scholarly journals TRIM Proteins and Their Roles in the Influenza Virus Life Cycle

2020 ◽  
Vol 8 (9) ◽  
pp. 1424
Author(s):  
Hye-Ra Lee ◽  
Myoung Kyu Lee ◽  
Chan Woo Kim ◽  
Meehyein Kim
Keyword(s):  
Influenza Virus ◽  
Signaling Pathways ◽  
Viral Infections ◽  
Influenza Virus Infection ◽  
Ubiquitin Proteasome System ◽  
Viral Propagation ◽  
Cellular Processes ◽  
Ubiquitin Proteasome ◽  
Immune Sensing ◽  
Trim Proteins

The ubiquitin-proteasome system (UPS) has been recognized for regulating fundamental cellular processes, followed by induction of proteasomal degradation of target proteins, and triggers multiple signaling pathways that are crucial for numerous aspects of cellular physiology. Especially tripartite motif (TRIM) proteins, well-known E3 ubiquitin ligases, emerge as having critical roles in several antiviral signaling pathways against varying viral infections. Here we highlight recent advances in the study of antiviral roles of TRIM proteins toward influenza virus infection in terms of the modulation of pathogen recognition receptor (PRR)-mediated innate immune sensing, direct obstruction of influenza viral propagation, and participation in virus-induced autophagy.

scholarly journals Proteasome homeostasis is essential for a robust cauliflower mosaic virus infection

2021 ◽  
Author(s):  
Aayushi Shukla ◽  
Suayib Ustun ◽  
Anders Hafrén
Keyword(s):  
Mosaic Virus ◽  
Viral Infections ◽  
Plant Immunity ◽  
Ubiquitin Proteasome System ◽  
Cauliflower Mosaic Virus ◽  
Fine Tuning ◽  
Cellular Processes ◽  
Ubiquitin Proteasome ◽  
Specific Virus ◽  
And Shifts

SummaryThe ubiquitin-proteasome system (UPS) is essential for the maintenance and shifts in protein homeostasis, and thereby forms a founding pillar in virtually all cellular processes including plant immunity and viral infections. According to its importance in fine-tuning the complex plant immune response, proteasomal defects result in divergent outcomes including both resistance and susceptibility phenotypes in response to viruses. The final outcome will largely depend on the specific virus and its specific co-adaptation with the UPS as well as the immune system. Here, we show that cauliflower mosaic virus (CaMV) relies on the proteasome for robust infection. The proteasome system is induced during infection via SA and supports systemic accumulation of the virus as well as plant growth performance during infection. This establishes the UPS as a win-win pathway for the plant and the virus, and together with our demonstration of a proteasome-suppressing viral effector, the intimacy between the proteasome and CaMV is fortified.

scholarly journals A Nut for Every Bolt: Subunit-Selective Inhibitors of the Immunoproteasome and Their Therapeutic Potential

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1929
Author(s):  
Eva M. Huber ◽  
Michael Groll
Keyword(s):  
Cell Cycle Progression ◽  
Therapeutic Potential ◽  
Cell Signalling ◽  
Selective Inhibition ◽  
Ubiquitin Proteasome System ◽  
Cellular Processes ◽  
Chemical Structures ◽  
Phase Ii Clinical Trials ◽  
Ubiquitin Proteasome ◽  
Recent Trends

At the heart of the ubiquitin–proteasome system, the 20S proteasome core particle (CP) breaks down the majority of intracellular proteins tagged for destruction. Thereby, the CP controls many cellular processes including cell cycle progression and cell signalling. Inhibitors of the CP can suppress these essential biological pathways, resulting in cytotoxicity, an effect that is beneficial for the treatment of certain blood cancer patients. During the last decade, several preclinical studies demonstrated that selective inhibition of the immunoproteasome (iCP), one of several CP variants in mammals, suppresses autoimmune diseases without inducing toxic side effects. These promising findings led to the identification of natural and synthetic iCP inhibitors with distinct chemical structures, varying potency and subunit selectivity. This review presents the most prominent iCP inhibitors with respect to possible scientific and medicinal applications, and discloses recent trends towards pan-immunoproteasome reactive inhibitors that cumulated in phase II clinical trials of the lead compound KZR-616 for chronic inflammations.

