scholarly journals The diverse roles and dynamic rearrangement of vimentin during viral infection

2020 ◽  
Vol 134 (5) ◽  
pp. jcs250597
Author(s):  
Yue Zhang ◽  
Zeyu Wen ◽  
Xuemeng Shi ◽  
Yan-Jun Liu ◽  
John E. Eriksson ◽  
...  
Keyword(s):  
Life Cycle ◽  
Viral Infection ◽  
Host Cell ◽  
Cell Biology ◽  
Viral Infections ◽  
Epithelial Mesenchymal Transition ◽  
Regulation Of Expression ◽  
Mesenchymal Transition ◽  
Cell Defense ◽  
Interaction Sites

ABSTRACTEpidemics caused by viral infections pose a significant global threat. Cytoskeletal vimentin is a major intermediate filament (IF) protein, and is involved in numerous functions, including cell signaling, epithelial–mesenchymal transition, intracellular organization and cell migration. Vimentin has important roles for the life cycle of particular viruses; it can act as a co-receptor to enable effective virus invasion and guide efficient transport of the virus to the replication site. Furthermore, vimentin has been shown to rearrange into cage-like structures that facilitate virus replication, and to recruit viral components to the location of assembly and egress. Surprisingly, vimentin can also inhibit virus entry or egress, as well as participate in host-cell defense. Although vimentin can facilitate viral infection, how this function is regulated is still poorly understood. In particular, information is lacking on its interaction sites, regulation of expression, post-translational modifications and cooperation with other host factors. This Review recapitulates the different functions of vimentin in the virus life cycle and discusses how they influence host-cell tropism, virulence of the pathogens and the consequent pathological outcomes. These insights into vimentin–virus interactions emphasize the importance of cytoskeletal functions in viral cell biology and their potential for the identification of novel antiviral targets.

scholarly journals An Integrated View of Virus-Triggered Cellular Plasticity Using Boolean Networks

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2863
Author(s):  
Jenny Paola Alfaro-García ◽  
María Camila Granados-Alzate ◽  
Miguel Vicente-Manzanares ◽  
Juan Carlos Gallego-Gómez
Keyword(s):  
Cell Biology ◽  
Epithelial Mesenchymal Transition ◽  
Boolean Networks ◽  
Cellular Plasticity ◽  
Mortality And Morbidity ◽  
Mesenchymal Transition ◽  
Logical Operators ◽  
Cell Tissue ◽  
Resource Exhaustion ◽  
Modeling Data

Virus-related mortality and morbidity are due to cell/tissue damage caused by replicative pressure and resource exhaustion, e.g., HBV or HIV; exaggerated immune responses, e.g., SARS-CoV-2; and cancer, e.g., EBV or HPV. In this context, oncogenic and other types of viruses drive genetic and epigenetic changes that expand the tumorigenic program, including modifications to the ability of cancer cells to migrate. The best-characterized group of changes is collectively known as the epithelial–mesenchymal transition, or EMT. This is a complex phenomenon classically described using biochemistry, cell biology and genetics. However, these methods require enormous, often slow, efforts to identify and validate novel therapeutic targets. Systems biology can complement and accelerate discoveries in this field. One example of such an approach is Boolean networks, which make complex biological problems tractable by modeling data (“nodes”) connected by logical operators. Here, we focus on virus-induced cellular plasticity and cell reprogramming in mammals, and how Boolean networks could provide novel insights into the ability of some viruses to trigger uncontrolled cell proliferation and EMT, two key hallmarks of cancer.

scholarly journals Characterization of Symbiodinium-associated viruses and implications for coral health

2021 ◽  
Author(s):  
◽  
Scott Anthony Lawrence
Keyword(s):  
Viral Infection ◽  
Host Cell ◽  
Cell Cultures ◽  
Viral Infections ◽  
Lytic Cycle ◽  
Symbiodinium Cell ◽  
Coral Diseases ◽  
Expression Levels ◽  
Virus Like Particles ◽  
Chronic Viral Infections

