scholarly journals Membrane-Associated Flavivirus Replication Complex—Its Organization and Regulation

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1060
Author(s):  
Eiji Morita ◽  
Youichi Suzuki
Keyword(s):  
Protein Translation ◽  
Immune Defense ◽  
Membranous Structure ◽  
Replication Complex ◽  
Virion Assembly ◽  
Cellular Factors ◽  
Life Threatening ◽  
And Function ◽  
Cellular Immune ◽  
Flavivirus Infection

Flavivirus consists of a large number of arthropod-borne viruses, many of which cause life-threatening diseases in humans. A characteristic feature of flavivirus infection is to induce the rearrangement of intracellular membrane structure in the cytoplasm. This unique membranous structure called replication organelle is considered as a microenvironment that provides factors required for the activity of the flaviviral replication complex. The replication organelle serves as a place to coordinate viral RNA amplification, protein translation, and virion assembly and also to protect the viral replication complex from the cellular immune defense system. In this review, we summarize the current understanding of how the formation and function of membrane-associated flaviviral replication organelle are regulated by cellular factors.

Nonmalignant Disorders of Leukocytes

2011 ◽  
Author(s):  
Alison M. Schram ◽  
Nancy Berliner
Keyword(s):  
Blood Cells ◽  
Langerhans Cell Histiocytosis ◽  
White Blood Cells ◽  
Cell Types ◽  
Immune Defense ◽  
Cancer Surveillance ◽  
Vasoactive Substances ◽  
Clinical Disorders ◽  
Life Threatening ◽  
And Function

Leukocytes, also known as white blood cells, are hematologic cells important for a host’s immune defense. They comprise several diverse cell types including lymphocytes, neutrophils, monocytes, macrophages, and eosinophils. Each plays a unique and important role in fighting infection, cancer surveillance, and maintaining immune homeostasis. Leukocytes exert their effect and interact with host and foreign cells through the release of cytokines, chemokines, enzymes, and vasoactive substances. Altered number and function of these cells can lead to clinical disorders that range from benign to severe and life-threatening. Here we review the diagnosis, natural history, and treatment of nonmalignant disorders of leukocytes. This review contains 100 references, 6 figures, and 9 tables. Key Words: eosinophilia, hemophagocytic histiocytosis, Langerhans cell histiocytosis, lymphocytopenia, lymphocytosis mastocytosis, neutropenia, neutrophilia

scholarly journals Susceptibility Genes to Plant Viruses

Viruses ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 484 ◽  
Author(s):  
Hernan Garcia-Ruiz
Keyword(s):  
Virus Replication ◽  
Defense Responses ◽  
Plant Viruses ◽  
Host Factors ◽  
Replication Proteins ◽  
Replication Complex ◽  
Virion Assembly ◽  
Rna Translation ◽  
Cellular Factors ◽  
Genetically Determined

Plant viruses use cellular factors and resources to replicate and move. Plants respond to viral infection by several mechanisms, including innate immunity, autophagy, and gene silencing, that viruses must evade or suppress. Thus, the establishment of infection is genetically determined by the availability of host factors necessary for virus replication and movement and by the balance between plant defense and viral suppression of defense responses. Host factors may have antiviral or proviral activities. Proviral factors condition susceptibility to viruses by participating in processes essential to the virus. Here, we review current advances in the identification and characterization of host factors that condition susceptibility to plant viruses. Host factors with proviral activity have been identified for all parts of the virus infection cycle: viral RNA translation, viral replication complex formation, accumulation or activity of virus replication proteins, virus movement, and virion assembly. These factors could be targets of gene editing to engineer resistance to plant viruses.

scholarly journals Hepatitis C Viral Replication Complex

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 520
Author(s):  
Hui-Chun Li ◽  
Chee-Hing Yang ◽  
Shih-Yen Lo
Keyword(s):  
Hepatitis C ◽  
Viral Entry ◽  
Rna Structure ◽  
Protein Translation ◽  
Rna Replication ◽  
Genomic Rna ◽  
Replication Complex ◽  
Cis Acting ◽  
Cellular Factors ◽  
Direct Acting

The life cycle of the hepatitis C virus (HCV) can be divided into several stages, including viral entry, protein translation, RNA replication, viral assembly, and release. HCV genomic RNA replication occurs in the replication organelles (RO) and is tightly linked to ER membrane alterations containing replication complexes (proteins NS3 to NS5B). The amplification of HCV genomic RNA could be regulated by the RO biogenesis, the viral RNA structure (i.e., cis-acting replication elements), and both viral and cellular proteins. Studies on HCV replication have led to the development of direct-acting antivirals (DAAs) targeting the replication complex. This review article summarizes the viral and cellular factors involved in regulating HCV genomic RNA replication and the DAAs that inhibit HCV replication.

