scholarly journals The Molecular Interplay between Human Coronaviruses and Autophagy

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2022
Author(s):  
Ankit Shroff ◽  
Taras Y. Nazarko
Keyword(s):  
Life Cycle ◽  
Membrane Trafficking ◽  
Molecular Mechanisms ◽  
Membrane Vesicles ◽  
Intracellular Protein ◽  
Double Membrane ◽  
The Past ◽  
Trafficking Pathway ◽  
Life Threatening ◽  
Human Coronaviruses

Coronavirus disease 2019 (COVID-19), caused by a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has instantaneously emerged as a worldwide pandemic. However, humans encountered other coronaviruses in the past, and they caused a broad range of symptoms, from mild to life-threatening, depending on the virus and immunocompetence of the host. Most human coronaviruses interact with the proteins and/or double-membrane vesicles of autophagy, the membrane trafficking pathway that degrades and recycles the intracellular protein aggregates, organelles, and pathogens, including viruses. However, coronaviruses often neutralize and hijack this pathway to complete their life cycle. In this review, we discuss the interactions of human coronaviruses and autophagy, including recent data from SARS-CoV-2-related studies. Some of these interactions (for example, viral block of the autophagosome–lysosome fusion), while being conserved across multiple coronaviruses, are accomplished via different molecular mechanisms. Therefore, it is important to understand the molecular interplay between human coronaviruses and autophagy for developing efficient therapies against coronaviral diseases.

Omegasomes: PI3P platforms that manufacture autophagosomes

2013 ◽  
Vol 55 ◽  
pp. 17-27 ◽  
Author(s):  
Rebecca Roberts ◽  
Nicholas T. Ktistakis
Keyword(s):  
Molecular Mechanisms ◽  
Protein Complexes ◽  
Membrane Vesicles ◽  
Double Membrane ◽  
Survival Pathway ◽  
Membrane Compartments ◽  
Specific Control ◽  
Phosphatidylinositol 3

Autophagy is a conserved survival pathway, which cells and tissues will activate during times of stress. It is characterized by the formation of double-membrane vesicles called autophagosomes inside the cytoplasm. The molecular mechanisms and the signalling components involved require specific control to ensure correct activation. The present chapter describes the formation of autophagosomes from within omegasomes, newly identified membrane compartments enriched in PI3P (phosphatidylinositol 3-phosphate) that serve as platforms for the formation of at least some autophagosomes. We discuss the signalling events required to nucleate the formation of omegasomes as well as the protein complexes involved.

scholarly journals From Genes to Transcripts, a Tightly Regulated Journey in Plasmodium

2020 ◽  
Vol 10 ◽  
Author(s):  
Thomas Hollin ◽  
Karine G. Le Roch
Keyword(s):  
Life Cycle ◽  
Malaria Parasite ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Regulatory Mechanisms ◽  
Tight Control ◽  
Control Of Gene Expression ◽  
Human Malaria Parasite ◽  
Stage Conversion ◽  
The Past

Over the past decade, we have witnessed significant progresses in understanding gene regulation in Apicomplexa including the human malaria parasite, Plasmodium falciparum. This parasite possesses the ability to convert in multiple stages in various hosts, cell types, and environments. Recent findings indicate that P. falciparum is talented at using efficient and complementary molecular mechanisms to ensure a tight control of gene expression at each stage of its life cycle. Here, we review the current understanding on the contribution of the epigenome, atypical transcription factors, and chromatin organization to regulate stage conversion in P. falciparum. The adjustment of these regulatory mechanisms occurring during the progression of the life cycle will be extensively discussed.

scholarly journals Characteristics of the Life Cycle of Porcine Deltacoronavirus (PDCoV) In Vitro: Replication Kinetics, Cellular Ultrastructure and Virion Morphology, and Evidence of Inducing Autophagy

