scholarly journals Apoptosis: Molecular Mechanisms, Regulation and Role in Pathogenesis

1997 ◽  
Vol 8 (2) ◽  
pp. 103-109 ◽  
Author(s):  
Ryan Wei Yan Hung ◽  
Anthony W Chow
Keyword(s):  
Infectious Diseases ◽  
Molecular Mechanisms ◽  
Biochemical Characterization ◽  
Viral Infections ◽  
Data Extraction ◽  
Relevant Information ◽  
Host Cells ◽  
Novel Treatments ◽  
University Of British Columbia ◽  
Cell Death Pathway

OBJECTIVE: To review the current state of knowledge of apoptosis, with an emphasis on identifying potential and established roles for apoptosis in the pathogenesis of infectious diseases.DATA SOURCES: MEDLINE and the University of British Columbia library system were searched using the search subject, “apoptosis”, for the years 1992 to 1996. Further search terms (eg, “pathogenesis”) were used to narrow the results. These review articles and reference books were used as the basis for locating original articles on particular studies.DATA SELECTION: Approximately 40 studies were reviewed, with the criterion for selection being the relevance to either the molecular mechanisms behind apoptosis or roles for apoptosis in the pathogenesis of infectious diseases.DATA EXTRACTION: Relevant information from each study was collated into categories specific to morphological and biochemical characterization, and the regulation and molecular mechanisms of apoptosis and its role in the pathogenesis of infectious diseases.DATA SYNTHESIS AND CONCLUSIONS: Apoptosis is characterized by distinct morphological and biochemical changes that distinguish it from cell necrosis. Different signal transduction events and transcription factors can promote or inhibit apoptosis, although where and how these tie into the cell death pathway is still poorly understood. Apoptosis has been implicated in the pathogenesis of infectious diseases in two distinct ways: first, multicellular organisms use apoptosis to combat viral infections; and second, pathogens can alter the normal process of apoptosis in host cells by abnormal upregulation or downregulation. Many diseases have been shown to implicate apoptosis in their pathogenesis, raising the possibility of novel treatments for some disorders by therapeutically altering the occurrence and course of apoptosis. Therefore, further study of apoptosis in both health and disease needs to be rigorously pursued.

scholarly journals Molecular mechanisms of human herpes viruses inferring with host immune surveillance

2020 ◽  
Vol 8 (2) ◽  
pp. e000841
Author(s):  
Simon Jasinski-Bergner ◽  
Ofer Mandelboim ◽  
Barbara Seliger
Keyword(s):  
Immune Evasion ◽  
Antigen Processing ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Immune Surveillance ◽  
Host Cells ◽  
Herpes Viruses ◽  
Molecular Processes ◽  
Human Herpes ◽  
Human Herpes Viruses

Several human herpes viruses (HHVs) exert oncogenic potential leading to malignant transformation of infected cells and/or tissues. The molecular processes induced by viral-encoded molecules including microRNAs, peptides, and proteins contributing to immune evasion of the infected host cells are equal to the molecular processes of immune evasion mediated by tumor cells independently of viral infections. Such major immune evasion strategies include (1) the downregulation of proinflammatory cytokines/chemokines as well as the induction of anti-inflammatory cytokines/chemokines, (2) the downregulation of major histocompatibility complex (MHC) class Ia directly as well as indirectly by downregulation of the components involved in the antigen processing, and (3) the downregulation of stress-induced ligands for activating receptors on immune effector cells with NKG2D leading the way. Furthermore, (4) immune modulatory molecules like MHC class Ib molecules and programmed cell death1 ligand 1 can be upregulated on infections with certain herpes viruses. This review article focuses on the known molecular mechanisms of HHVs modulating the above-mentioned possibilities for immune surveillance and even postulates a temporal order linking regular tumor immunology with basic virology and offering putatively novel insights for targeting HHVs.

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.

