scholarly journals Mathematical Model of Mechanical Virion-Cell Interaction During Early Engulfment in HIV

2019 ◽  
Author(s):  
Elizabeth Kruse ◽  
Tamer Abdalrahman ◽  
Philippe Selhorst ◽  
Thomas Franz
Keyword(s):  
Mathematical Model ◽  
Cell Membrane ◽  
Early Stage ◽  
Cell Interaction ◽  
Host Cells ◽  
Receptor Complex ◽  
Analytical Functions ◽  
Hiv Entry ◽  
Membrane Contact ◽  
Complex Density

AbstractWhile HIV entry into host cells has been extensively studied from a biological and biochemical perspective, the influence of mechanical parameters of virions and cells on engulfment and invagination is not well understood. The present work aimed at developing a mathematical model to quantify effects of mechanical and morphological parameters on engulfment forces and energies of HIV particles. Invagination force and engulfment energy were described as analytical functions of radius and elastic modulus of virion and cell, ligand-receptor energy density, receptor complex density, and engulfment depth for early stage engulfment. The models were employed to study the effects of (a) virion-membrane contact geometry on required invagination force for global cell geometries and ultrastructural cell membrane features, and (b) virion radius and number of gp120 proteins on engulfment energy. The invagination force was equal for cells of various sizes (i.e. macrophages and lymphocytes), but lower when considering ultrastructural membrane. The magnitude of the normalised engulfment energy was higher for a mature than for an immature, larger virion with the same number of 72 gp120 spikes, but it decreased for a mature virion with a reduced number of gp120 spikes. The results suggest that for early stage engulfment (1) localised cell membrane features promote invagination and may play a role in entry ability, and (2) shedding of gp120 proteins during maturation reduces engulfment energy which is expected to reduce entry ability.

In situ labelling chemistry of respiratory syncytial viruses by employing the biotinylated host-cell membrane protein for tracking the early stage of virus entry

2014 ◽  
Vol 50 (99) ◽  
pp. 15776-15779 ◽  
Author(s):  
Lin Ling Zheng ◽  
Xiao Xi Yang ◽  
Yue Liu ◽  
Xiao Yan Wan ◽  
Wen Bi Wu ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Membrane Protein ◽  
Quantum Dot ◽  
Early Stage ◽  
Virus Entry ◽  
Host Cells ◽  
Host Cell Membrane ◽  
Respiratory Syncytial Viruses ◽  
Cell Membrane Protein

Anin situstrategy for producing quantum dot-labelled respiratory syncytial viruses by incorporating the biotinylated membrane protein of the host cells into mature virions is reported.

scholarly journals Stress-Inducible Gene Atf3 Dictates a Dichotomous Macrophage Activity in Chemotherapy-Enhanced Lung Colonization

2021 ◽  
Vol 22 (14) ◽  
pp. 7356
Author(s):  
Justin D. Middleton ◽  
Jared Fehlman ◽  
Subhakeertana Sivakumar ◽  
Daniel G. Stover ◽  
Tsonwin Hai
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Early Stage ◽  
Mechanistic Explanation ◽  
Host Cells ◽  
Secondary Site ◽  
Initial Increase ◽  
Cell Retention ◽  
Lung Colonization ◽  
Inducible Gene

Previously, we showed that chemotherapy paradoxically exacerbated cancer cell colonization at the secondary site in a manner dependent on Atf3, a stress-inducible gene, in the non-cancer host cells. Here, we present evidence that this phenotype is established at an early stage of colonization within days of cancer cell arrival. Using mouse breast cancer models, we showed that, in the wild-type (WT) lung, cyclophosphamide (CTX) increased the ability of the lung to retain cancer cells in the vascular bed. Although CTX did not change the WT lung to affect cancer cell extravasation or proliferation, it changed the lung macrophage to be pro-cancer, protecting cancer cells from death. This, combined with the initial increase in cell retention, resulted in higher lung colonization in CTX-treated than control-treated mice. In the Atf3 knockout (KO) lung, CTX also increased the ability of lung to retain cancer cells. However, the CTX-treated KO macrophage was highly cytotoxic to cancer cells, resulting in no increase in lung colonization—despite the initial increase in cell retention. In summary, the status of Atf3 dictates the dichotomous activity of macrophage: pro-cancer for CTX-treated WT macrophage but anti-cancer for the KO counterpart. This dichotomy provides a mechanistic explanation for CTX to exacerbate lung colonization in the WT but not Atf3 KO lung.

