scholarly journals Epigenetic Regulation Mechanisms in Viral Infections: A Special Focus on COVID-19

2021 ◽  
Author(s):  
Burcu Biterge Süt
Keyword(s):  
Host Cell ◽  
Epigenetic Regulation ◽  
Viral Entry ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Health Concern ◽  
Special Focus ◽  
Comprehensive Overview ◽  
Regulation Mechanisms ◽  
Host Metabolism

The outbreak of Coronavirus Disease-2019 (Covid-19), caused by a novel and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2), is a persisting global health concern. Research so far has successfully identified the molecular mechanisms of viral entry, alterations within the host cell upon infection, and the stimulation of an immune response to fight it. One of the most important cellular regulatory machineries within the host cell to be affected by the SARS-CoV-2 infection is epigenetic regulation, which modulates transcriptional activity by DNA sequence-independent factors such as DNA-methylation, RNA interference and histone modifications. Several studies in the literature have previously reported epigenetic alterations within the host due to infections of the Coronaviridae family viruses including SARS-CoV and MERS-CoV that antagonized immune system activation. Recent studies have also identified epigenetic dysregulation of host metabolism by SARS-CoV-2 infection, linking epigenetic mechanisms with the pathophysiology and illness severity of Covid-19. Therefore, this book chapter aims to provide a comprehensive overview of the epigenetic regulation mechanisms in viral infections with a special focus on SARS-CoV-2 infection.

scholarly journals Significance of thiol-disulfide balance in SARS-CoV-2 infection

2021 ◽  
Vol 72 (3) ◽  
pp. 30-36
Author(s):  
Tatjana Simić
Keyword(s):  
Cell Surface ◽  
Host Cell ◽  
Protein Interactions ◽  
Viral Entry ◽  
Molecular Mechanisms ◽  
Alkylating Agents ◽  
Protein S ◽  
Protein Protein Interactions ◽  
Virus Surface ◽  
Host Cell Surface

Studies of the molecular mechanisms regarding interaction of different viruses with receptors on the host cell surface have shown that the viral entry depends on the specific relationship between free thiol (SH) groups and disulfides on the virus surface, as well as the thiol disulfide balance on the host cell surface. The presence of oxidizing compounds or alkylating agents, which disturb the thiol-disulfide balance on the surface of the virus, can also affect its infectious potential. Disturbed thiol-disulfide balance may also influence protein-protein interactions between SARS-CoV-2 protein S and ACE2 receptors of the host cell. This review presents the basic mechanisms of maintaining intracellular and extracellular thiol disulfide balance and previous experimental and clinical evidence in favor of impaired balance in SARS-CoV-2 infection. Besides, the results of the clinical application or experimental analysis of compounds that induce changes in the thiol disulfide balance towards reduction of disulfide bridges in proteins of interest in COVID-19 infection are presented.

scholarly journals Viral Infection of Human Natural Killer Cells

Viruses ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 243 ◽  
Author(s):  
Elisabeth van Erp ◽  
Mirjam van Kampen ◽  
Puck van Kasteren ◽  
Jelle de Wit
Keyword(s):  
Viral Infection ◽  
Nk Cells ◽  
Natural Killer ◽  
Viral Entry ◽  
Viral Infections ◽  
Nk Cell ◽  
Cell Infection ◽  
Comprehensive Overview ◽  
Human Natural Killer Cells ◽  
Syncytial Virus

Natural killer (NK) cells are essential in the early immune response against viral infections, in particular through clearance of virus-infected cells. In return, viruses have evolved multiple mechanisms to evade NK cell-mediated viral clearance. Several unrelated viruses, including influenza virus, respiratory syncytial virus, and human immunodeficiency virus, can directly interfere with NK cell functioning through infection of these cells. Viral infection can lead to immune suppression, either by downregulation of the cytotoxic function or by triggering apoptosis, leading to depletion of NK cells. In contrast, some viruses induce proliferation or changes in the morphology of NK cells. In this review article, we provide a comprehensive overview of the viruses that have been reported to infect NK cells, we discuss their mechanisms of entry, and describe the interference with NK cell effector function and phenotype. Finally, we discuss the contribution of virus-infected NK cells to viral load. The development of specific therapeutics, such as viral entry inhibitors, could benefit from an enhanced understanding of viral infection of NK cells, opening up possibilities for the prevention of NK cell infection.