<p>Coral reefs are in decline worldwide. Much of this decline is attributable to mass coral bleaching events and disease outbreaks, both of which are linked to anthropogenic climate change. Despite increased research effort, much remains unknown about these phenomena, especially the causative agents of many coral diseases. In particular, coral-associated viruses have received little attention, and their potential roles in coral diseases are largely unknown. This study aimed to address this lack of information by characterising the viruses associated with reef-building corals and Symbiodinium (dinoflagellates that can form symbioses with corals).  Symbiodinium virus screening experiments revealed the presence of numerous and varied virus-like particles (VLPs) inside cells. Of the 49 Symbiodinium cultures screened, approximately one third contained putative latent viral infections that could be induced to enter their lytic cycle by UV irradiation. Electron microscope examination revealed VLPs closely resembling viruses previously found in dinoflagellates and other microalgae. Three cultures that showed evidence of latent viral infections were chosen for whole transcriptome sequencing, which revealed the presence of viral genes that were expressed in several different types of Symbiodinium. The relationship between the detected genes and known viral gene sequences suggested that the cells were infected with double-stranded DNA (dsDNA) viruses.  In order to determine how the host cell responds to stress-induced viral infection, the expression levels of genes associated with stress response and viral infection were measured. The expression levels of many genes were unchanged following UV stress, and expression of genes that were predicted to be upregulated following stress, such as those encoding antioxidant enzymes, in fact showed lower expression levels. Despite this, several groups of genes involved in viral infection and host cell response were upregulated following stress, providing further evidence for stress-induced latent or chronic viral infections.  In addition to the research carried out on Symbiodinium cell cultures, viruses associated with three coral diseases were studied using electron microscopy. Virus-like particles were present in coral and Symbiodinium cells from all three diseases, but viral abundance was correlated with disease state in only one: white patch syndrome (WPS) of Porites australiensis. The locations and morphologies of the VLPs associated with WPS suggested the presence of dsDNA and single-stranded RNA (ssRNA) viruses infecting both the coral animal and Symbiodinium cells. DNA sequences obtained from WPS-affected corals matched closely with sequences obtained from VLP-containing Symbiodinium cells. Based on the evidence gathered from Symbiodinium cell cultures and coral tissues, I propose a theoretical model of viral infection in WPS. In this model, the coral animal cells are routinely subject to chronic viral infections, and Symbiodinium cells harbour two types of chronic or latent infections – a dsDNA and an ssRNA virus – that can be induced via stress, resulting in cell lysis or loss of the cells from the coral host.  In addition to detection and rudimentary identification of viruses infecting Symbiodinium cells, this study generated the largest dinoflagellate transcriptomic dataset to date. These data will prove valuable for future research into Symbiodinium, both in terms of viral infections and more generally.</p>

scholarly journals Epithelial to Mesenchymal Transition and Cell Biology of Molecular Regulation in Endometrial Carcinogenesis

2019 ◽  
Vol 8 (4) ◽  
pp. 439 ◽  
Author(s):  
Hsiao-Chen Chiu ◽  
Chia-Jung Li ◽  
Giou-Teng Yiang ◽  
Andy Tsai ◽  
Meng-Yu Wu
Keyword(s):  
Growth Factor ◽  
Signaling Pathways ◽  
Cell Biology ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Cell Metabolism ◽  
Basic Research ◽  
Genetic Mutation ◽  
Molecular Regulation ◽  
Mesenchymal Transition

Endometrial carcinogenesis is involved in several signaling pathways and it comprises multiple steps. The four major signaling pathways—PI3K/AKT, Ras/Raf/MEK/ERK, WNT/β-catenin, and vascular endothelial growth factor (VEGF)—are involved in tumor cell metabolism, growth, proliferation, survival, and angiogenesis. The genetic mutation and germline mitochondrial DNA mutations also impair cell proliferation, anti-apoptosis signaling, and epithelial–mesenchymal transition by several transcription factors, leading to endometrial carcinogenesis and distant metastasis. The PI3K/AKT pathway activates the ransforming growth factor beta (TGF-β)-mediated endothelial-to-mesenchymal transition (EMT) and it interacts with downstream signals to upregulate EMT-associated factors. Estrogen and progesterone signaling in EMT also play key roles in the prognosis of endometrial carcinogenesis. In this review article, we summarize the current clinical and basic research efforts regarding the detailed molecular regulation in endometrial carcinogenesis, especially in EMT, to provide novel targets for further anti-carcinogenesis treatment.

