scholarly journals Potassium Ion Channels of Chlorella Viruses Cause Rapid Depolarization of Host Cells during Infection

2006 ◽  
Vol 80 (5) ◽  
pp. 2437-2444 ◽  
Author(s):  
Florian Frohns ◽  
Anja Käsmann ◽  
Detlef Kramer ◽  
Britta Schäfer ◽  
Mario Mehmel ◽  
...  
Keyword(s):  
Membrane Depolarization ◽  
Host Cells ◽  
Early Event ◽  
Potassium Ion Channels ◽  
Channel Blockers ◽  
Thin Sections ◽  
Host Interactions ◽  
Internal Membrane ◽  
Structural And Functional Properties ◽  
Dna Release

ABSTRACT Previous studies have established that chlorella viruses encode K+ channels with different structural and functional properties. In the current study, we exploit the different sensitivities of these channels to Cs+ to determine if the membrane depolarization observed during virus infection is caused by the activities of these channels. Infection of Chlorella NC64A with four viruses caused rapid membrane depolarization of similar amplitudes, but with different kinetics. Depolarization was fastest after infection with virus SC-1A (half time [t 1/2], about 9 min) and slowest with virus NY-2A (t 1/2, about 12 min). Cs+ inhibited membrane depolarization only in viruses that encode a Cs+-sensitive K+ channel. Collectively, the results indicate that membrane depolarization is an early event in chlorella virus-host interactions and that it is correlated with viral-channel activity. This suggestion was supported by investigations of thin sections of Chlorella cells, which show that channel blockers inhibit virus DNA release into the host cell. Together, the data indicate that the channel is probably packaged in the virion, presumably in its internal membrane. We hypothesize that fusion of the virus internal membrane with the host plasma membrane results in an increase in K+ conductance and membrane depolarization; this depolarization lowers the energy barrier for DNA release into the host.

scholarly journals IKKε isoform switching governs the immune response against EV71 infection

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Ya-Ling Chang ◽  
Yu-Wen Liao ◽  
Min-Hsuan Chen ◽  
Sui-Yuan Chang ◽  
Yao-Ting Huang ◽  
...  
Keyword(s):  
Host Cells ◽  
Ev71 Infection ◽  
Virus Propagation ◽  
Host Interactions ◽  
Reciprocal Interactions ◽  
Isoform Switching ◽  
Gene Regulatory ◽  
Potential Strategy ◽  
Antiviral Innate Immunity ◽  
Interferon Responses

AbstractThe reciprocal interactions between pathogens and hosts are complicated and profound. A comprehensive understanding of these interactions is essential for developing effective therapies against infectious diseases. Interferon responses induced upon virus infection are critical for establishing host antiviral innate immunity. Here, we provide a molecular mechanism wherein isoform switching of the host IKKε gene, an interferon-associated molecule, leads to alterations in IFN production during EV71 infection. We found that IKKε isoform 2 (IKKε v2) is upregulated while IKKε v1 is downregulated in EV71 infection. IKKε v2 interacts with IRF7 and promotes IRF7 activation through phosphorylation and translocation of IRF7 in the presence of ubiquitin, by which the expression of IFNβ and ISGs is elicited and virus propagation is attenuated. We also identified that IKKε v2 is activated via K63-linked ubiquitination. Our results suggest that host cells induce IKKε isoform switching and result in IFN production against EV71 infection. This finding highlights a gene regulatory mechanism in pathogen-host interactions and provides a potential strategy for establishing host first-line defense against pathogens.

scholarly journals Impaired Insulin Secretion by Diphenyleneiodium Associated with Perturbation of Cytosolic Ca2+ Dynamics in Pancreatic β-Cells

Endocrinology ◽  
2008 ◽  
Vol 149 (11) ◽  
pp. 5391-5400 ◽  
Author(s):  
Hirofumi Imoto ◽  
Nobuhiro Sasaki ◽  
Masanori Iwase ◽  
Udai Nakamura ◽  
Miwako Oku ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Nadph Oxidase ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Mitochondrial Respiratory Chain ◽  
Membrane Depolarization ◽  
Oxidase Inhibitor ◽  
Channel Blockers ◽  
Β Cells ◽  
Impaired Insulin Secretion ◽  
Impaired Insulin