Viruses ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 455 ◽  
Author(s):  
Pan Qin ◽  
En-Zhong Du ◽  
Wen-Ting Luo ◽  
Yong-Le Yang ◽  
Yu-Qi Zhang ◽  
...  
Keyword(s):  
Life Cycle ◽  
Time Course ◽  
Membrane Vesicles ◽  
Infection Cycle ◽  
Genomic Rna ◽  
Double Membrane ◽  
Severe Diarrhea ◽  
Cellular Ultrastructure ◽  
First Time

Porcine deltacoronavirus (PDCoV) causes severe diarrhea and vomiting in affected piglets. The aim of this study was to establish the basic, in vitro characteristics of the life cycle such as replication kinetics, cellular ultrastructure, virion morphology, and induction of autophagy of PDCoV. Time-course analysis of viral subgenomic and genomic RNA loads and infectious titers indicated that one replication cycle of PDCoV takes 5 to 6 h. Electron microscopy showed that PDCoV infection induced the membrane rearrangements with double-membrane vesicles and large virion-containing vacuoles. The convoluted membranes structures described in alpha- and beta-coronavirus were not observed. PDCoV infection also increased the number of autophagosome-like vesicles in the cytoplasm of cells, and the autophagy response was detected by LC3 I/II and p62 Western blot analysis. For the first time, this study presents the picture of the PDCoV infection cycle, which is crucial to help elucidate the molecular mechanism of deltacoronavirus replication.

scholarly journals Mitochondria and Mitochondrial DNA: Key Elements in the Pathogenesis and Exacerbation of the Inflammatory State Caused by COVID-19

Medicina ◽  
2021 ◽  
Vol 57 (9) ◽  
pp. 928
Author(s):  
José J. Valdés-Aguayo ◽  
Idalia Garza-Veloz ◽  
José I. Badillo-Almaráz ◽  
Sofia Bernal-Silva ◽  
Maria C. Martínez-Vázquez ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Viral Genome ◽  
Molecular Mechanisms ◽  
Membrane Vesicles ◽  
Defense System ◽  
Mt Dna ◽  
Double Membrane ◽  
Cell Defense ◽  
Inflammatory State ◽  
Potential Area

Background and Objectives. The importance of mitochondria in inflammatory pathologies, besides providing energy, is associated with the release of mitochondrial damage products, such as mitochondrial DNA (mt-DNA), which may perpetuate inflammation. In this review, we aimed to show the importance of mitochondria, as organelles that produce energy and intervene in multiple pathologies, focusing mainly in COVID-19 and using multiple molecular mechanisms that allow for the replication and maintenance of the viral genome, leading to the exacerbation and spread of the inflammatory response. The evidence suggests that mitochondria are implicated in the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which forms double-membrane vesicles and evades detection by the cell defense system. These mitochondrion-hijacking vesicles damage the integrity of the mitochondrion’s membrane, releasing mt-DNA into circulation and triggering the activation of innate immunity, which may contribute to an exacerbation of the pro-inflammatory state. Conclusions. While mitochondrial dysfunction in COVID-19 continues to be studied, the use of mt-DNA as an indicator of prognosis and severity is a potential area yet to be explored.

scholarly journals The dendritic cell side of the immunological synapse

2016 ◽  
Vol 7 (1) ◽  
pp. 17-28 ◽  
Author(s):  
Danielle R.J. Verboogen ◽  
Ilse Dingjan ◽  
Natalia H. Revelo ◽  
Linda J. Visser ◽  
Martin ter Beest ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mhc Class I ◽  
Membrane Trafficking ◽  
Molecular Mechanisms ◽  
Immunological Synapse ◽  
Membrane Vesicles ◽  
Class I ◽  
Lytic Granules ◽  
Mhc Molecules