Anti-infective Agents

2021 ◽  
Vol 27 (38) ◽  
pp. 3947-3948
Author(s):  
Haruaki Tomioka
Keyword(s):  
Infectious Diseases ◽  
Viral Infections ◽  
Drug Repositioning ◽  
Three Dimensional ◽  
The Body ◽  
New Drugs ◽  
Host Cells ◽  
Adjunctive Treatment ◽  
Qsar Analysis ◽  
Clinical Control

Certain bacterial, protozoal, and viral infections remain the most frequent infectious diseases causing morbidity and death globally. However, the development of new drugs for the treatment of such infectious diseases has been slow, although some promising drugs have been developed and used for clinical control of such intractable infections. For example, antiviral drugs, including remdesivir and favipiravir, are currently used for the clinical treatment of coronavirus disease 2019 (COVID-19) patients. Notably, these drugs have been developed based on the drug repositioning technique. In addition, some immune-regulatory drugs, including corticosteroids, baricitinib and tocilizumab, help reduce inflammation in the body since inflammation can lead to some of the more severe symptoms of COVID-19 patients. However, at present, we have substantially no new drugs, which act on metabolic reactions by specifically inhibiting viral proteins of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in host cells. Only recombinant antibodies specific to spike proteins of the coronavirus, such as bamlanivimab, etesevimab, casirivimab, and imdevimab, have been approved or are in the development for clinical use as immune-adjunctive treatment of COVID-19 patients with mild symptoms. In this context, the drug design based on quantitative structureactivity relationship (QSAR) analysis, especially three-dimensional-QSAR, may be very beneficial for the development of SARS-CoV-2- specific chemotherapeutic anti-infective agents [1]. ...

scholarly journals Innate Immune Response to Tick-Borne Pathogens: Cellular and Molecular Mechanisms Induced in the Hosts

2020 ◽  
Vol 21 (15) ◽  
pp. 5437 ◽  
Author(s):  
Alessandra Torina ◽  
Sara Villari ◽  
Valeria Blanda ◽  
Stefano Vullo ◽  
Marco Pio La Manna ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Infectious Diseases ◽  
Innate Immune Response ◽  
Molecular Mechanisms ◽  
Defense Mechanism ◽  
Innate Immune ◽  
Bioactive Molecules ◽  
Host Cells ◽  
Ongoing Research

Many pathogens are transmitted by tick bites, including Anaplasma spp., Ehrlichia spp., Rickettsia spp., Babesia and Theileria sensu stricto species. These pathogens cause infectious diseases both in animals and humans. Different types of immune effector mechanisms could be induced in hosts by these microorganisms, triggered either directly by pathogen-derived antigens or indirectly by molecules released by host cells binding to these antigens. The components of innate immunity, such as natural killer cells, complement proteins, macrophages, dendritic cells and tumor necrosis factor alpha, cause a rapid and intense protection for the acute phase of infectious diseases. Moreover, the onset of a pro-inflammatory state occurs upon the activation of the inflammasome, a protein scaffold with a key-role in host defense mechanism, regulating the action of caspase-1 and the maturation of interleukin-1β and IL-18 into bioactive molecules. During the infection caused by different microbial agents, very similar profiles of the human innate immune response are observed including secretion of IL-1α, IL-8, and IFN-α, and suppression of superoxide dismutase, IL-1Ra and IL-17A release. Innate immunity is activated immediately after the infection and inflammasome-mediated changes in the pro-inflammatory cytokines at systemic and intracellular levels can be detected as early as on days 2–5 after tick bite. The ongoing research field of “inflammasome biology” focuses on the interactions among molecules and cells of innate immune response that could be responsible for triggering a protective adaptive immunity. The knowledge of the innate immunity mechanisms, as well as the new targets of investigation arising by bioinformatics analysis, could lead to the development of new methods of emergency diagnosis and prevention of tick-borne infections.

scholarly journals Autocrine and paracrine interferon signaling as 'ring vaccination' and 'contact tracing' strategies to suppress virus infection in a host

2020 ◽  
Author(s):  
G. Michael Lavigne ◽  
Hayley Russell ◽  
Barbara Sherry ◽  
Ruian Ke
Keyword(s):  
Molecular Mechanisms ◽  
Viral Infections ◽  
Population Level ◽  
Host Cells ◽  
Contact Tracing ◽  
Interferon Response ◽  
Paracrine Signaling ◽  
Viral Spread ◽  
Ring Vaccination ◽  
Spread Of Infection