The Cell Biology of SARS-CoV-2

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Anthony Futerman
Keyword(s):  
Life Cycle ◽  
Critical Point ◽  
Host Cell ◽  
Basic Science ◽  
Cell Biology ◽  
Science Research ◽  
Host Cells ◽  
Biological Features ◽  
Basic Science Research

The critical point in the life cycle of a virus is gaining entry into a host cell so that the virus can replicate. Anthony Futerman describes the distinct biological features of SARS-CoV-2, including its method of entering host cells. He finally urges more support for basic science research so that future biologists will be better prepared to stem diseases before they reach pandemic proportions.

Retinoic Acid Inducible Gene-I like Receptors Activate Snail to Limit RNA Viral Infections

2021 ◽  
Author(s):  
Dhiviya Vedagiri ◽  
Divya Gupta ◽  
Anurag Mishra ◽  
Gayathri Krishna ◽  
Meenakshi Bhaskar ◽  
...  
Keyword(s):  
Viral Infections ◽  
Epithelial Mesenchymal Transition ◽  
Ectopic Expression ◽  
Antiviral Response ◽  
Poly I:C ◽  
Type I ◽  
Type I Ifn ◽  
Mesenchymal Transition ◽  
Type I Ifns ◽  
General Response

RLRs are important cytosolic PRRs that sense viral RNA before mounting a response leading to the activation of Type-I IFNs. Several viral infections induce epithelial-mesenchymal transition (EMT), even as its significance remains unclear. Here, we describe that EMT or EMT like process is a general response to viral infections. Our studies identify a previously unknown mechanism of regulation of an important EMT-TF Snail during RNA viral infections, and describe its possible implication. RNA viral infections, poly (I:C) transfection, and ectopic expression of RLR components induced Snail levels, indicating that RLR pathway could regulate its expression. Detailed examination using MAVS-KO cells established that MAVS is essential in this regulation. We identified two ISREs in SNAI1 promoter region and demonstrated that they are important in its transcriptional activation by phosphorylated IRF3. Increasing the levels of Snail activated RLR pathway and dramatically limited replication of RNA viruses DENV, JEV and VSV, pointing to their antiviral functions. Knock-down of Snail resulted in considerable increase in JEV titer, validating its antiviral functions. Finally, TGF-β mediated IFNB activation was dependent on Snail levels, confirming its important role in Type-I IFN activation. Thus, EMT-TF Snail is transcriptionally co-regulated with Type-I IFN by RLRs and in turn promotes RLR pathway, further strengthening the antiviral state in the cell. Our work identified an interesting mechanism of regulation of Snail that demonstrates potential co-regulation of multiple innate antiviral pathways triggered by RLRs. Identification of antiviral functions of Snail also provides an opportunity to expand the sphere of RLR signaling. IMPORTANCE RLRs sense viral genomic RNA or the dsRNA intermediates and trigger the activation of Type I IFNs. Snail transcription factor, commonly associated with epithelial-mesenchymal transition, has been reported to facilitate EMT in several viral infections. Much of these reports come from oncoviruses, leading to the speculation that EMT induced during infection is an important factor in the oncogenesis triggered by these infections. However, our studies reveal that EMT or EMT like processes during viral infections have important functions in antiviral response. We have characterized a new mechanism of transcriptional regulation of Snail by IRF3 through ISRE in their promoters and this finding could have importance in non-viral contexts as well. We also identify that EMT-TF Snail promotes antiviral status of the infected cells through RLR pathway. This work characterizes a new regulatory mechanism of activation of Snail and establishes its unidentified function in antiviral response.

scholarly journals When MARCH family proteins meet viral infections

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Chunfu Zheng ◽  
Yan-Dong Tang
Keyword(s):  
Life Cycle ◽  
Viral Infection ◽  
Viral Infections ◽  
Ring Finger ◽  
Ubiquitin Ligases ◽  
Viral Life Cycle ◽  
Ring Finger Domain ◽  
E3 Ligases

AbstractMembrane-associated RING-CH (MARCH) ubiquitin ligases belong to a RING finger domain E3 ligases family. Recent studies have demonstrated that MARCH proteins play critical roles during various viral infections. MARCH proteins can directly antagonize different steps of the viral life cycle and promote individual viral infection. This mini-review will focus on the latest advances of MARCH family proteins' emerging roles during viral infections.

scholarly journals The epithelial–mesenchymal transition: new insights in signaling, development, and disease