scholarly journals Inhibition of H1N1 influenza virus by selenium nanoparticles loaded with zanamivir through p38 and JNK signaling pathways

RSC Advances ◽  
2017 ◽  
Vol 7 (56) ◽  
pp. 35290-35296 ◽  
Author(s):  
Zhengfang Lin ◽  
Yinghua Li ◽  
Min Guo ◽  
Misi Xiao ◽  
Changbing Wang ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Signaling Pathways ◽  
Clinical Application ◽  
Influenza Virus Infection ◽  
Aqueous Solubility ◽  
H1n1 Influenza ◽  
Solubility Limit ◽  
H1n1 Influenza Virus ◽  
Jnk Signaling

Zanamivir is an effective drug for influenza virus infection, but strong molecular polarity and aqueous solubility limit its clinical application.

scholarly journals Ubiquitin carboxyl-terminal hydrolases are required for period maintenance of the circadian clock at high temperature in Arabidopsis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ryosuke Hayama ◽  
Peizhen Yang ◽  
Federico Valverde ◽  
Tsuyoshi Mizoguchi ◽  
Ikuyo Furutani-Hayama ◽  
...  
Keyword(s):  
Circadian Clock ◽  
High Temperatures ◽  
Elevated Temperatures ◽  
Control Period ◽  
Ubiquitin Proteasome System ◽  
26S Proteasome ◽  
Cellular Processes ◽  
Control Functions ◽  
Ubiquitin Proteasome ◽  
Carboxyl Terminal

AbstractProtein ubiquitylation participates in a number of essential cellular processes including signal transduction and transcription, often by initiating the degradation of specific substrates through the 26S proteasome. Within the ubiquitin-proteasome system, deubiquitylating enzymes (DUBs) not only help generate and maintain the supply of free ubiquitin monomers, they also directly control functions and activities of specific target proteins by modulating the pool of ubiquitylated species. Ubiquitin carboxyl-terminal hydrolases (UCHs) belong to an enzymatic subclass of DUBs, and are represented by three members in Arabidopsis, UCH1, UCH2 and UCH3. UCH1 and UCH2 influence auxin-dependent developmental pathways in Arabidopsis through their deubiquitylation activities, whereas biological and enzymatic functions of UCH3 remain unclear. Here, we demonstrate that Arabidopsis UCH3 acts to maintain the period of the circadian clock at high temperatures redundantly with UCH1 and UCH2. Whereas single uch1, uch2 and uch3 mutants have weak circadian phenotypes, the triple uch mutant displays a drastic lengthening of period at high temperatures that is more extreme than the uch1 uch2 double mutant. UCH3 also possesses a broad deubiquitylation activity against a range of substrates that link ubiquitin via peptide and isopeptide linkages. While the protein target(s) of UCH1-3 are not yet known, we propose that these DUBs act on one or more factors that control period length of the circadian clock through removal of their bound ubiquitin moieties, thus ensuring that the clock oscillates with a proper period even at elevated temperatures.

scholarly journals Caffeoylquinic Acids Are Major Constituents with Potent Anti-Influenza Effects in Brazilian Green Propolis Water Extract

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Tomohiko Urushisaki ◽  
Tomoaki Takemura ◽  
Shigemi Tazawa ◽  
Mayuko Fukuoka ◽  
Junji Hosokawa-Muto ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Viral Infections ◽  
Influenza Virus Infection ◽  
Water Extract ◽  
H1n1 Influenza ◽  
Caffeoylquinic Acids ◽  
Cytoprotective Activity ◽  
Infected Cells ◽  
Brazilian Green Propolis