The innate immune response, particularly the interferon response, represents a first line of defense against viral infections. The interferon molecules produced from infected cells act through autocrine and paracrine signaling to turn host cells into an antiviral state. Although the molecular mechanisms of IFN signaling have been well characterized, how the interferon response collectively contribute to the regulation of host cells to stop or suppress viral infection during early infection remain unclear. Here, we use mathematical models to delineate the roles of the autocrine and the paracrine signaling, and show that their impacts on viral spread are dependent on how infection proceeds. In particular, we found that when infection is well-mixed, the paracrine signaling is not as effective; in contrast, when infection spreads in a spatial manner, a likely scenario during initial infection in tissue, the paracrine signaling can impede the spread of infection by decreasing the number of susceptible cells close to the site of infection. Furthermore, we argue that the interferon response can be seen as a parallel to population-level epidemic prevention strategies such as contact tracing or ring vaccination. Thus, our results here may have implications for the outbreak control at the population scale more broadly.

scholarly journals Complexities of Type I Interferon Biology: Lessons from LCMV

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 172 ◽  
Author(s):  
Tamara Suprunenko ◽  
Markus Hofer
Keyword(s):  
Molecular Mechanisms ◽  
Viral Infections ◽  
Type I Interferon ◽  
Malignant Tumors ◽  
Antiviral Immunity ◽  
Lymphocytic Choriomeningitis ◽  
Type I Interferons ◽  
Host Responses ◽  
Type I ◽  
Novel Treatments

Over the past decades, infection of mice with lymphocytic choriomeningitis virus (LCMV) has provided an invaluable insight into our understanding of immune responses to viruses. In particular, this model has clarified the central roles that type I interferons play in initiating and regulating host responses. The use of different strains of LCMV and routes of infection has allowed us to understand how type I interferons are critical in controlling virus replication and fostering effective antiviral immunity, but also how they promote virus persistence and functional exhaustion of the immune response. Accordingly, these discoveries have formed the foundation for the development of novel treatments for acute and chronic viral infections and even extend into the management of malignant tumors. Here we review the fundamental insights into type I interferon biology gained using LCMV as a model and how the diversity of LCMV strains, dose, and route of administration have been used to dissect the molecular mechanisms underpinning acute versus persistent infection. We also identify gaps in the knowledge regarding LCMV regulation of antiviral immunity. Due to its unique properties, LCMV will continue to remain a vital part of the immunologists’ toolbox.

scholarly journals Autocrine and paracrine interferon signalling as ‘ring vaccination’ and ‘contact tracing’ strategies to suppress virus infection in a host

2021 ◽  
Vol 288 (1945) ◽  
pp. 20203002
Author(s):  
G. Michael Lavigne ◽  
Hayley Russell ◽  
Barbara Sherry ◽  
Ruian Ke
Keyword(s):  
Molecular Mechanisms ◽  
Viral Infections ◽  
Population Level ◽  
Host Cells ◽  
Contact Tracing ◽  
Interferon Response ◽  
Paracrine Signalling ◽  
Viral Spread ◽  
Ring Vaccination ◽  
Spread Of Infection

The innate immune response, particularly the interferon response, represents a first line of defence against viral infections. The interferon molecules produced from infected cells act through autocrine and paracrine signalling to turn host cells into an antiviral state. Although the molecular mechanisms of IFN signalling have been well characterized, how the interferon response collectively contribute to the regulation of host cells to stop or suppress viral infection during early infection remain unclear. Here, we use mathematical models to delineate the roles of the autocrine and the paracrine signalling, and show that their impacts on viral spread are dependent on how infection proceeds. In particular, we found that when infection is well-mixed, the paracrine signalling is not as effective; by contrast, when infection spreads in a spatial manner, a likely scenario during initial infection in tissue, the paracrine signalling can impede the spread of infection by decreasing the number of susceptible cells close to the site of infection. Furthermore, we argue that the interferon response can be seen as a parallel to population-level epidemic prevention strategies such as ‘contact tracing’ or ‘ring vaccination’. Thus, our results here may have implications for the outbreak control at the population scale more broadly.

scholarly journals Taking the Scenic Route: Polyomaviruses Utilize Multiple Pathways to Reach the Same Destination