AbstractImmune responses are initiated by the interactions between antigen-presenting cells (APCs), such as dendritic cells (DCs), with responder cells, such as T cells, via a tight cellular contact interface called the immunological synapse. The immunological synapse is a highly organized subcellular structure that provides a platform for the presentation of antigen in major histocompatibility class I and II complexes (MHC class I and II) on the surface of the APC to receptors on the surface of the responder cells. In T cells, these contacts lead to highly polarized membrane trafficking that results in the local release of lytic granules and in the delivery and recycling of T cell receptors at the immunological synapse. Localized trafficking also occurs at the APC side of the immunological synapse, especially in DCs where antigen loaded in MHC class I and II is presented and cytokines are released specifically at the synapse. Whereas the molecular mechanisms underlying polarized membrane trafficking at the T cell side of the immunological synapse are increasingly well understood, these are still very unclear at the APC side. In this review, we discuss the organization of the APC side of the immunological synapse. We focus on the directional trafficking and release of membrane vesicles carrying MHC molecules and cytokines at the immunological synapses of DCs. We hypothesize that the specific delivery of MHC and the release of cytokines at the immunological synapse mechanistically resemble that of lytic granule release from T cells.

scholarly journals Glycine-zipper motifs in hepatitis C virus nonstructural protein 4B are required for the establishment of viral replication organelles

2017 ◽  
pp. JVI.01890-17 ◽  
Author(s):  
David Paul ◽  
Vanesa Madan ◽  
Omar Ramirez ◽  
Maja Bencun ◽  
Ina Karen Stoeck ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Molecular Mechanisms ◽  
Nonstructural Protein ◽  
Membrane Vesicles ◽  
Rna Replication ◽  
Viral Rna ◽  
Transmembrane Helices ◽  
Double Membrane

Hepatitis C virus (HCV) RNA replication occurs in tight association with remodeled host cell membranes, presenting as cytoplasmic accumulations of single, double and multi membrane vesicles in infected cells. Formation of these so-called replication organelles is mediated by a complex interplay of host cell factors and viral replicase proteins. Of these, nonstructural protein 4B (NS4B), an integral transmembrane protein, appears to play a key role, but little is known about the molecular mechanisms how this protein contributes to organelle biogenesis. Using forward and reverse genetics we identified glycine-zipper motifs within transmembrane helices 2 and 3 of NS4B that are critically involved in viral RNA replication. Foerster resonance energy transfer analysis revealed the importance of the glycine-zippers in NS4B homo and heterotypic self-interactions. Additionally, ultrastructural analysis using electron microscopy unraveled a prominent role of glycine-zipper residues for the subcellular distribution and the morphology of HCV-induced double membrane vesicles. Notably, loss-of-function NS4B glycine-zipper mutants prominently induced single membrane vesicles with secondary invaginations that might represent an arrested intermediate state in double membrane vesicle formation. These findings highlight a so far unknown role of glycine residues within the membrane integral core domain for NS4B self-interaction and functional as well as structural integrity of HCV replication organelles.IMPORTANCERemodeling of the cellular endomembrane system leading to the establishment of replication organelles is a hallmark of positive-strand RNA viruses. In the case of hepatitis C virus (HCV), expression of the nonstructural proteins induces the accumulation of double membrane vesicles that likely arise from a concerted action of viral and co-opted cellular factors. However, the underlying molecular mechanisms are incompletely understood. Here, we identify glycine-zipper motifs within HCV nonstructural protein 4B (NS4B) transmembrane segments 2 and 3 that are crucial for the protein's self-interaction. Moreover, glycine residues within NS4B transmembrane helices critically contribute to the biogenesis of functional replication organelles and thus, efficient viral RNA replication. These results reveal how glycine-zipper motifs in NS4B contribute to structural and functional integrity of the HCV replication organelles and thus, viral RNA replication.

scholarly journals Autophagy regulation by acetylation—implications for neurodegenerative diseases