Potential role of a series of lysine-/leucine-rich antimicrobial peptide in inhibiting lipopolysaccharide-induced inflammation

2018 ◽  
Vol 475 (22) ◽  
pp. 3687-3706 ◽  
Author(s):  
Weibing Dong ◽  
Xin Zhu ◽  
Xuan Zhou ◽  
Ying Yang ◽  
Xin Yan ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Signaling Pathway ◽  
Inflammatory Responses ◽  
Antimicrobial Activities ◽  
Host Cells ◽  
Inflammatory Factors ◽  
Human Macrophage ◽  
U937 Cells ◽  
Wide Range ◽  
Anti Inflammatory

Antimicrobial peptides have broad-spectrum killing activities against bacteria, enveloped viruses, fungi and several parasites via cell membrane permeation and exhibit primarily immunomodulatory and anti-infective functions in their interactions with host cells. However, the mechanism underlying their anti-inflammatory activity remains to be elucidated. L-K6, an analog of temporin-1CEb isolated from the skin secretion of Rana chensinensis, has demonstrated a wide range of antimicrobial activities against gram-negative and gram-positive bacteria. In this study, the potent anti-inflammatory mechanism of L-K6 and its analogs in lipopolysaccharide (LPS)-stimulated human macrophage U937 cells were evaluated. We found that L-K6 suppressed the expression of inflammatory factors by two downstream signaling components in the MyD88-dependent pathway, including the mitogen-activated protein kinases (MAPKs) and the NF (nuclear factor)-κB signaling pathway, but its analog L-K5, which had the same amino acid sequence as L-K6 but no Lys residue at the –COOH terminal, only inhibited the phosphorylation of I-κB and NF-κB. Importantly, L-K6 and L-K5 were actively taken up by U937 cells through an independent cell membrane disruption mechanism and were eventually localized to the perinuclear region. The L-K6 uptake process was mediated by endocytosis, but L-K5 was specifically taken up by U937 cells via TLR4 endocytosis. Our results demonstrated that L-K6 can neutralize LPS and diassociate LPS micelles to inhibit LPS from triggering the proinflammatory signaling pathway, and by partially inhibiting inflammatory responses by the intracellular target. However, L-K5 may mainly inhibit proinflammatory responses by intracellular reporters to modulate the NF-κB signaling pathway.

scholarly journals A simulation to identify the optimal area to survey in the early stage of invasion by Solenopsis invicta

2021 ◽  
Author(s):  
Shumpei Hisamoto ◽  
Koichi Goka ◽  
Yoshiko Sakamoto
Keyword(s):  
Mathematical Model ◽  
Cost Effectiveness ◽  
Solenopsis Invicta ◽  
Early Stage ◽  
Geographical Information ◽  
Survey Area ◽  
Single Colony ◽  
The Status ◽  
Optimal Area ◽  
The Cost

Abstract Efforts to eradicate invasive alien species commonly use simulations to calculate the cost-effectiveness of surveys. Although eradication of Solenopsis invicta in the early stages of an invasion is important, few simulations are available to calculate the cost-effectiveness of surveys when a single colony has been detected. In the case of S. invicta, it is difficult to determine from the status of the detected colony whether new queens have dispersed, so it is necessary to consider dispersal as a probabilistic event and calculate its probability. We therefore first constructed a mathematical model in which we used Bayesian statistics to estimate the probability of dispersal as a function of the results of the survey. This mathematical model revealed that the efficacy of the survey and the associated cost differed greatly between cases depending on whether dispersal was or was not confirmed. Next, we developed a simulation that incorporated this mathematical model to inform the determination of the survey area when a single colony had been detected. The simulation showed how ecological parameters and geographical information could be used to identify an efficacious survey area, even in heterogeneous landscapes such as international ports where invasions occur sporadically. Finally, we used this simulation to assess the efficacy of a survey in the case of an S. invicta outbreak at the Port of Tokyo, Japan. The results suggested that the survey covered a sufficiently wide area but that it could have been designed in a more efficacious manner.

scholarly journals Defining the early stages of intestinal colonisation by whipworms

2020 ◽  
Author(s):  
María A. Duque-Correa ◽  
David Goulding ◽  
Claire Cormie ◽  
Catherine Sharpe ◽  
Judit Gali Moya ◽  
...  
Keyword(s):  
Intestinal Epithelium ◽  
Early Stage ◽  
Proximal Colon ◽  
Host Cells ◽  
Parasitic Nematodes ◽  
Metazoan Parasites ◽  
Multiple Cells ◽  
First Time