2006 ◽  
Vol 172 (7) ◽  
pp. 973-981 ◽  
Author(s):  
Jonathan M. Lee ◽  
Shoukat Dedhar ◽  
Raghu Kalluri ◽  
Erik W. Thompson
Keyword(s):  
Cell Biology ◽  
Epithelial Mesenchymal Transition ◽  
International Association ◽  
Mesenchymal Cell ◽  
Potential Contribution ◽  
Mesenchymal Transition ◽  
Scientific Debate ◽  
Pathway Activation ◽  
High Level

The conversion of an epithelial cell to a mesenchymal cell is critical to metazoan embryogenesis and a defining structural feature of organ development. Current interest in this process, which is described as an epithelial–mesenchymal transition (EMT), stems from its developmental importance and its involvement in several adult pathologies. Interest and research in EMT are currently at a high level, as seen by the attendance at the recent EMT meeting in Vancouver, Canada (October 1–3, 2005). The meeting, which was hosted by The EMT International Association, was the second international EMT meeting, the first being held in Port Douglas, Queensland, Australia in October 2003. The EMT International Association was formed in 2002 to provide an international body for those interested in EMT and the reverse process, mesenchymal–epithelial transition, and, most importantly, to bring together those working on EMT in development, cancer, fibrosis, and pathology. These themes continued during the recent meeting in Vancouver. Discussion at the Vancouver meeting spanned several areas of research, including signaling pathway activation of EMT and the transcription factors and gene targets involved. Also covered in detail was the basic cell biology of EMT and its role in cancer and fibrosis, as well as the identification of new markers to facilitate the observation of EMT in vivo. This is particularly important because the potential contribution of EMT during neoplasia is the subject of vigorous scientific debate (Tarin, D., E.W. Thompson, and D.F. Newgreen. 2005. Cancer Res. 65:5996–6000; Thompson, E.W., D.F. Newgreen, and D. Tarin. 2005. Cancer Res. 65:5991–5995).

scholarly journals Immunological Aspects of the Tumor Microenvironment and Epithelial-Mesenchymal Transition in Gastric Carcinogenesis

2020 ◽  
Vol 21 (7) ◽  
pp. 2544 ◽  
Author(s):  
Jacek Baj ◽  
Karolina Brzozowska ◽  
Alicja Forma ◽  
Amr Maani ◽  
Elżbieta Sitarz ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Host Cell ◽  
Signaling Pathways ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Gastric Carcinogenesis ◽  
World Health ◽  
Mesenchymal Transition ◽  
Methylation Of Dna ◽  
H Pylori

Infection with Helicobacter pylori, a Gram-negative, microaerophilic pathogen often results in gastric cancer in a subset of affected individuals. This explains why H. pylori is the only bacterium classified as a class I carcinogen by the World Health Organization. Several studies have pinpointed mechanisms by which H. pylori alters signaling pathways in the host cell to cause diseases. In this article, the authors have reviewed 234 studies conducted over a span of 18 years (2002–2020). The studies investigated the various mechanisms associated with gastric cancer induction. For the past 1.5 years, researchers have discovered new mechanisms contributing to gastric cancer linked to H. pylori etiology. Alongside alteration of the host signaling pathways using oncogenic CagA pathways, H. pylori induce DNA damage in the host and alter the methylation of DNA as a means of perturbing downstream signaling. Also, with H. pylori, several pathways in the host cell are activated, resulting in epithelial-to-mesenchymal transition (EMT), together with the induction of cell proliferation and survival. Studies have shown that H. pylori enhances gastric carcinogenesis via a multifactorial approach. What is intriguing is that most of the targeted mechanisms and pathways appear common with various forms of cancer.

scholarly journals Characterization of Symbiodinium-associated viruses and implications for coral health

2021 ◽  
Author(s):  
◽  
Scott Anthony Lawrence
Keyword(s):  
Viral Infection ◽  
Host Cell ◽  
Cell Cultures ◽  
Viral Infections ◽  
Lytic Cycle ◽  
Symbiodinium Cell ◽  
Coral Diseases ◽  
Expression Levels ◽  
Virus Like Particles ◽  
Chronic Viral Infections