2021 ◽  
Vol 53 (1) ◽  
pp. 30-41
Author(s):  
Sung Min Son ◽  
So Jung Park ◽  
Marian Fernandez-Estevez ◽  
David C. Rubinsztein
Keyword(s):  
Neurodegenerative Diseases ◽  
Posttranslational Modifications ◽  
Molecular Mechanisms ◽  
Membrane Vesicles ◽  
Cell Types ◽  
Double Membrane ◽  
Physiological Processes ◽  
Evolutionarily Conserved ◽  
Development And Aging ◽  
Catabolic Process

AbstractPosttranslational modifications of proteins, such as acetylation, are essential for the regulation of diverse physiological processes, including metabolism, development and aging. Autophagy is an evolutionarily conserved catabolic process that involves the highly regulated sequestration of intracytoplasmic contents in double-membrane vesicles called autophagosomes, which are subsequently degraded after fusing with lysosomes. The roles and mechanisms of acetylation in autophagy control have emerged only in the last few years. In this review, we describe key molecular mechanisms by which previously identified acetyltransferases and deacetylases regulate autophagy. We highlight how p300 acetyltransferase controls mTORC1 activity to regulate autophagy under starvation and refeeding conditions in many cell types. Finally, we discuss how altered acetylation may impact various neurodegenerative diseases in which many of the causative proteins are autophagy substrates. These studies highlight some of the complexities that may need to be considered by anyone aiming to perturb acetylation under these conditions.

The Evolution of Lead Extraction

2009 ◽  
Vol 5 (1) ◽  
pp. 32
Author(s):  
Melanie Maytin ◽  
Laurence M Epstein ◽  
◽  
Keyword(s):  
Natural Selection ◽  
Lead Extraction ◽  
Significant Morbidity ◽  
Extraction Techniques ◽  
Extraction Technology ◽  
Device Management ◽  
Future Developments ◽  
The Past ◽  
New Methods ◽  
Life Threatening

Prior to the introduction of successful intravascular countertraction techniques, options for lead extraction were limited and dedicated tools were non-existent. The significant morbidity and mortality associated with these early extraction techniques limited their application to life-threatening situations such as infection and sepsis. The past 30 years have witnessed significant advances in lead extraction technology, resulting in safer and more efficacious techniques and tools. This evolution occurred out of necessity, similar to the pressure of natural selection weeding out the ineffective and highly morbid techniques while fostering the development of safe, successful and more simple methods. Future developments in lead extraction are likely to focus on new tools that will allow us to provide comprehensive device management and the design of new leads conceived to facilitate future extraction. With the development of these new methods and novel tools, the technique of lead extraction will continue to require operators that are well versed in several methods of extraction. Garnering new skills while remembering the lessons of the past will enable extraction technologies to advance without repeating previous mistakes.

Brain-eating Amoebae Infection: Challenges and Opportunities in Chemotherapy

2019 ◽  
Vol 19 (12) ◽  
pp. 980-987 ◽  
Author(s):  
Mohammad Ridwane Mungroo ◽  
Ayaz Anwar ◽  
Naveed Ahmed Khan ◽  
Ruqaiyyah Siddiqui
Keyword(s):  
Mortality Rate ◽  
Free Living ◽  
Outdoor Activities ◽  
The Past ◽  
Free Living Amoeba ◽  
Challenges And Opportunities ◽  
Life Threatening ◽  
The Central Nervous System ◽  
Living Nature ◽  
Treatment And Diagnosis

Pathogenic free-living amoeba are known to cause a devastating infection of the central nervous system and are often referred to as “brain-eating amoebae”. The mortality rate of more than 90% and free-living nature of these amoebae is a cause for concern. It is distressing that the mortality rate has remained the same over the past few decades, highlighting the lack of interest by the pharmaceutical industry. With the threat of global warming and increased outdoor activities of public, there is a need for renewed interest in identifying potential anti-amoebic compounds for successful prognosis. Here, we discuss the available chemotherapeutic options and opportunities for potential strategies in the treatment and diagnosis of these life-threatening infections.

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