scholarly journals Exosome Biogenesis and Biological Function in Response to Viral Infections

2018 ◽  
Vol 12 (1) ◽  
pp. 134-148 ◽  
Author(s):  
Brennetta J. Crenshaw ◽  
Linlin Gu ◽  
Brian Sims ◽  
Qiana L. Matthews
Keyword(s):  
Protein Trafficking ◽  
Viral Infections ◽  
Rna Virus ◽  
Cellular Protein ◽  
Molecular Characteristics ◽  
Exosome Biogenesis ◽  
Pathogen Response ◽  
Viral Hijacking ◽  
The Impact

Introduction: Exosomes are extracellular vesicles that originate as intraluminal vesicles during the process of multivescular body formation. Exosomes mediate intercellular transfer of functional proteins, lipids, and RNAs. The investigation into the formation and role of exosomes in viral infections is still being elucidated. Exosomes and several viruses share similar structural and molecular characteristics. Explanation: It has been documented that viral hijacking exploits the exosomal pathway and mimics cellular protein trafficking. Exosomes released from virus-infected cells contain a variety of viral and host cellular factors that are able to modify recipient host cell responses. Recent studies have demonstrated that exosomes are crucial components in the pathogenesis of virus infection. Exosomes also allow the host to produce effective immunity against pathogens by activating antiviral mechanisms and transporting antiviral factors between adjacent cells. Conclusion: Given the ever-growing roles and importance of exosomes in both host and pathogen response, this review will address the impact role of exosome biogenesis and composition after DNA, RNA virus, on Retrovirus infections. This review also will also address how exosomes can be used as therapeutic agents as well as a vaccine vehicles.

scholarly journals The Role of Micronutrients in Support of the Immune Response against Viral Infections

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3198 ◽  
Author(s):  
Francesco Pecora ◽  
Federica Persico ◽  
Alberto Argentiero ◽  
Cosimo Neglia ◽  
Susanna Esposito
Keyword(s):  
Fatty Acids ◽  
Immune Response ◽  
Immune System ◽  
Viral Infections ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Optimal Function ◽  
The Impact

Viral infections are a leading cause of morbidity and mortality worldwide, and the importance of public health practices including handwashing and vaccinations in reducing their spread is well established. Furthermore, it is well known that proper nutrition can help support optimal immune function, reducing the impact of infections. Several vitamins and trace elements play an important role in supporting the cells of the immune system, thus increasing the resistance to infections. Other nutrients, such as omega-3 fatty acids, help sustain optimal function of the immune system. The main aim of this manuscript is to discuss of the potential role of micronutrients supplementation in supporting immunity, particularly against respiratory virus infections. Literature analysis showed that in vitro and observational studies, and clinical trials, highlight the important role of vitamins A, C, and D, omega-3 fatty acids, and zinc in modulating the immune response. Supplementation with vitamins, omega 3 fatty acids and zinc appears to be a safe and low-cost way to support optimal function of the immune system, with the potential to reduce the risk and consequences of infection, including viral respiratory infections. Supplementation should be in addition to a healthy diet and fall within recommended upper safety limits set by scientific expert bodies. Therefore, implementing an optimal nutrition, with micronutrients and omega-3 fatty acids supplementation, might be a cost-effective, underestimated strategy to help reduce the burden of infectious diseases worldwide, including coronavirus disease 2019 (COVID-19).

scholarly journals Silver Nanoparticles as Potential Antiviral Agents

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2034
Author(s):  
Zubair Ahmed Ratan ◽  
Fazla Rabbi Mashrur ◽  
Anisha Parsub Chhoan ◽  
Sadi Md. Shahriar ◽  
Mohammad Faisal Haidere ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Potential Role ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Host Cells ◽  
Characterization Methods ◽  
New Horizons ◽  
Bacteria And Fungi ◽  
The Impact