Pancreatic islets express the superoxide-producing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system, but its role remains unknown. To address this, we studied the mechanisms of impaired insulin secretion induced by diphenyleneiodium (DPI), an NADPH oxidase inhibitor. We investigated the effects of DPI on glucose- and nonfuel-stimulated insulin secretion, islet glucose metabolism, and intracellular Ca2+ concentration ([Ca2+]i) dynamics in rat islets and β-cell line RINm5F cells. DPI did not affect insulin secretion at 3.3 mm glucose but totally suppressed insulin secretion stimulated by 16.7 mm glucose (percentage of control, 9.2 ± 1.2%; P <0.001). DPI also inhibited insulin release by high K+-induced membrane depolarization (percentage of control, 36.0 ± 5.3%; P <0.01) and protein kinase C activation (percentage of control, 30.2 ± 10.6% in the presence of extracellular Ca2+, P <0.01; percentage of control, 42.0 ± 4.7% in the absence of extracellular Ca2+, P <0.01). However, DPI had no effect on mastoparan-induced insulin secretion at 3.3 and 16.7 mm glucose under Ca2+-free conditions. DPI significantly suppressed islet glucose oxidation and ATP content through its known inhibitory action on complex I in the mitochondrial respiratory chain. On the other hand, DPI altered [Ca2+]i dynamics in response to high glucose and membrane depolarization, and DPI per se dose-dependently increased [Ca2+]i. The DPI-induced [Ca2+]i rise was associated with a transient increase in insulin secretion and was attenuated by removal of extracellular Ca2+, by L-type voltage-dependent Ca2+ channel blockers, by mitochondrial inhibitors, or by addition of 0.1 or 1.0 μm H2O2 exogenously. Our results showed that DPI impairment of insulin secretion involved altered Ca2+ signaling, suggesting that NADPH oxidase may modulate Ca2+ signaling in β-cells.

Abstract P258: The Use Of Ace Inhibitors And Angiotensin Receptor Blockers Is Associated With Decreased Mortality And Increased Hospitalization Rate In Covid-19 Patients

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Aaron Douen ◽  
Jeremy Oh ◽  
Wesley Romney ◽  
Ryan Panetti ◽  
Prakash Ramdass ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Angiotensin Receptor Blockers ◽  
Hospitalization Rate ◽  
Host Cells ◽  
Channel Blockers ◽  
Multivariate Logistic Regression ◽  
Converting Enzyme Inhibitors ◽  
All Cause Mortality ◽  
Receptor Blockers ◽  
Secondary Outcomes

Introduction: Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are well known for upregulating ACE2 receptors. SARS-Cov-2 (COVID-19) infection utilizes the ACE2 receptor for proliferation and infection of host cells. Hypothesis: We hypothesize that the use of ACEI/ARBs will lead to a higher mortality and hospitalization rate among COVID-19 infected patients. Methods: The electronic health database at a public hospital in New York City was queried retrospectively for patients 18 years and older with a positive test for COVID-19 between 3/1/2020 - 4/1/2021. We examined baseline characteristics including comorbidities and whether they were prescribed ACEI/ARBs versus other medications including beta-blockers, calcium channel blockers, thiazides, or hydralazine. We categorized patients based on ACEI/ARB. The primary outcomes were all-cause mortality and hospitalization. The secondary outcomes were acute kidney injury, ventricular arrhythmia, myocardial infarction, heart failure, and intubation. We adjusted for comorbidities using multivariate logistic regression. Results: We identified 23,068 patients positive for SARS-CoV-2; 1,385 on ACEI/ARBs and 21,683 not on ACE/ARBs. The mean age in years was 65.90 +- 14.35 (SEM 0.386) and 44.01+-16.76, (SEM 0.114) for ACEI/ARB and non-ACEI/ARB respectively (p<0.001). The incidence of all cause mortality and hospitalization rate were significantly greater in the ACEI/ARB group. However, when adjusted for comorbidities using multivariate logistic regression, OR for mortality was 0.41 (CI 0.32-0.52, p<0.001) and for hospitalization was 4.12 (CI 3.49-4.86 p<0.001). For the secondary outcomes, non-ACEI/ARB patients had significantly increased unadjusted odds of all outcomes (p<0.001), except for ventricular tachycardia (p<0.618) and intubation (p< 0.214). Conclusion: Patients in the ACEI/ARB group demonstrated significantly lower mortality and increased hospitalization rates. Increased hospitalization may be due to more comorbidities. These results highlight the importance of continuing the use of ACEI and ARBs in COVID-19 patients for treatment of comorbidities and cardioprotective effects.

scholarly journals N-Glycolyl GM1 Ganglioside as a Receptor for Simian Virus 40

2007 ◽  
Vol 81 (23) ◽  
pp. 12846-12858 ◽  
Author(s):  
Maria A. Campanero-Rhodes ◽  
Alicia Smith ◽  
Wengang Chai ◽  
Sandro Sonnino ◽  
Laura Mauri ◽  
...  
Keyword(s):  
Simian Virus 40 ◽  
High Specificity ◽  
Simian Virus ◽  
Receptor Expression ◽  
Host Cells ◽  
Gm1 Ganglioside ◽  
Ganglioside Gm1 ◽  
Virus Binding ◽  
Host Interactions ◽  
Sv40 Infection