<p>Coral reefs are in decline worldwide. Much of this decline is attributable to mass coral bleaching events and disease outbreaks, both of which are linked to anthropogenic climate change. Despite increased research effort, much remains unknown about these phenomena, especially the causative agents of many coral diseases. In particular, coral-associated viruses have received little attention, and their potential roles in coral diseases are largely unknown. This study aimed to address this lack of information by characterising the viruses associated with reef-building corals and Symbiodinium (dinoflagellates that can form symbioses with corals).  Symbiodinium virus screening experiments revealed the presence of numerous and varied virus-like particles (VLPs) inside cells. Of the 49 Symbiodinium cultures screened, approximately one third contained putative latent viral infections that could be induced to enter their lytic cycle by UV irradiation. Electron microscope examination revealed VLPs closely resembling viruses previously found in dinoflagellates and other microalgae. Three cultures that showed evidence of latent viral infections were chosen for whole transcriptome sequencing, which revealed the presence of viral genes that were expressed in several different types of Symbiodinium. The relationship between the detected genes and known viral gene sequences suggested that the cells were infected with double-stranded DNA (dsDNA) viruses.  In order to determine how the host cell responds to stress-induced viral infection, the expression levels of genes associated with stress response and viral infection were measured. The expression levels of many genes were unchanged following UV stress, and expression of genes that were predicted to be upregulated following stress, such as those encoding antioxidant enzymes, in fact showed lower expression levels. Despite this, several groups of genes involved in viral infection and host cell response were upregulated following stress, providing further evidence for stress-induced latent or chronic viral infections.  In addition to the research carried out on Symbiodinium cell cultures, viruses associated with three coral diseases were studied using electron microscopy. Virus-like particles were present in coral and Symbiodinium cells from all three diseases, but viral abundance was correlated with disease state in only one: white patch syndrome (WPS) of Porites australiensis. The locations and morphologies of the VLPs associated with WPS suggested the presence of dsDNA and single-stranded RNA (ssRNA) viruses infecting both the coral animal and Symbiodinium cells. DNA sequences obtained from WPS-affected corals matched closely with sequences obtained from VLP-containing Symbiodinium cells. Based on the evidence gathered from Symbiodinium cell cultures and coral tissues, I propose a theoretical model of viral infection in WPS. In this model, the coral animal cells are routinely subject to chronic viral infections, and Symbiodinium cells harbour two types of chronic or latent infections – a dsDNA and an ssRNA virus – that can be induced via stress, resulting in cell lysis or loss of the cells from the coral host.  In addition to detection and rudimentary identification of viruses infecting Symbiodinium cells, this study generated the largest dinoflagellate transcriptomic dataset to date. These data will prove valuable for future research into Symbiodinium, both in terms of viral infections and more generally.</p>

scholarly journals Molecular features similarities between SARS-CoV-2, SARS, MERS and key human genes could favour the viral infections and trigger collateral effects

2020 ◽  
Author(s):  
Lucas L. Maldonado ◽  
Laura Kamenetzky
Keyword(s):  
Viral Infection ◽  
Host Cell ◽  
Viral Infections ◽  
Human Genetics ◽  
High Rate ◽  
Genetic Population ◽  
Molecular Features ◽  
Human Genes ◽  
Viral Genes ◽  
Collateral Effects

AbstractIn December 2019 rising pneumonia cases caused by a novel β-coronavirus (SARS-CoV-2) occurred in Wuhan, China, which has rapidly spread worldwide causing thousands of deaths. The WHO declared the SARS-CoV-2 outbreak as a public health emergency of international concern therefore several scientists are dedicated to the study of the new virus. Since human viruses have codon usage biases that match highly expressed proteins in the tissues they infect and depend on host cell machinery for replication and co-evolution, we selected the genes that are highly expressed in the tissue of human lungs to perform computational studies that permit to compare their molecular features with SARS, SARS-CoV-2 and MERS genes. In our studies, we analysed 91 molecular features for 339 viral genes and 463 human genes that consisted of 677873 codon positions. Hereby, we found that A/T bias in viral genes could propitiate the viral infection favoured by a host dependant specialization using the host cell machinery of only some genes. The envelope protein E, the membrane glycoprotein M and ORF7 could have been further benefited by a high rate of A/T in the third codon position. Thereby, the mistranslation or de-regulation of protein synthesis could produce collateral effects, as a consequence of viral occupancy of the host translation machinery due tomolecular similarities with viral genes. Furthermore, we provided a list of candidate human genes whose molecular features match those of SARS-CoV-2, SARSand MERS genes, which should be considered to be incorporated into genetic population studies to evaluate thesusceptibility to respiratory viral infections caused by these viruses. The results presented here, settle the basis for further research in the field of human genetics associated with the new viral infection, COVID-19, caused by SARS-CoV-2 and for the development of antiviral preventive methods.

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