scholarly journals Oxysterols in the Immune Response to Bacterial and Viral Infections

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 201
Author(s):  
Cheng Xiang Foo ◽  
Stacey Bartlett ◽  
Katharina Ronacher
Keyword(s):  
Immune Response ◽  
Host Cell ◽  
Bacterial Growth ◽  
Viral Entry ◽  
Drug Targets ◽  
Viral Infections ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Lipid Mediators ◽  
Cholesterol Homeostasis

Oxidized cholesterols, the so-called oxysterols, are widely known to regulate cholesterol homeostasis. However, more recently oxysterols have emerged as important lipid mediators in the response to both bacterial and viral infections. This review summarizes our current knowledge of selected oxysterols and their receptors in the control of intracellular bacterial growth as well as viral entry into the host cell and viral replication. Lastly, we briefly discuss the potential of oxysterols and their receptors as drug targets for infectious and inflammatory diseases.

scholarly journals Evolutionary conflicts and adverse effects of antiviral factors

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Daniel Sauter ◽  
Frank Kirchhoff
Keyword(s):  
Cell Death ◽  
Adverse Effects ◽  
Antiviral Activity ◽  
Host Cell ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Restriction Factors ◽  
Viral Pathogens ◽  
Trade Off ◽  
Viral Spread

Human cells are equipped with a plethora of antiviral proteins protecting them against invading viral pathogens. In contrast to apoptotic or pyroptotic cell death, which serves as ultima ratio to combat viral infections, these cell-intrinsic restriction factors may prevent or at least slow down viral spread while allowing the host cell to survive. Nevertheless, their antiviral activity may also have detrimental effects on the host. While the molecular mechanisms underlying the antiviral activity of restriction factors are frequently well investigated, potential undesired effects of their antiviral functions on the host cell are hardly explored. With a focus on antiretroviral proteins, we summarize in this review how individual restriction factors may exert adverse effects as trade-off for efficient defense against attacking pathogens.

scholarly journals Lassa Virus Cell Entry Reveals New Aspects of Virus-Host Cell Interaction

2016 ◽  
Vol 91 (4) ◽  
Author(s):  
Giulia Torriani ◽  
Clara Galan-Navarro ◽  
Stefan Kunz
Keyword(s):  
Host Cell ◽  
Viral Entry ◽  
Molecular Mechanisms ◽  
Cell Interaction ◽  
Cell Entry ◽  
Lassa Virus ◽  
Human Pathogen ◽  
Highly Pathogenic ◽  
Receptor Recognition ◽  
Host Cell Interaction

ABSTRACT Viral entry represents the first step of every viral infection and is a determinant for the host range and disease potential of a virus. Here, we review the latest developments on cell entry of the highly pathogenic Old World arenavirus Lassa virus, providing novel insights into the complex virus-host cell interaction of this important human pathogen. We will cover new discoveries on the molecular mechanisms of receptor recognition, endocytosis, and the use of late endosomal entry factors.

scholarly journals TNF Decoy Receptors Encoded by Poxviruses

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1065
Author(s):  
Francisco Javier Alvarez-de Miranda ◽  
Isabel Alonso-Sánchez ◽  
Antonio Alcamí ◽  
Bruno Hernaez
Keyword(s):  
Host Response ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Special Focus ◽  
Soluble Receptors ◽  
Decoy Receptors ◽  
Therapeutic Molecules ◽  
Virus Spreading ◽  
Potential Use ◽  
Necrosis Factor

Tumour necrosis factor (TNF) is an inflammatory cytokine produced in response to viral infections that promotes the recruitment and activation of leukocytes to sites of infection. This TNF-based host response is essential to limit virus spreading, thus poxviruses have evolutionarily adopted diverse molecular mechanisms to counteract TNF antiviral action. These include the expression of poxvirus-encoded soluble receptors or proteins able to bind and neutralize TNF and other members of the TNF ligand superfamily, acting as decoy receptors. This article reviews in detail the various TNF decoy receptors identified to date in the genomes from different poxvirus species, with a special focus on their impact on poxvirus pathogenesis and their potential use as therapeutic molecules.

