratory Syncytial Virus ◽  
Cell Membrane ◽  
Host Cell ◽  
Matrix Protein ◽  
Host Cell Membrane ◽  
Infected Cells ◽  
Syncytial Virus

Shigella-induced necrosis and apoptosis of U937 cells and J774 macrophages

Microbiology ◽  
2003 ◽  
Vol 149 (9) ◽  
pp. 2513-2527 ◽  
Author(s):  
Takashi Nonaka ◽  
Taku Kuwabara ◽  
Hitomi Mimuro ◽  
Asaomi Kuwae ◽  
Shinobu Imajoh-Ohmi
Keyword(s):  
Cell Death ◽  
Cell Membrane ◽  
Host Cell ◽  
Caspase 3 ◽  
Cytochalasin D ◽  
Host Cells ◽  
U937 Cells ◽  
Host Cell Membrane ◽  
Caspase 1 ◽  
Infected Cells

It is currently unclear whether Shigella kills its phagocytic host cells by apoptosis or necrosis. This study shows that rapid necrosis ensues in macrophage-like cell lines (U937 cells differentiated by all-trans-retinoic acid and J774 cells) infected with the Shigella flexneri strain YSH6000. The infected cells rapidly lose membrane integrity, a typical feature of necrosis, as indicated by the release of the cytoplasmic lactate dehydrogenase and the exposure of phosphatidylserine (PS) associated with the rapid uptake of propidium iodide (PI). The infected cells exhibit DNA fragmentation without nuclear condensation, and substantial involvement of either caspase-3/-7 or caspase-1 was not detected, which is also contrary to what is normally observed in apoptosis. Cytochalasin D potently inhibited Shigella-induced cell death, indicating that only internalized Shigella can cause necrosis. Osmoprotectants such as polyethylene glycols could suppress cell death, suggesting that insertion of a pore by Shigella into the host cell membrane induces the necrosis. The pore was estimated to be 2·87±0·4 nm in diameter. Shigella was also found to be able to induce apoptosis but only in one of the lines tested and under specific conditions, namely U937 cells differentiated with interferon-γ (U937IFN). Caspase-3/-7 but not caspase-1 activation was observed in these infected cells and the exposure of PS occurred without the uptake of PI. An avirulent Shigella strain, wild-type Shigella killed with gentamicin, and even Escherichia coli strain JM109, could also induce apoptosis in U937IFN cells, and cytochalasin D could not prevent apoptosis. It appears therefore that Shigella-induced apoptosis of U937IFN cells is unrelated to Shigella pathogenicity and does not require bacterial internalization. Thus, Shigella can induce rapid necrosis of macrophage-like cells in a virulence-related manner by forming pores in the host cell membrane while some cells can be killed through apoptosis in a virulence-independent fashion.

scholarly journals Revisiting Ehrlichia ruminantium Replication Cycle Using Proteomics: The Host and the Bacterium Perspectives

2021 ◽  
Vol 9 (6) ◽  
pp. 1144
Author(s):  
Isabel Marcelino ◽  
Philippe Holzmuller ◽  
Ana Coelho ◽  
Gabriel Mazzucchelli ◽  
Bernard Fernandez ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Host Cell ◽  
Cell Metabolism ◽  
Replication Cycle ◽  
Host Cells ◽  
Ehrlichia Ruminantium ◽  
Host Interaction ◽  
Infected Cells ◽  
Related Proteins

The Rickettsiales Ehrlichia ruminantium, the causal agent of the fatal tick-borne disease Heartwater, induces severe damage to the vascular endothelium in ruminants. Nevertheless, E. ruminantium-induced pathobiology remains largely unknown. Our work paves the way for understanding this phenomenon by using quantitative proteomic analyses (2D-DIGE-MS/MS, 1DE-nanoLC-MS/MS and biotin-nanoUPLC-MS/MS) of host bovine aorta endothelial cells (BAE) during the in vitro bacterium intracellular replication cycle. We detect 265 bacterial proteins (including virulence factors), at all time-points of the E. ruminantium replication cycle, highlighting a dynamic bacterium–host interaction. We show that E. ruminantium infection modulates the expression of 433 host proteins: 98 being over-expressed, 161 under-expressed, 140 detected only in infected BAE cells and 34 exclusively detected in non-infected cells. Cystoscape integrated data analysis shows that these proteins lead to major changes in host cell immune responses, host cell metabolism and vesicle trafficking, with a clear involvement of inflammation-related proteins in this process. Our findings led to the first model of E. ruminantium infection in host cells in vitro, and we highlight potential biomarkers of E. ruminantium infection in endothelial cells (such as ROCK1, TMEM16K, Albumin and PTPN1), which may be important to further combat Heartwater, namely by developing non-antibiotic-based strategies.

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