Influenza A viral infections reached pandemic levels in 1918, 1957, 1968, and, most recently, in 2009 with the emergence of the swine-origin H1N1 influenza virus. The development of novel therapeutics or prophylactics for influenza virus infection is urgently needed. We examined the evaluation of the anti-influenza virus (A/WSN/33 (H1N1)) activity of Brazilian green propolis water extract (PWE) and its constituents by cell viability and real-time PCR assays. Our findings showed strong evidence that PWE has an anti-influenza effect and demonstrate that caffeoylquinic acids are the active anti-influenza components of PWE. Furthermore, we have found that the amount of viral RNA per cell remained unchanged even in the presence of PWE, suggesting that PWE has no direct impact on the influenza virus but may have a cytoprotective activity by affecting internal cellular process. These findings indicate that caffeoylquinic acids are the active anti-influenza components of PWE. Above findings might facilitate the prophylactic application of natural products and the realization of novel anti-influenza drugs based on caffeoylquinic acids, as well as further the understanding of cytoprotective intracellular mechanisms in influenza virus-infected cells.

The ubiquitin proteasome system in atrophying skeletal muscle: roles and regulation

2016 ◽  
Vol 311 (3) ◽  
pp. C392-C403 ◽  
Author(s):  
Philippe A. Bilodeau ◽  
Erin S. Coyne ◽  
Simon S. Wing
Keyword(s):  
Signaling Pathways ◽  
Muscle Atrophy ◽  
Molecular Mechanisms ◽  
Muscle Wasting ◽  
Clinical Problem ◽  
Ubiquitin Proteasome System ◽  
Mechanisms Of Action ◽  
Loss Of Function ◽  
Critical Determinant ◽  
Ubiquitin Proteasome

Muscle atrophy complicates many diseases as well as aging, and its presence predicts both decreased quality of life and survival. Much work has been conducted to define the molecular mechanisms involved in maintaining protein homeostasis in muscle. To date, the ubiquitin proteasome system (UPS) has been shown to play an important role in mediating muscle wasting. In this review, we have collated the enzymes in the UPS whose roles in muscle wasting have been confirmed through loss-of-function studies. We have integrated information on their mechanisms of action to create a model of how they work together to produce muscle atrophy. These enzymes are involved in promoting myofibrillar disassembly and degradation, activation of autophagy, inhibition of myogenesis as well as in modulating the signaling pathways that control these processes. Many anabolic and catabolic signaling pathways are involved in regulating these UPS genes, but none appear to coordinately regulate a large number of these genes. A number of catabolic signaling pathways appear to instead function by inhibition of the insulin/IGF-I/protein kinase B anabolic pathway. This pathway is a critical determinant of muscle mass, since it can suppress key ubiquitin ligases and autophagy, activate protein synthesis, and promote myogenesis through its downstream mediators such as forkhead box O, mammalian target of rapamycin, and GSK3β, respectively. Although much progress has been made, a more complete inventory of the UPS genes involved in mediating muscle atrophy, their mechanisms of action, and their regulation will be useful for identifying novel therapeutic approaches to this important clinical problem.

scholarly journals The UNC-45 chaperone mediates sarcomere assembly through myosin degradation in Caenorhabditis elegans

2007 ◽  
Vol 177 (2) ◽  
pp. 205-210 ◽  
Author(s):  
Megan L. Landsverk ◽  
Shumin Li ◽  
Alex H. Hutagalung ◽  
Ayaz Najafov ◽  
Thorsten Hoppe ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Proteasome Inhibition ◽  
Thick Filament ◽  
Ubiquitin Proteasome System ◽  
Loss Of Function ◽  
Cellular Processes ◽  
Ubiquitin Proteasome ◽  
Myosin Motors ◽  
And Function ◽  
Sarcomere Assembly

Myosin motors are central to diverse cellular processes in eukaryotes. Homologues of the myosin chaperone UNC-45 have been implicated in the assembly and function of myosin-containing structures in organisms from fungi to humans. In muscle, the assembly of sarcomeric myosin is regulated to produce stable, uniform thick filaments. Loss-of-function mutations in Caenorhabditis elegans UNC-45 lead to decreased muscle myosin accumulation and defective thick filament assembly, resulting in paralyzed animals. We report that transgenic worms overexpressing UNC-45 also display defects in myosin assembly, with decreased myosin content and a mild paralysis phenotype. We find that the reduced myosin accumulation is the result of degradation through the ubiquitin/proteasome system. Partial proteasome inhibition is able to restore myosin protein and worm motility to nearly wild-type levels. These findings suggest a mechanism in which UNC-45–related proteins may contribute to the degradation of myosin in conditions such as heart failure and muscle wasting.