Since the early 1990s, nanotechnology has led to new horizons in nanomedicine, which encompasses all spheres of science including chemistry, material science, biology, and biotechnology. Emerging viral infections are creating severe hazards to public health worldwide, recently, COVID-19 has caused mass human casualties with significant economic impacts. Interestingly, silver nanoparticles (AgNPs) exhibited the potential to destroy viruses, bacteria, and fungi using various methods. However, developing safe and effective antiviral drugs is challenging, as viruses use host cells for replication. Designing drugs that do not harm host cells while targeting viruses is complicated. In recent years, the impact of AgNPs on viruses has been evaluated. Here, we discuss the potential role of silver nanoparticles as antiviral agents. In this review, we focus on the properties of AgNPs such as their characterization methods, antiviral activity, mechanisms, applications, and toxicity.

scholarly journals BPIFB3 interacts with ARFGAP1 and TMED9 to regulate non-canonical autophagy and RNA virus infection

2020 ◽  
pp. jcs.251835
Author(s):  
Azia S. Evans ◽  
Nicholas J. Lennemann ◽  
Carolyn B. Coyne
Keyword(s):  
Mass Spectrometry ◽  
Mammalian Cells ◽  
Viral Infections ◽  
Rna Viruses ◽  
Rna Virus ◽  
Negative Regulator ◽  
Host Factors ◽  
Important Negative Regulator ◽  
Cellular Components

Autophagy is a degradative cellular pathway that targets cytoplasmic contents and organelles for turnover by the lysosome. Various autophagy pathways play key roles in the clearance of viral infections, and many families of viruses have developed unique methods for avoiding degradation. Some positive stranded RNA viruses, such as enteroviruses and flaviviruses, usurp the autophagic pathway to promote their own replication. We previously identified the endoplasmic reticulum-localized protein BPIFB3 as an important negative regulator of non-canonical autophagy that uniquely impacts the replication of enteroviruses and flaviviruses. Here, we find that many components of the canonical autophagy machinery are not required for BPIFB3 depletion induced autophagy and identify the host factors that facilitate its role in the replication of enteroviruses and flaviviruses. Using proximity-dependent biotinylation (BioID) followed by mass spectrometry, we identify ARFGAP1 and TMED9 as two cellular components that interact with BPIFB3 to regulate autophagy and viral replication. Importantly, our data demonstrate that non-canonical autophagy in mammalian cells can be controlled outside of the traditional pathway regulators and define the role of two proteins in BPIFB3 depletion mediated non-canonical autophagy.

scholarly journals Role of unfolded proteins in lung disease

Thorax ◽  
2020 ◽  
Vol 76 (1) ◽  
pp. 92-99
Author(s):  
Kirsty L Bradley ◽  
Clare A Stokes ◽  
Stefan J Marciniak ◽  
Lisa C Parker ◽  
Alison M Condliffe
Keyword(s):  
Protein Synthesis ◽  
Er Stress ◽  
Respiratory Diseases ◽  
Viral Infections ◽  
Genetic Manipulation ◽  
Experimental Models ◽  
Misfolded Proteins ◽  
Pharmacological Agents ◽  
The Impact