scholarly journals Innate immunology in COVID-19—a living review. Part I: viral entry, sensing and evasion

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Clarissa Coveney ◽  
Michel Tellier ◽  
Fangfang Lu ◽  
Shayda Maleki-Toyserkani ◽  
Ruth Jones ◽  
...  
Keyword(s):  
Immune Evasion ◽  
Viral Entry ◽  
Molecular Mechanisms ◽  
Severe Disease ◽  
World Health ◽  
Health Concern ◽  
Viral Immunity ◽  
Restriction Factors ◽  
Innate Immunology ◽  
Host Restriction

Abstract The coronavirus infectious disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a world health concern and can cause severe disease and high mortality in susceptible groups. While vaccines offer a chance to treat disease, prophylactic and anti-viral treatments are still of vital importance, especially in context of the mutative ability of this group of viruses. Therefore, it is essential to elucidate the molecular mechanisms of viral entry, innate sensing and immune evasion of SARS-CoV-2, which control the triggers of the subsequent excessive inflammatory response. Viral evasion strategies directly target anti-viral immunity, counteracting host restriction factors and hijacking signalling pathways to interfere with interferon production. In Part I of this review, we examine SARS-CoV-2 viral entry and the described immune evasion mechanisms to provide a perspective on how the failure in initial viral sensing by infected cells can lead to immune dysregulation causing fatal COVID-19, discussed in Part II.

scholarly journals Transcriptome and Coronavirus: New Hope and Therapy

2020 ◽  
Vol 11 (2) ◽  
pp. 9541-9552
Keyword(s):  
Viral Infection ◽  
Host Cell ◽  
Genome Size ◽  
Viral Entry ◽  
Viral Infections ◽  
Cell Transformation ◽  
In Vitro Study ◽  
Cell Protein ◽  
Transformation Mechanism

Transcriptome refers to all RNA particles occur inside one cell or inside numerous cells in one organ. Coronaviruses are a family of correlated viruses that induce viral infection. In humans, coronaviruses induce respiratory viral infections that may be mild or dangerous. The coronavirus shape is large circular elements that have round tip outbreaks - the virus diameter particles=120 nm. The RNA viral genome occurs in coronavirus. The coronavirus genome size = 27-34 kilobases, and this size is the largest RNA genome size. The Life cycle of coronavirus includes viral entry, replication, and release. Coronavirus transmission was done through the connection of its protein with host cell receptors in a specific process. There are 4 types of coronavirus genus: (1) Alphacoronavirus, (2) Betacoronavirus, (3) Gammacoronavirus, and (4) Deltacoronavirus. Viral replication, immune evasion, and virion biogenesis correlated with host cell transformation mechanism. Viral molecular mechanism hijacks the host cell protein production mechanism. There is an important host factor (CPSF6) that connects with nuclear protein (NP1). The CPSF6 increases the nuclear production of NP1 in the same time, CPSF6 possesses an important role in the progress of capsid mRNAs inside the nucleus. In a viral infection, there is an increase in mRNA, myeloid differentiation 2-related lipid recognition protein (ML), and Niemann Pick-type C1 (NPC1) genes. Coronavirus is capable of replicating in in vitro study and causes lower transcriptomic variations before 12 h after viral infection. As infection progress, coronavirus causes a significant dysregulation of the host transcriptome greater than the SARS virus. In conclusion, future transcriptome studies are the basis for detecting coronavirus in the human host and for developing a specific preventive and therapeutic method for the virus.

scholarly journals Molecular interactions of TYLCV capsid protein during assembly of viral particles

2007 ◽  
Author(s):  
Yedidya Gafni ◽  
Vitaly Citovsky
Keyword(s):  
Host Cell ◽  
Capsid Protein ◽  
Molecular Interactions ◽  
Viral Entry ◽  
Molecular Mechanisms ◽  
High Specificity ◽  
Single Amino Acid ◽  
Research Findings ◽  
Specific Proteins ◽  
Nuclear Shuttling