ABSTRACT Carbohydrate microarrays have emerged as powerful tools in analyses of microbe-host interactions. Using a microarray with 190 sequence-defined oligosaccharides in the form of natural glycolipids and neoglycolipids representative of diverse mammalian glycans, we examined interactions of simian virus 40 (SV40) with potential carbohydrate receptors. While the results confirmed the high specificity of SV40 for the ganglioside GM1, they also revealed that N-glycolyl GM1 ganglioside [GM1(Gc)], which is characteristic of simian species and many other nonhuman mammals, is a better ligand than the N-acetyl analog [GM1(Ac)] found in mammals, including humans. After supplementing glycolipid-deficient GM95 cells with GM1(Ac) and GM1(Gc) gangliosides and the corresponding neoglycolipids with phosphatidylethanolamine lipid groups, it was found that GM1(Gc) analogs conferred better virus binding and infectivity. Moreover, we visualized the interaction of NeuGc with VP1 protein of SV40 by molecular modeling and identified a conformation for GM1(Gc) ganglioside in complex with the virus VP1 pentamer that is compatible with its presentation as a membrane receptor. Our results open the way not only to detailed studies of SV40 infection in relation to receptor expression in host cells but also to the monitoring of changes that may occur with time in receptor usage by the virus.

scholarly journals MicroRNAs and Mammarenaviruses: Modulating Cellular Metabolism

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2525
Author(s):  
Jorlan Fernandes ◽  
Renan Lyra Miranda ◽  
Elba Regina Sampaio de Lemos ◽  
Alexandro Guterres
Keyword(s):  
Metabolic Pathways ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Mirna Expression Profile ◽  
Metabolic Reprogramming ◽  
Host Cells ◽  
Emerging Viruses ◽  
Cellular Mirnas ◽  
Host Interactions ◽  
Causative Agents

Mammarenaviruses are a diverse genus of emerging viruses that include several causative agents of severe viral hemorrhagic fevers with high mortality in humans. Although these viruses share many similarities, important differences with regard to pathogenicity, type of immune response, and molecular mechanisms during virus infection are different between and within New World and Old World viral infections. Viruses rely exclusively on the host cellular machinery to translate their genome, and therefore to replicate and propagate. miRNAs are the crucial factor in diverse biological processes such as antiviral defense, oncogenesis, and cell development. The viral infection can exert a profound impact on the cellular miRNA expression profile, and numerous RNA viruses have been reported to interact directly with cellular miRNAs and/or to use these miRNAs to augment their replication potential. Our present study indicates that mammarenavirus infection induces metabolic reprogramming of host cells, probably manipulating cellular microRNAs. A number of metabolic pathways, including valine, leucine, and isoleucine biosynthesis, d-Glutamine and d-glutamate metabolism, thiamine metabolism, and pools of several amino acids were impacted by the predicted miRNAs that would no longer regulate these pathways. A deeper understanding of mechanisms by which mammarenaviruses handle these signaling pathways is critical for understanding the virus/host interactions and potential diagnostic and therapeutic targets, through the inhibition of specific pathologic metabolic pathways.

scholarly journals A Virus-Virus Interaction Circumvents the Virus Receptor Requirement for Infection by Pathogenic Retroviruses

2003 ◽  
Vol 77 (6) ◽  
pp. 3460-3469 ◽  
Author(s):  
David L. Wensel ◽  
Weihua Li ◽  
James M. Cunningham
Keyword(s):  
Cell Surface ◽  
Envelope Glycoprotein ◽  
Gene Activation ◽  
Host Cells ◽  
Virus Binding ◽  
Virus Envelope ◽  
Host Interactions ◽  
Terminal Domain ◽  
Retrovirus Infection ◽  
Ecotropic Virus

ABSTRACT During ongoing C-type retrovirus infection, the probability of leukemia caused by insertional gene activation is markedly increased by the emergence of recombinant retroviruses that repeatedly infect host cells. The murine mink cell focus-inducing (MCF) viruses with this property have acquired characteristic changes in the N-terminal domain of their envelope glycoprotein that specify binding to a different receptor than the parental ecotropic virus. In this report, we show that MCF virus infection occurs through binding to this receptor (termed Syg1) and, remarkably, by a second mechanism that does not utilize the Syg1 receptor. By the latter route, the N-terminal domain of the ecotropic virus glycoprotein expressed on the cell surface in a complex with its receptor activates the fusion mechanism of the MCF virus in trans. The rate of MCF virus spread through a population of permissive human cells was increased by establishment of trans activation, indicating that Syg1 receptor-dependent and -independent pathways function in parallel. Also, trans activation shortened the interval between initial infection and onset of cell-cell fusion associated with repeated infection of the same cell. Our findings indicate that pathogenic retrovirus infection may be initiated by virus binding to cell receptors or to the virus envelope glycoprotein of other viruses expressed on the cell surface. Also, they support a broader principle: that cooperative virus-virus interactions, as well as virus-host interactions, shape the composition and properties of the retrovirus quasispecies.