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1168
Author(s):  
Colleen L. Mayberry ◽  
Melissa S. Maginnis
Keyword(s):  
Host Range ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Merkel Cell Polyomavirus ◽  
Host Cells ◽  
Merkel Cell ◽  
Virus Family ◽  
Cellular Processes

Members of the Polyomaviridae family differ in their host range, pathogenesis, and disease severity. To date, some of the most studied polyomaviruses include human JC, BK, and Merkel cell polyomavirus and non-human subspecies murine and simian virus 40 (SV40) polyomavirus. Although dichotomies in host range and pathogenesis exist, overlapping features of the infectious cycle illuminate the similarities within this virus family. Of particular interest to human health, JC, BK, and Merkel cell polyomavirus have all been linked to critical, often fatal, illnesses, emphasizing the importance of understanding the underlying viral infections that result in the onset of these diseases. As there are significant overlaps in the capacity of polyomaviruses to cause disease in their respective hosts, recent advancements in characterizing the infectious life cycle of non-human murine and SV40 polyomaviruses are key to understanding diseases caused by their human counterparts. This review focuses on the molecular mechanisms by which different polyomaviruses hijack cellular processes to attach to host cells, internalize, traffic within the cytoplasm, and disassemble within the endoplasmic reticulum (ER), prior to delivery to the nucleus for viral replication. Unraveling the fundamental processes that facilitate polyomavirus infection provides deeper insight into the conserved mechanisms of the infectious process shared within this virus family, while also highlighting critical unique viral features.

scholarly journals Antiviral Strategies Using Natural Source-Derived Sulfated Polysaccharides in the Light of the COVID-19 Pandemic and Major Human Pathogenic Viruses

Viruses ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 35
Author(s):  
Bimalendu Ray ◽  
Imran Ali ◽  
Subrata Jana ◽  
Shuvam Mukherjee ◽  
Saikat Pal ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Viral Infection ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Structural Characteristics ◽  
Antiviral Agents ◽  
Host Cells ◽  
Sulfated Polysaccharides ◽  
Susceptible Host ◽  
Pathogenic Viruses

Only a mere fraction of the huge variety of human pathogenic viruses can be targeted by the currently available spectrum of antiviral drugs. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has highlighted the urgent need for molecules that can be deployed quickly to treat novel, developing or re-emerging viral infections. Sulfated polysaccharides are found on the surfaces of both the susceptible host cells and the majority of human viruses, and thus can play an important role during viral infection. Such polysaccharides widely occurring in natural sources, specifically those converted into sulfated varieties, have already proved to possess a high level and sometimes also broad-spectrum antiviral activity. This antiviral potency can be determined through multifold molecular pathways, which in many cases have low profiles of cytotoxicity. Consequently, several new polysaccharide-derived drugs are currently being investigated in clinical settings. We reviewed the present status of research on sulfated polysaccharide-based antiviral agents, their structural characteristics, structure–activity relationships, and the potential of clinical application. Furthermore, the molecular mechanisms of sulfated polysaccharides involved in viral infection or in antiviral activity, respectively, are discussed, together with a focus on the emerging methodology contributing to polysaccharide-based drug development.

Treatment of ebola and other infectious diseases: melatonin “goes viral”

2020 ◽  
Vol 3 (1) ◽  
pp. 43-57 ◽  
Author(s):  
Russel J Reiter ◽  
Qiang Ma ◽  
Ramaswamy Sharma
Keyword(s):  
Mortality Rate ◽  
Infectious Diseases ◽  
Hemorrhagic Shock ◽  
Safety Profile ◽  
Ebola Virus ◽  
Viral Infections ◽  
Virus Disease ◽  
Attractive Potential ◽  
Potential Treatment

This review summarizes published reports on the utility of melatonin as a treatment for virus-mediated diseases. Of special note are the data related to the role of melatonin in influencing Ebola virus disease. This infection and deadly condition has no effective treatment and the published works documenting the ability of melatonin to attenuate the severity of viral infections generally and Ebola infection specifically are considered. The capacity of melatonin to prevent one of the major complications of an Ebola infection, i.e., the hemorrhagic shock syndrome, which often contributes to the high mortality rate, is noteworthy. Considering the high safety profile of melatonin, the fact that it is easily produced, inexpensive and can be self-administered makes it an attractive potential treatment for Ebola virus pathology.  

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