The lungs are exposed to a range of environmental toxins (including cigarette smoke, air pollution, asbestos) and pathogens (bacterial, viral and fungal), and most respiratory diseases are associated with local or systemic hypoxia. All of these adverse factors can trigger endoplasmic reticulum (ER) stress. The ER is a key intracellular site for synthesis of secretory and membrane proteins, regulating their folding, assembly into complexes, transport and degradation. Accumulation of misfolded proteins within the lumen results in ER stress, which activates the unfolded protein response (UPR). Effectors of the UPR temporarily reduce protein synthesis, while enhancing degradation of misfolded proteins and increasing the folding capacity of the ER. If successful, homeostasis is restored and protein synthesis resumes, but if ER stress persists, cell death pathways are activated. ER stress and the resulting UPR occur in a range of pulmonary insults and the outcome plays an important role in many respiratory diseases. The UPR is triggered in the airway of patients with several respiratory diseases and in corresponding experimental models. ER stress has been implicated in the initiation and progression of pulmonary fibrosis, and evidence is accumulating suggesting that ER stress occurs in obstructive lung diseases (particularly in asthma), in pulmonary infections (some viral infections and in the setting of the cystic fibrosis airway) and in lung cancer. While a number of small molecule inhibitors have been used to interrogate the role of the UPR in disease models, many of these tools have complex and off-target effects, hence additional evidence (eg, from genetic manipulation) may be required to support conclusions based on the impact of such pharmacological agents. Aberrant activation of the UPR may be linked to disease pathogenesis and progression, but at present, our understanding of the context-specific and disease-specific mechanisms linking these processes is incomplete. Despite this, the ability of the UPR to defend against ER stress and influence a range of respiratory diseases is becoming increasingly evident, and the UPR is therefore attracting attention as a prospective target for therapeutic intervention strategies.

scholarly journals Contribution of vaccines to our understanding of pneumococcal disease

2011 ◽  
Vol 366 (1579) ◽  
pp. 2790-2798 ◽  
Author(s):  
Keith P. Klugman
Keyword(s):  
Cause Of Death ◽  
Pneumococcal Disease ◽  
Disease Burden ◽  
Viral Infections ◽  
Bacterial Pathogen ◽  
Pneumococcal Serotypes ◽  
Pneumococcal Infections ◽  
The Impact ◽  
Recent Demonstration

Pneumonia is the leading cause of mortality in children in developing countries and is also the leading infectious cause of death in adults. The most important cause of pneumonia is the Gram-positive bacterial pathogen, Streptococcus pneumoniae , also known as the pneumococcus. It has thus become the leading vaccine-preventable cause of death and is a successful and diverse human pathogen. The development of conjugate pneumococcal vaccines has made possible the prevention of pneumococcal disease in infants, but has also elucidated aspects of pneumococcal biology in a number of ways. Use of the vaccine as a probe has increased our understanding of the burden of pneumococcal disease in children globally. Vaccination has also elucidated the clinical spectrum of vaccine-preventable pneumococcal infections; the identification of a biological niche for multiple pneumococcal serotypes in carriage and the differential invasiveness of pneumococcal serotypes; the impact of pneumococcal transmission among children on disease burden in adults; the role of carriage as a precursor to pneumonia; the plasticity of a naturally transformable pathogen to respond to selective pressure through capsular switching and the accumulation of antibiotic-resistance determinants; and the role of pneumococcal infections in hospitalization and mortality associated with respiratory viral infections, including both seasonal and pandemic influenza. Finally, there has been a recent demonstration that pneumococcal pneumonia in children may be an important cause of hospitalization for those with underlying tuberculosis.

scholarly journals Genetic recombination of poliovirus facilitates subversion of host barriers to infection

2018 ◽  
Author(s):  
Ashley Acevedo ◽  
Andrew Woodman ◽  
Jamie J. Arnold ◽  
Ming Te Yeh ◽  
David Evans ◽  
...  
Keyword(s):  
Virus Replication ◽  
Genetic Recombination ◽  
Rna Virus ◽  
Small Population ◽  
Viral Fitness ◽  
Primary Role ◽  
Rna Recombination ◽  
Viral Mutant ◽  
The Impact