scholarly journals Glycans in Virus-Host Interactions: A Structural Perspective

2021 ◽  
Vol 8 ◽  
Author(s):  
Nathaniel L. Miller ◽  
Thomas Clark ◽  
Rahul Raman ◽  
Ram Sasisekharan
Keyword(s):  
Immune System ◽  
Host Cells ◽  
Host Immune System ◽  
Host Interactions ◽  
Viral Glycoproteins ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Anti Hiv ◽  
Structural Perspective

Many interactions between microbes and their hosts are driven or influenced by glycans, whose heterogeneous and difficult to characterize structures have led to an underappreciation of their role in these interactions compared to protein-based interactions. Glycans decorate microbe glycoproteins to enhance attachment and fusion to host cells, provide stability, and evade the host immune system. Yet, the host immune system may also target these glycans as glycoepitopes. In this review, we provide a structural perspective on the role of glycans in host-microbe interactions, focusing primarily on viral glycoproteins and their interactions with host adaptive immunity. In particular, we discuss a class of topological glycoepitopes and their interactions with topological mAbs, using the anti-HIV mAb 2G12 as the archetypical example. We further offer our view that structure-based glycan targeting strategies are ready for application to viruses beyond HIV, and present our perspective on future development in this area.

scholarly journals Chimerism, the Microenvironment and Control of Leukemia

2021 ◽  
Vol 12 ◽  
Author(s):  
H. Joachim Deeg
Keyword(s):  
Host Cells ◽  
Cell Manipulation ◽  
Malignant Cells ◽  
Host Interactions ◽  
Donor Cells ◽  
Metabolic Products ◽  
Conditioning Regimens ◽  
Modifying Effect ◽  
And Control ◽  
Remarkable Progress

Transplantation of allogeneic hematopoietic cells faces two barriers: failure of engraftment due to a host versus graft reaction, and the attack of donor cells against the patient, the graft versus host (GVH) reaction. This reaction may lead to GVH disease (GVHD), but in patients transplanted due to leukemia or other malignant disorders, this may also convey the benefit of a graft versus leukemia (GVL) effect. The interplay of transplant conditioning with donor and host cells and the environment in the patient is complex. The microbiome, particularly in the intestinal tract, profoundly affects these interactions, directly and via soluble mediators, which also reach other host organs. The microenvironment is further altered by the modifying effect of malignant cells on marrow niches, favoring the propagation of the malignant cells. The development of stable mixed donor/host chimerism has the potential of GVHD prevention without necessarily increasing the risk of relapse. There has been remarkable progress with novel conditioning regimens and selective T-cell manipulation aimed at securing engraftment while preventing GVHD without ablating the GVL effect. Interventions to alter the microenvironment and change the composition of the microbiome and its metabolic products may modify graft/host interactions, thereby further reducing GVHD, while enhancing the GVL effect. The result should be improved transplant outcome.

scholarly journals Probing Molecular Insights of Zika Virus-Host Interactions

2018 ◽  
Author(s):  
Ina Lee ◽  
Sandra Bos ◽  
Ge Li ◽  
Shusheng Wang ◽  
Gilles Gadea ◽  
...  
Keyword(s):  
Viral Entry ◽  
Zika Virus ◽  
Protein Structures ◽  
Fetal Brain ◽  
Protein S ◽  
Cell Receptor ◽  
Host Cells ◽  
Host Interactions ◽  
Neurologic Disorders ◽  
Viral Virulence

The recent Zika virus (ZIKV) outbreak in Americas surprised all of us because of its rapid spread and association with neurologic disorders including fetal microcephaly, brain and ocular anomalies and Guillain-Barr&eacute; syndrome. In responding to this global health outcry, unprecedented and world-wide efforts are taking place to study the ZIKV etiology. Much have been learned about this virus in the areas of epidemiology, clinical manifestation, viral sequences and protein structures, as well as effects of ZIKV infection on fetal brain development and microcephaly. However, the molecular mechanism underlying ZIKV-mediated neurologic disorders remains elusive. Some critical questions include: 1) what type of virologic changes has taken place that increased the viral virulence? 2) which ZIKV protein(s) is responsible for the enhanced viral pathogenicity? And 3) how the newly adapted and pathogenic ZIKV strains alter their interactions with host cells leading to neurologic disorders? The goal of this review is to explore the molecular insights into the ZIKV-host interactions with special focuses on host cell receptor usage for viral entry, host cellular and immune antiviral responses, ZIKV counteraction and ZIKV-induced cytopathic effects. Our hope with this literature review is to inspire additional studies focusing on molecular studies of ZIKV-host Interactions.

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