scholarly journals Macrolide Therapy in Respiratory Viral Infections

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Jin-Young Min ◽  
Yong Ju Jang
Keyword(s):  
Influenza Virus ◽  
Viral Infection ◽  
Viral Infections ◽  
Wide Spectrum ◽  
Influenza Virus Infection ◽  
Respiratory Viral Infection ◽  
Rsv Infection ◽  
Respiratory Viral Infections ◽  
Syncytial Virus ◽  
Viral Titers

Background. Macrolides have received considerable attention for their anti-inflammatory and immunomodulatory actions beyond the antibacterial effect. These two properties may ensure some efficacy in a wide spectrum of respiratory viral infections. We aimed to summarize the properties of macrolides and their efficacy in a range of respiratory viral infection.Methods. A search of electronic journal articles through PubMed was performed using combinations of the following keywords including macrolides and respiratory viral infection.Results. Bothin vitroandin vivostudies have provided evidence of their efficacy in respiratory viral infections including rhinovirus (RV), respiratory syncytial virus (RSV), and influenza virus. Much data showed that macrolides reduced viral titers of RV ICAM-1, which is the receptor for RV, and RV infection-induced cytokines including IL-1β, IL-6, IL-8, and TNF-α. Macrolides also reduced the release of proinflammatory cytokines which were induced by RSV infection, viral titers, RNA of RSV replication, and the susceptibility to RSV infection partly through the reduced expression of activated RhoA which is an RSV receptor. Similar effects of macrolides on the influenza virus infection and augmentation of the IL-12 by macrolides which is essential in reducing virus yield were revealed.Conclusion. This paper provides an overview on the properties of macrolides and their efficacy in various respiratory diseases.

Influenza virus infection induces translocation of apoptosis-inducing factor (AIF) in A549 cells: role of AIF in apoptosis and viral propagation

2016 ◽  
Vol 162 (3) ◽  
pp. 669-675 ◽  
Author(s):  
Xinyan Qu ◽  
Xiaoran Ding ◽  
Ming Duan ◽  
Jing Yang ◽  
Ruxian Lin ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
A549 Cells ◽  
Influenza Virus Infection ◽  
Viral Propagation ◽  
Apoptosis Inducing Factor

scholarly journals Autoimmune neutropenia associated with influenza virus infection in childhood: a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ignacio Callejas Caballero ◽  
Marta Illán Ramos ◽  
Arantxa Berzosa Sánchez ◽  
Eduardo Anguita ◽  
José Tomás Ramos Amador
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Viral Infections ◽  
Influenza Infection ◽  
Influenza Virus Infection ◽  
Rapid Test ◽  
Male Infant ◽  
Severe Neutropenia ◽  
Autoimmune Neutropenia ◽  
Benign Condition

Abstract Background Although neutropenia is relatively frequent in infants and children and is mostly a benign condition with a self-limited course, it can lead to life-threatening severe infections. Autoimmune neutropenia is a relatively uncommon hematological disorder characterized by the autoantibody-induced destruction of neutrophils. It is usually triggered by viral infections with very few documented cases after influenza virus. Case presentation An 8-month-old male infant presented at the emergency room with a 5-days history of fever up to 39.7 °C, cough and runny nose. In the blood test performed, severe neutropenia was diagnosed (neutrophils 109/μL). A nasopharyngeal aspirate revealed a positive rapid test for Influenza A. Serum antineutrophil antibodies were determined with positive results. Neutropenia targeted panel showed no mutations. Despite maintenance of severe neutropenia for 9 months the course was uneventful without treatment. Conclusions When severe neutropenia is diagnosed and confirmed, it is essential to rule out some potential etiologies and underlying conditions, since the appropriate subsequent management will depend on it. Although autoimmune neutropenia triggered by viral infections has been widely reported, it has seldom been reported after influenza infection. The benign course of the disease allows a conservative management in most cases.

Sign in / Sign up

Export Citation Format

Share Document