Tomato yellow leaf curl geminivirus (TYLCV) is a major pathogen of cultivated tomato, causing up to 100% crop loss in many parts of the world. The present proposal, a continuation of a BARD-funded project, expanded our understanding of the molecular mechanisms by which CP molecules, as well as its pre-coat partner V2, interact with each other (CP), with the viral genome, and with cellular proteins during assembly and movement of the infectious virions. Specifically, two major objectives were proposed: I. To study in detail the molecular interactions between CP molecules and between CP and ssDNA leading to assembly of infectious TYLCV virions. II. To study the roles of host cell factors in TYLCV assembly. Our research toward these goals has produced the following major achievements: • Characterization of the CP nuclear shuttling interactor, karyopherin alpha 1, its pattern of expression and the putative involvement of auxin in regulation of its expression. (#1 in our list of publication, Mizrachy, Dabush et al. 2004). • Identify a single amino acid in the capsid protein’s sequence that is critical for normal virus life-cycle. (#2 in our list of publications, Yaakov, Levy et al. in preparation). • Development of monoclonal antibodies with high specificity to the capsid protein of TYLCV. (#3 in our list of publications, Solmensky, Zrachya et al. in press). • Generation of Tomato plants resistant to TYLCV by expressing transgene coding for siRNA targeted at the TYLCV CP. (#4 in our list of publications, Zrachya, Kumar et al. in press). •These research findings provided significant insights into (i) the molecular interactions of TYLCV capsid protein with the host cell nuclear shuttling receptor, and (ii) the mechanism by which TYLCV V2 is involved in the silencing of PTGS and contributes to the virus pathogenicity effect. Furthermore, the obtained knowledge helped us to develop specific strategies to attenuate TYLCV infection, for example, by blocking viral entry into and/or exit out of the host cell nucleus via siRNA as we showed in our publication recently (# 4 in our list of publications). Finally, in addition to the study of TYLCV nuclear import and export, our research contributed to our understanding of general mechanisms for nucleocytoplasmic shuttling of proteins and nucleic acids in plant cells. Also integration for stable transformation of ssDNA mediated by our model pathogen Agrobacterium tumefaciens led to identification of plant specific proteins involved. 

E6 and E7 oncoproteins: Potential targets of cervical cancer

2020 ◽  
Vol 27 ◽  
Author(s):  
Ramarao Malla ◽  
Mohammad Amjad Kamal
Keyword(s):  
Cervical Cancer ◽  
Drug Resistance ◽  
Host Cell ◽  
Molecular Mechanisms ◽  
Immune Therapy ◽  
Cervical Lesions ◽  
Diagnostic Strategies ◽  
E6 And E7 Oncoproteins ◽  
E6 And E7

: Cervical cancer (CC) is the fourth leading cancer in women in the age group 15-44 globally. Experimental as well as epidemiological studies identified that type16 and 18 HPV cause 70% of precancerous cervical lesions as well as cervical cancer worldwide by bringing about genetic as well as epigenetic changes in the host genome. The insertion of the HPV genome triggers various defense mechanisms including the silencing of tumor suppressor genes as well as activation of oncogenes associated with cancer metastatic pathway. E6 and E7 are small oncoproteins consisting of 150 and 100 amino acids respectively. These oncoproteins affect the regulation of the host cell cycle by interfering with p53 and pRb. Further these oncoproteins adversely affect the normal functions of the host cell by binding to their signaling proteins. Recent studies demonstrated that E6 and E7 oncoproteins are potential targets for CC. Therefore, this review discusses the role of E6 and E7 oncoproteins in metastasis and drug resistance as well as their regulation, early oncogene mediated signaling pathways. This review also uncovers the recent updates on molecular mechanisms of E6 and E7 mediated phytotherapy, gene therapy, immune therapy, and vaccine strategies as well as diagnosis through precision testing. Therefore, understanding the potential role of E6/E7 in metastasis and drug resistance along with targeted treatment, vaccine, and precision diagnostic strategies could be useful for the prevention and treatment of cervical cancer.

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