scholarly journals Evolution of a single-cell predictive model for packaging and budding of viruses based on TEM based measurements

2021 ◽  
Author(s):  
Abha Saxena ◽  
Ravutla Suryateja ◽  
Kishalay Mitra ◽  
Jayanta Chakraborty ◽  
David Murhammer ◽  
...  
Keyword(s):  
Parameter Estimation ◽  
Predictive Model ◽  
Viral Infections ◽  
Experimental Investigations ◽  
Computational Framework ◽  
Transmission Electron ◽  
Feedback Structure ◽  
Infected Cells ◽  
Production Building ◽  
Budded Virus

Although detailed experimental investigations would provide insight into viral infections and vaccine production, building a computational framework is necessary to identify the parameters that regulate the budding and packaging of nucleocapsids. This study shows that a predictive model for the complete infection cycle can be built using nonlinear coupled ODEs and parameter estimation using a Genetic algorithm. Specifically, we have used a dataset containing the occluded virus information, budded virus in infected cells obtained by transmission electron microscopy (TEM). A novel parameter estimation strategy is proposed based on the k-medoid clustering of infected cells. Firstly, we show that the parameter estimation framework can be used for model evolution and selection of the feedback structure. Secondly, we show that the model was capable of capturing the distribution of packaged and unpackaged nucleocapsids in the nucleus, cytoplasm, and plasma membrane, the number of packaged and unpackaged ODV, and polyhedra in the nucleus. The proposed framework assumes importance in generating data for achieving quality by design in the optimization of vaccine/recombinant protein yield.

scholarly journals Immunosurveillance of Cancer and Viral Infections with Regard to Alterations of Human NK Cells Originating from Lifestyle and Aging

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 557
Author(s):  
Xuewen Deng ◽  
Hiroshi Terunuma ◽  
Mie Nieda
Keyword(s):  
Nk Cells ◽  
Viral Infections ◽  
Nk Cell ◽  
Healthy Lifestyle ◽  
Cell Activity ◽  
Nk Cell Activity ◽  
Effector Cells ◽  
Cell Dysfunction ◽  
Forest Bathing ◽  
Infected Cells

Natural killer (NK) cells are cytotoxic immune cells with an innate capacity for eliminating cancer cells and virus- infected cells. NK cells are critical effector cells in the immunosurveillance of cancer and viral infections. Patients with low NK cell activity or NK cell deficiencies are predisposed to increased risks of cancer and severe viral infections. However, functional alterations of human NK cells are associated with lifestyles and aging. Personal lifestyles, such as cigarette smoking, alcohol consumption, stress, obesity, and aging are correlated with NK cell dysfunction, whereas adequate sleep, moderate exercise, forest bathing, and listening to music are associated with functional healthy NK cells. Therefore, adherence to a healthy lifestyle is essential and will be favorable for immunosurveillance of cancer and viral infections with healthy NK cells.

scholarly journals Poxviral Strategies to Overcome Host Cell Apoptosis

Pathogens ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 6
Author(s):  
Chathura D. Suraweera ◽  
Mark G. Hinds ◽  
Marc Kvansakul
Keyword(s):  
Viral Infections ◽  
B Cell Lymphoma ◽  
Intrinsic Apoptosis ◽  
Host Cell Apoptosis ◽  
Successful Infection ◽  
Infected Cells ◽  
Host Virus Interactions ◽  
Almost All ◽  
Virus Interactions ◽  
Multicellular Organisms

Apoptosis is a form of cellular suicide initiated either via extracellular (extrinsic apoptosis) or intracellular (intrinsic apoptosis) cues. This form of programmed cell death plays a crucial role in development and tissue homeostasis in multicellular organisms and its dysregulation is an underlying cause for many diseases. Intrinsic apoptosis is regulated by members of the evolutionarily conserved B-cell lymphoma-2 (Bcl-2) family, a family that consists of pro- and anti-apoptotic members. Bcl-2 genes have also been assimilated by numerous viruses including pox viruses, in particular the sub-family of chordopoxviridae, a group of viruses known to infect almost all vertebrates. The viral Bcl-2 proteins are virulence factors and aid the evasion of host immune defenses by mimicking the activity of their cellular counterparts. Viral Bcl-2 genes have proved essential for the survival of virus infected cells and structural studies have shown that though they often share very little sequence identity with their cellular counterparts, they have near-identical 3D structures. However, their mechanisms of action are varied. In this review, we examine the structural biology, molecular interactions, and detailed mechanism of action of poxvirus encoded apoptosis inhibitors and how they impact on host–virus interactions to ultimately enable successful infection and propagation of viral infections.

scholarly journals Mass Spectrometry versus Conventional Techniques of Protein Detection: Zika Virus NS3 Protease Activity towards Cellular Proteins

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3732
Author(s):  
Agnieszka Dabrowska ◽  
Aleksandra Milewska ◽  
Joanna Ner-Kluza ◽  
Piotr Suder ◽  
Krzysztof Pyrc
Keyword(s):  
Mass Spectrometry ◽  
Zika Virus ◽  
Viral Infections ◽  
Protein Detection ◽  
Extensive Discussion ◽  
Protein Targets ◽  
Highly Sensitive ◽  
Infected Cells ◽  
Ns3 Protease ◽  
To Receive