ABSTRACTHundreds of millions of people are infected with whipworms (Trichuris trichiura), large metazoan parasites that live in the caecum and proximal colon. Whipworms inhabit distinct multi-intracellular epithelial burrows that have been described as syncytial tunnels. However, the interactions between first-stage (L1) larvae and the host epithelia that determine parasite invasion and establishment in the syncytium remain unclear. In vivo experiments investigating these events have been severely hampered by the limited in situ accessibility to intracellular infective larvae at the bottom of the crypts of Lieberkühn, and the lack of genetic tools such as fluorescent organisms that are readily available for other pathogens but not parasitic nematodes. Moreover, cell lines, which do not mimic the complexity of the intestinal epithelium, have been unsuccessful in supporting infection by whipworm larvae. Here, we show that caecaloids grown in an open crypt-like conformation recapitulate the caecal epithelium. Using this system, we establish in vitro infections with T. muris L1 larvae for the first-time, and provide clear evidence that syncytial tunnels are formed at this early stage. We show that larval whipworms are completely intracellular but woven through multiple cells. Using the caecaloids, we are able to visualise the pathways taken by the larvae as they burrow through the epithelial cells. We also demonstrate that larvae degrade the mucus layers overlaying the epithelium, enabling them to access the cells below. We show that early syncytial tunnels are composed of enterocytes and goblet cells that are alive and actively interacting with the larvae during the first 24 h of the infection. Progression of infection results in damage to host cells and by 72 h post-infection, we show that desmosomes of cells from infected epithelium widen and some host cells appear to become liquified. Collectively, our work unravels processes mediating the intestinal epithelium invasion by whipworms and reveals new specific interactions between the host and the parasite that allow the whipworm to establish on its multi-intracellular niche. Our study demonstrates that caecaloids can be used as a relevant in vitro model to investigate the infection biology of T. muris during the early colonisation of its host.

Metainflammation in COVID-19

2022 ◽  
Vol 22 ◽  
Author(s):  
Mojtaba Bakhtiari ◽  
Kamyar Asadipooya
Keyword(s):  
Cell Membrane ◽  
Viral Entry ◽  
Virus Entry ◽  
Host Cells ◽  
Elderly Men ◽  
Virus Binding ◽  
Angiotensin Converting Enzyme 2 ◽  
Dipeptidyl Peptidase 4 ◽  
Beneficial Effects ◽  
Binding Capability

Abstract: A new coronavirus pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2], has been on the rise. This virus is fatal for broad groups of populations, including elderly, men, and patients with comorbidities among which obesity is a possible risk factor. The pathophysiologic connections between obesity/metainflammation and COVID-19 may be directly related to increasing soluble ACE2 (angiotensin-converting enzyme 2] levels which potentiates the viral entrance into the host cells, or indirectly related to dysregulation of immune system, microvascular injury and hypercoagulability. The SARS-CoV-2 S-glycoprotein interacts mainly with ACE2 or possibly DDP4 receptors to enter into the host cells. The host proteases, especially TMPRSS2 (transmembrane protease serine 2], support the fusion process and virus entry. While membranous ACE2 is considered a port of entry to the cell for SARS-CoV-2, it seems that soluble ACE2 retains its virus binding capability and enhances its entry into the cells. Interestingly, ACE2 on cell membrane may have protective roles by diminishing cytokine storm-related injuries to the organs. Applying medications that can reduce soluble ACE2 levels, antagonizing TMPRSS2 or blocking DDP4 can improve the outcomes of COVID-19. Metformin and statins through immunomodulatory activities, Orlistat by reducing viral replication, and thiazolidinediones by upregulating ACE2 expression have potential beneficial effects against COVID-19. However, the combination of dipeptidyl peptidase-4 (DDP4] inhibitors and spironolactone/eplerenone seems to be more effective by reducing soluble ACE2 level, antagonizing TMPRSS2, maintaining ACE2 on cell membrane and reducing risk of viral entry into the cells.

scholarly journals Reprogramming of Mesothelial-Mesenchymal Transition in Chronic Peritoneal Diseases by Estrogen Receptor Modulation and TGF-β1 Inhibition

2020 ◽  
Vol 21 (11) ◽  
pp. 4158
Author(s):  
Robert B. Wilson ◽  
Rami Archid ◽  
Marc A. Reymond
Keyword(s):  
Estrogen Receptor ◽  
Cell Membrane ◽  
Peritoneal Metastasis ◽  
Tyrosine Kinases ◽  
Membrane Receptors ◽  
Host Cells ◽  
Potential Candidate ◽  
Mesenchymal Transition ◽  
Receptor Modulation ◽  
Tgf Β1