AbstractThe contribution of RNA recombination to viral fitness and pathogenesis is poorly defined. Here, we isolate a recombination-deficient, poliovirus variant and find that, while recombination is detrimental to virus replication in tissue culture, recombination is important for pathogenesis in infected animals. Notably, recombination-defective virus exhibits severe attenuation following intravenous inoculation that is associated with a significant reduction in population size during intra-host spread. Because the impact of high mutational loads manifests most strongly at small population sizes, our data suggest that the repair of mutagenized genomes is an essential function of recombination and that this function may drive the long-term maintenance of recombination in viral species despite its associated fitness costs.Significance StatementRNA recombination is a widespread but poorly understood feature of RNA virus replication. For poliovirus, recombination is involved in the emergence of neurovirulent circulating vaccine-derived poliovirus, which has hampered global poliovirus eradication efforts. This emergence illustrates the power of recombination to drive major adaptive change; however, it remains unclear if these adaptive events represent the primary role of recombination in virus survival. Here, we identify a viral mutant with a reduced rate of recombination and find that recombination also plays a central role in the spread of virus within animal hosts. These results highlight a novel approach for improving the safety of live attenuated vaccines and further our understanding of the role of recombination in virus pathogenesis and evolution.

scholarly journals Malignant Ascites in Ovarian Cancer: Cellular, Acellular, and Biophysical Determinants of Molecular Characteristics and Therapy Response

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4318
Author(s):  
Brittany P. Rickard ◽  
Christina Conrad ◽  
Aaron J. Sorrin ◽  
Mustafa Kemal Ruhi ◽  
Jocelyn C. Reader ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Biology ◽  
Metastatic Cancer ◽  
Treatment Options ◽  
Therapy Response ◽  
Therapy Resistance ◽  
Malignant Ascites ◽  
Molecular Characteristics ◽  
The Impact

Ascites refers to the abnormal accumulation of fluid in the peritoneum resulting from an underlying pathology, such as metastatic cancer. Among all cancers, advanced-stage epithelial ovarian cancer is most frequently associated with the production of malignant ascites and is the leading cause of death from gynecologic malignancies. Despite decades of evidence showing that the accumulation of peritoneal fluid portends the poorest outcomes for cancer patients, the role of malignant ascites in promoting metastasis and therapy resistance remains poorly understood. This review summarizes the current understanding of malignant ascites, with a focus on ovarian cancer. The first section provides an overview of heterogeneity in ovarian cancer and the pathophysiology of malignant ascites. Next, analytical methods used to characterize the cellular and acellular components of malignant ascites, as well the role of these components in modulating cell biology, are discussed. The review then provides a perspective on the pressures and forces that tumors are subjected to in the presence of malignant ascites and the impact of physical stress on therapy resistance. Treatment options for malignant ascites, including surgical, pharmacological and photochemical interventions are then discussed to highlight challenges and opportunities at the interface of drug discovery, device development and physical sciences in oncology.

scholarly journals Significantly Low Levels of IgG Antibodies Against Oncogenic Merkel Cell Polyomavirus in Sera From Females Affected by Spontaneous Abortion

2021 ◽  
Vol 12 ◽  
Author(s):  
Chiara Mazziotta ◽  
Giulia Pellielo ◽  
Mauro Tognon ◽  
Fernanda Martini ◽  
John Charles Rotondo
Keyword(s):  
Antibody Response ◽  
Spontaneous Abortion ◽  
Viral Infections ◽  
Merkel Cell Polyomavirus ◽  
Enzyme Linked Immunosorbent Assay ◽  
Merkel Cell ◽  
Igg Antibodies ◽  
Igg Antibody ◽  
The Impact