Mass spectrometry (MS) used in proteomic approaches is able to detect hundreds of proteins in a single assay. Although undeniable high analytical power of MS, data acquired sometimes lead to confusing results, especially during a search of very selective, unique interactions in complex biological matrices. Here, we would like to show an example of such confusing data, providing an extensive discussion on the observed phenomenon. Our investigations focus on the interaction between the Zika virus NS3 protease, which is essential for virus replication. This enzyme is known for helping to remodel the microenvironment of the infected cells. Several reports show that this protease can process cellular substrates and thereby modify cellular pathways that are important for the virus. Herein, we explored some of the targets of NS3, clearly shown by proteomic techniques, as processed during infection. Unfortunately, we could not confirm the biological relevance of protein targets for viral infections detected by MS. Thus, although mass spectrometry is highly sensitive and useful in many instances, also being able to show directions where cell/virus interaction occurs, we believe that deep recognition of their biological role is essential to receive complete insight into the investigated process.

scholarly journals Thermodynamic Modelling and Microstructural Study of Z-Phase Formation in a Ta-Alloyed Martensitic Steel

Materials ◽  
2021 ◽  
Vol 14 (6) ◽  
pp. 1332
Author(s):  
Florian Riedlsperger ◽  
Bernadette Gsellmann ◽  
Erwin Povoden-Karadeniz ◽  
Oriana Tassa ◽  
Susanna Matera ◽  
...  
Keyword(s):  
Special Focus ◽  
Scanning Calorimetry ◽  
Transmission Electron Microscopy Analysis ◽  
Computational Framework ◽  
Mobility Data ◽  
Interfacial Energies ◽  
Transmission Electron ◽  
Size Number ◽  
Electron Microscopy Analysis ◽  
Microscopy Analysis

A thermokinetic computational framework for precipitate transformation simulations in Ta-containing martensitic Z-steels was developed, including Calphad thermodynamics, diffusion mobility data from the literature, and a kinetic parameter setup that considered precipitation sites, interfacial energies and dislocation density evolution. The thermodynamics of Ta-containing subsystems were assessed by atomic solubility data and enthalpies from the literature as well as from the experimental dissolution temperature of Ta-based Z-phase CrTaN obtained from differential scanning calorimetry. Accompanied by a comprehensive transmission electron microscopy analysis of the microstructure, thermokinetic precipitation simulations with a wide-ranging and well-documented set of input parameters were carried out in MatCalc for one sample alloy. A special focus was placed on modelling the transformation of MX into the Z-phase, which was driven by Cr diffusion. The simulation results showed excellent agreement with experimental data in regard to size, number density and chemical composition of the precipitates, showing the usability of the developed thermokinetic simulation framework.

scholarly journals Functional analysis of the putative antiapoptotic genes, p49 and iap4, of Spodoptera litura nucleopolyhedrovirus with RNAi

2008 ◽  
Vol 89 (8) ◽  
pp. 1873-1880 ◽  
Author(s):  
Qian Yu ◽  
Tiehao Lin ◽  
Guozhong Feng ◽  
Kai Yang ◽  
Yi Pang
Keyword(s):  
Spodoptera Litura ◽  
Virus Production ◽  
Host Cells ◽  
Homology Search ◽  
Pcr Analysis ◽  
Viability Analysis ◽  
Infected Cells ◽  
Budded Virus ◽  
Almost All

A homology search of a public database revealed that Spodoptera litura nucleopolyhedrovirus (SpltNPV) possesses two putative, antiapoptotic genes, p49 and inhibitor of apoptosis 4 (iap4), but their function has not been investigated in its native host cells. In the present study, we used RNA interference (RNAi) to silence the expression of Splt-iap4 and Splt-p49, independently or together, to determine their roles during the SpltNPV life cycle. RT-PCR analysis and Western blot analysis showed the target gene expression had been knocked out in the SpltNPV-infected SpLi-221 cells after treatment with Splt-p49 or Splt-iap4 double-stranded RNA (dsRNA), respectively, confirming that the two genes were effectively silenced. In SpltNPV-infected cells treated with Splt-p49 dsRNA, apoptosis was observed beginning at 14 h, and almost all cells had undergone apoptosis by 48 h. In contrast, budded virus production and polyhedra formation progressed normally in infected cells treated with Splt-iap4 dsRNA. Cell viability analysis showed that Splt-IAP4 had no synergistic effect on the inhibition of apoptosis of SpLi-221 cells induced by SpltNPV infection. Interestingly, after Splt-iap4 dsRNA treatment, cells did not congregate like those infected with SpltNPV in the early infection phase, implying an unknown role of baculovirus iap4. Our results determine that Splt-p49 is necessary to prevent apoptosis; however, Splt-iap4 has no antiapoptotic function during SpltNPV infection.