In chronic peritoneal diseases, mesothelial-mesenchymal transition is determined by cues from the extracellular environment rather than just the cellular genome. The transformation of peritoneal mesothelial cells and other host cells into myofibroblasts is mediated by cell membrane receptors, Transforming Growth Factor β1 (TGF-β1), Src and Hypoxia-inducible factor (HIF). This article provides a narrative review of the reprogramming of mesothelial mesenchymal transition in chronic peritoneal diseases, drawing on the similarities in pathophysiology between encapsulating peritoneal sclerosis and peritoneal metastasis, with a particular focus on TGF-β1 signaling and estrogen receptor modulators. Estrogen receptors act at the cell membrane/cytosol as tyrosine kinases that can phosphorylate Src, in a similar way to other receptor tyrosine kinases; or can activate the estrogen response element via nuclear translocation. Tamoxifen can modulate estrogen membrane receptors, and has been shown to be a potent inhibitor of mesothelial-mesenchymal transition (MMT), peritoneal mesothelial cell migration, stromal fibrosis, and neoangiogenesis in the treatment of encapsulating peritoneal sclerosis, with a known side effect and safety profile. The ability of tamoxifen to inhibit the transduction pathways of TGF-β1 and HIF and achieve a quiescent peritoneal stroma makes it a potential candidate for use in cancer treatments. This is relevant to tumors that spread to the peritoneum, particularly those with mesenchymal phenotypes, such as colorectal CMS4 and MSS/EMT gastric cancers, and pancreatic cancer with its desmoplastic stroma. Morphological changes observed during mesothelial mesenchymal transition can be treated with estrogen receptor modulation and TGF-β1 inhibition, which may enable the regression of encapsulating peritoneal sclerosis and peritoneal metastasis.

scholarly journals Minimal model of arterial chaos generated by coupled intracellular and membrane Ca2+oscillators

1999 ◽  
Vol 277 (3) ◽  
pp. H1119-H1144 ◽  
Author(s):  
D. Parthimos ◽  
D. H. Edwards ◽  
T. M. Griffith
Keyword(s):  
Mathematical Model ◽  
Membrane Potential ◽  
Cell Membrane ◽  
Wide Spectrum ◽  
Period Doubling ◽  
Rhythmic Activity ◽  
Vascular Response ◽  
Rabbit Ear ◽  
Dual Action ◽  
Dynamic Variables

We have developed a mathematical model of arterial vasomotion in which irregular rhythmic activity is generated by the nonlinear interaction of intracellular and membrane oscillators that depend on cyclic release of Ca2+ from internal stores and cyclic influx of extracellular Ca2+, respectively. Four key control variables were selected on the basis of the pharmacological characteristics of histamine-induced vasomotion in rabbit ear arteries: Ca2+ concentration in the cytosol, Ca2+ concentration in ryanodine-sensitive stores, cell membrane potential, and the open state probability of Ca2+-activated K+ channels. Although not represented by independent dynamic variables, the model also incorporates Na+/Ca2+exchange, the Na+-K+-ATPase, Cl− fluxes, and Ca2+ efflux via the extrusion ATPase. Simulations reproduce a wide spectrum of experimental observations, including 1) the effects of interventions that modulate the functionality of Ca2+ stores and membrane ion channels, 2) paradoxes such as the apparently unpredictable dual action of Ca2+ antagonists and low extracellular Na+ concentration, which can abolish vasomotion or promote the appearance of large-amplitude oscillations, and 3) period-doubling, quasiperiodic, and intermittent routes to chaos. Nonlinearity is essential to explain these diverse patterns of experimental vascular response.

Voltage-gated K+ channels at an early stage of chronic hypoxia-induced pulmonary hypertension in newborn piglets

2006 ◽  
Vol 291 (6) ◽  
pp. L1169-L1176 ◽  
Author(s):  
Candice D. Fike ◽  
Mark R. Kaplowitz ◽  
Yongmei Zhang ◽  
Jane A. Madden
Keyword(s):  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Cell Membrane ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Chronic Hypoxia ◽  
Early Stage ◽  
Membrane Properties ◽  
Voltage Gated ◽  
Muscle Cell Membrane

Our purpose was to determine whether smooth muscle cell membrane properties are altered in small pulmonary arteries (SPA) of piglets at an early stage of pulmonary hypertension. Piglets were raised in either room air (control) or hypoxia for 3 days. A microelectrode technique was used to measure smooth muscle cell membrane potential ( Em) in cannulated, pressurized SPA (100- to 300-μm diameter). SPA responses to the voltage-gated K+ (KV) channel antagonist 4-aminopyridine (4-AP) and the KV1 family channel antagonist correolide were measured. Other SPA were used to assess amounts of KV1.2, KV1.5, and KV2.1 (immunoblot technique). Em was more positive in SPA of chronically hypoxic piglets than in SPA of comparable-age control piglets. The magnitude of constriction elicited by either 4-AP or correolide was diminished in SPA from hypoxic piglets. Abundances of KV1.2 were reduced, whereas abundances of both KV1.5 and KV2.1 were unaltered, in SPA from hypoxic piglets. At least partly because of reduced amounts of KV1.2, smooth muscle cell membrane properties are altered such that Em is depolarized and KV channel family function is impaired in SPA of piglets at an early stage of chronic hypoxia-induced pulmonary hypertension.

Sign in / Sign up

Export Citation Format

Share Document