Merkel cell polyomavirus (MCPyV) is a small DNA tumor virus ubiquitous in humans. MCPyV establishes a clinically asymptomatic lifelong infection in healthy immunocompetent individuals. Viral infections are considered to be risk factors for spontaneous abortion (SA), which is the most common adverse complication of pregnancy. The role of MCPyV in SA remains undetermined. Herein, the impact of MCPyV infection in females affected by SA was investigated. Specifically, an indirect enzyme-linked immunosorbent assay (ELISA) method with two linear synthetic peptides/mimotopes mimicking MCPyV antigens was used to investigate immunoglobulin G (IgG) antibodies against MCPyV in sera from 94 females affected by SA [mean ± standard deviation (SD) age 35 ± (6) years] and from 96 healthy females undergoing voluntary pregnancy interruption [VI, mean (±SD) age 32 ± (7) years]. MCPyV seroprevalence and serological profiles were analyzed. The overall prevalence of serum IgG antibodies against MCPyV was 35.1% (33/94) and 37.5% (36/96) in SA and VI females, respectively (p > 0.05). Notably, serological profile analyses indicated lower optical densities (ODs) in females with SA compared to those undergoing VI (p < 0.05), thus indicating a reduced IgG antibody response in SA females. Circulating IgGs were identified in sera from SA and VI females. Our immunological findings indicate that a relatively reduced fraction of pregnant females carry serum anti-MCPyV IgG antibodies, while SA females presented a more pronounced decrease in IgG antibody response to MCPyV. Although yet to be determined, this immunological decrease might prompt an increase in MCPyV multiplication events in females experiencing abortive events. The role of MCPyV in SA, if present, remains to be determined.

scholarly journals Nutrient-Dependent Changes of Protein Palmitoylation: Impact on Nuclear Enzymes and Regulation of Gene Expression

2018 ◽  
Vol 19 (12) ◽  
pp. 3820 ◽  
Author(s):  
Matteo Spinelli ◽  
Salvatore Fusco ◽  
Claudio Grassi
Keyword(s):  
Gene Expression ◽  
Protein Trafficking ◽  
Regulation Of Gene Expression ◽  
Cysteine Modification ◽  
Post Translational Modifications ◽  
Protein Palmitoylation ◽  
Physiological Phenomenon ◽  
The Impact ◽  
Protein Lipidation

Diet is the main environmental stimulus chronically impinging on the organism throughout the entire life. Nutrients impact cells via a plethora of mechanisms including the regulation of both protein post-translational modifications and gene expression. Palmitoylation is the most-studied protein lipidation, which consists of the attachment of a molecule of palmitic acid to residues of proteins. S-palmitoylation is a reversible cysteine modification finely regulated by palmitoyl-transferases and acyl-thioesterases that is involved in the regulation of protein trafficking and activity. Recently, several studies have demonstrated that diet-dependent molecules such as insulin and fatty acids may affect protein palmitoylation. Here, we examine the role of protein palmitoylation on the regulation of gene expression focusing on the impact of this modification on the activity of chromatin remodeler enzymes, transcription factors, and nuclear proteins. We also discuss how this physiological phenomenon may represent a pivotal mechanism underlying the impact of diet and nutrient-dependent signals on human diseases.

scholarly journals Bacterial Clearance Is Enhanced by α2,3- and α2,6-Sialyllactose via Receptor-Mediated Endocytosis and Phagocytosis

2018 ◽  
Vol 87 (1) ◽  
Author(s):  
Jimin Kim ◽  
Yong-Jae Kim ◽  
Jae Wha Kim
Keyword(s):  
Breast Milk ◽  
Viral Infections ◽  
Human Breast Milk ◽  
Bacterial Clearance ◽  
Content Type ◽  
Receptor Mediated Endocytosis ◽  
Significant Efficacy ◽  
New Perspective ◽  
The Impact

ABSTRACT Sialyllactose (SL) is a representative human milk oligosaccharide (HMO) of human breast milk. The roles of SL in infant brain development and immunity have been reported in previous studies. In this study, we identified the impact of SL on innate immunity. Our results showed that the administration of SL had significant efficacy on bacterial clearance in Pseudomonas aeruginosa K-infected mice. We also examined the role of SL in the human THP-1 macrophage-like cell line. SL effectively promoted receptor-mediated endocytosis and phagocytosis. Furthermore, SL accelerated the recruitment of Rac1 to the cell membrane, leading to the generation of reactive oxygen species for the elimination of phagocytosed bacteria. Our findings provide a new perspective on the role of SL in breast milk and suggest its application as a therapeutic agent to treat bacterial and viral infections.

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