scholarly journals Effect of the preparation Ingavirin® (imidazolyl ethanamide pentandioic acid) on the interferon status of cells under conditions of viral infection

2016 ◽  
Vol 21 (4) ◽  
pp. 196-205
Author(s):  
Thomas Aschacher ◽  
Artem Krokhin ◽  
Irina Kuznetsova ◽  
Johannes Langle ◽  
Vladimir Nebolsin ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Viral Infection ◽  
Viral Infections ◽  
Antiviral Drug ◽  
Effector Proteins ◽  
Theoretical Ground ◽  
Ns1 Protein ◽  
Interferon Inducer ◽  
Infected Cells ◽  
Interferon System

Ingavirin® (imidazolyl ethanamide pentandioic acid) is an original antiviral drug, which is used in Russia for treatment and profilaxis of influenza and other acute viral infections. We confirmed that imidazolyl ethanamide pentandioic acid (IEPA), not being interferon inducer itself, enhances synthesis of both interferon-a/fi receptors (IFNAR) to interferone and cell sensitivity to interferone signalling, which was suppressed by NS1 protein - pathogen factor of influenza virus. IEPA is able to promote antiviral effector proteins PKR and MxA in infected cells, in opposition to interferon system suppression by influenza virus. Theoretical ground of clinical efficacy of Ingavirine® could be confirmed by obtained data of influence to innate immune system during viral infection.

scholarly journals Transcriptional role of p53 in interferon-mediated antiviral immunity

2008 ◽  
Vol 205 (8) ◽  
pp. 1929-1938 ◽  
Author(s):  
César Muñoz-Fontela ◽  
Salvador Macip ◽  
Luis Martínez-Sobrido ◽  
Lauren Brown ◽  
Joseph Ashour ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Viral Replication ◽  
Viral Infections ◽  
Suppressor Gene ◽  
Central Component ◽  
Type I ◽  
Infected Cells

Tumor suppressor p53 is activated by several stimuli, including DNA damage and oncogenic stress. Previous studies (Takaoka, A., S. Hayakawa, H. Yanai, D. Stoiber, H. Negishi, H. Kikuchi, S. Sasaki, K. Imai, T. Shibue, K. Honda, and T. Taniguchi. 2003. Nature. 424:516–523) have shown that p53 is also induced in response to viral infections as a downstream transcriptional target of type I interferon (IFN) signaling. Moreover, many viruses, including SV40, human papillomavirus, Kaposi's sarcoma herpesvirus, adenoviruses, and even RNA viruses such as polioviruses, have evolved mechanisms designated to abrogate p53 responses. We describe a novel p53 function in the activation of the IFN pathway. We observed that infected mouse and human cells with functional p53 exhibited markedly decreased viral replication early after infection. This early inhibition of viral replication was mediated both in vitro and in vivo by a p53-dependent enhancement of IFN signaling, specifically the induction of genes containing IFN-stimulated response elements. Of note, p53 also contributed to an increase in IFN release from infected cells. We established that this p53-dependent enhancement of IFN signaling is dependent to a great extent on the ability of p53 to activate the transcription of IFN regulatory factor 9, a central component of the IFN-stimulated gene factor 3 complex. Our results demonstrate that p53 contributes to innate immunity by enhancing IFN-dependent antiviral activity independent of its functions as a proapoptotic and tumor suppressor gene.

scholarly journals Double trouble: combined cardiovascular effects of particulate matter exposure and coronavirus disease 2019

2020 ◽  
Author(s):  
Vineeta Tanwar ◽  
Jeremy M Adelstein ◽  
Loren E Wold
Keyword(s):  
Particulate Matter ◽  
Viral Infections ◽  
Inflammatory Responses ◽  
Angiotensin Receptor Blockers ◽  
Cardiovascular Effects ◽  
Air Pollutant ◽  
The Body ◽  
Experimental Investigations ◽  
Cardiac Complications ◽  
Converting Enzyme Inhibitors

Abstract The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly grown into a pandemic. According to initial reports, the lungs were thought to be the primary target, but recent case studies have shown its reach can extend to other organs including the heart and blood vessels. The severity of cardiac complications of COVID-19 depends on multiple underlying factors, with air pollutant exposure being one of them, as reported by several recent studies. Airborne particulate matter (PM) attracts heightened attention due to its implication in various diseases, especially respiratory and cardiovascular diseases. Inhaled PM not only carries microorganisms inside the body but also elicits local and systemic inflammatory responses resulting in altering the host’s immunity and increasing susceptibility to infection. Previous and recent studies have documented that PM acts as a ‘carrier’ for the virus and aids in spreading viral infections. This review presents the mechanisms and effects of viral entry and how pollution can potentially modulate pathophysiological processes in the heart. We aimed to concisely summarize studies examining cardiovascular outcomes in COVID-19 patients and postulate on how PM can influence these outcomes. We have also reviewed evidence on the use of renin–angiotensin system inhibitors, namely angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, in patients with COVID-19. The interplay of pollution and SARS-CoV-2 is essential to understanding the effects of accentuated cardiovascular effects of COVID-19 and deserves in-depth experimental investigations.

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