In Silico Identification of a Potent Arsenic Based Approved Drug Darinaparsin against SARS-CoV-2: Inhibitor of RNA Dependent RNA polymerase (RdRp) and Essential Proteases

2020 ◽  
Vol 20 ◽  
Author(s):  
Trinath Chowdhury ◽  
Gourisankar Roymahapatra ◽  
Santi M. Mandal
Keyword(s):  
Rna Polymerase ◽  
Viral Entry ◽  
In Silico ◽  
Rna Dependent Rna Polymerase ◽  
Replication Complex ◽  
In Silico Study ◽  
Life Threatening ◽  
In Vivo Analysis ◽  
3Cl Protease

Background: COVID-19 is a life threatening novel corona viral infection to our civilization and spreading rapidly. Terrific efforts are generous by the researchers to search for a drug to control SARS-CoV-2. Methods: Here, a series of arsenical derivatives were optimized and analyzed with in silico study to search the inhibitor of RNA dependent RNA polymerase (RdRp), the major replication factor of SARS-CoV-2. All the optimized derivatives were blindly docked with RdRp of SARS-CoV-2 using iGEMDOCK v2.1. Results: Based on the lower idock score in the catalytic pocket of RdRp, darinaparsin (-82.52 kcal/mol) revealed most effective among them. Darinaparsin strongly binds with both Nsp9 replicase protein (-8.77 kcal/mol) and Nsp15 endoribonuclease (-8.3 kcal/mol) of SARS-CoV-2 as confirmed from the AutoDock analysis. During infection, the ssRNA of SARS-CoV2 is translated into large polyproteins forming viral replication complex by specific proteases like 3CL protease and papain protease. This is also another target to control the virus infection where darinaparsin also perform the inhibitory role to proteases of 3CL protease (-7.69 kcal/mol) and papain protease (-8.43 kcal/mol). Conclusion: In host cell, the furin protease serves as a gateway to the viral entry and darinaparsin docked with furin protease which revealed a strong binding affinity. Thus, screening of potential arsenic drugs would help in providing the fast invitro to in-vivo analysis towards development of therapeutics against SARS-CoV-2.

scholarly journals Flavivirus NS1 and Its Potential in Vaccine Development

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 622
Author(s):  
Kassandra L. Carpio ◽  
Alan D. T. Barrett
Keyword(s):  
Vaccine Development ◽  
Virus Assembly ◽  
Ns1 Protein ◽  
Human Pathogens ◽  
Unusual Structure ◽  
Replication Complex ◽  
Virus Challenge ◽  
Humoral Immune ◽  
Tick Borne Encephalitis ◽  
Flavivirus Infection

The Flavivirus genus contains many important human pathogens, including dengue, Japanese encephalitis (JE), tick-borne encephalitis (TBE), West Nile (WN), yellow fever (YF) and Zika (ZIK) viruses. While there are effective vaccines for a few flavivirus diseases (JE, TBE and YF), the majority do not have vaccines, including WN and ZIK. The flavivirus nonstructural 1 (NS1) protein has an unusual structure–function because it is glycosylated and forms different structures to facilitate different roles intracellularly and extracellularly, including roles in the replication complex, assisting in virus assembly, and complement antagonism. It also plays a role in protective immunity through antibody-mediated cellular cytotoxicity, and anti-NS1 antibodies elicit passive protection in animal models against a virus challenge. Historically, NS1 has been used as a diagnostic marker for the flavivirus infection due to its complement fixing properties and specificity. Its role in disease pathogenesis, and the strong humoral immune response resulting from infection, makes NS1 an excellent target for inclusion in candidate flavivirus vaccines.

scholarly journals Platelet Phenotyping and Function Testing in Thrombocytopenia

2021 ◽  
Vol 10 (5) ◽  
pp. 1114
Author(s):  
Kerstin Jurk ◽  
Yavar Shiravand
Keyword(s):  
Function Analysis ◽  
Point Of Care ◽  
Bleeding Complications ◽  
Diagnostic Significance ◽  
Blood Samples ◽  
Skilled Personnel ◽  
Life Threatening ◽  
And Function ◽  
Function Testing

Patients who suffer from inherited or acquired thrombocytopenia can be also affected by platelet function defects, which potentially increase the risk of severe and life-threatening bleeding complications. A plethora of tests and assays for platelet phenotyping and function analysis are available, which are, in part, feasible in clinical practice due to adequate point-of-care qualities. However, most of them are time-consuming, require experienced and skilled personnel for platelet handling and processing, and are therefore well-established only in specialized laboratories. This review summarizes major indications, methods/assays for platelet phenotyping, and in vitro function testing in blood samples with reduced platelet count in relation to their clinical practicability. In addition, the diagnostic significance, difficulties, and challenges of selected tests to evaluate the hemostatic capacity and specific defects of platelets with reduced number are addressed.

The Study on the Clinical Phenotype and Function of HPRT1 Gene

2021 ◽  
Author(s):  
Miao Guo ◽  
Yucai Chen ◽  
Longlong Lin ◽  
Yilin Wang ◽  
Anqi Wang ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Clinical Manifestations ◽  
Protein Translation ◽  
Dimensional Structure ◽  
Normal Individuals ◽  
Second Generation Sequencing ◽  
Self Harm ◽  
And Function ◽  
Neurogenetic Disease ◽  
Generation Sequencing

Abstract Background: Lesch-Nyhan disease (LND) is a rare x-linked purine metabolic neurogenetic disease caused by enzyme hypoxanthine-guanine phosphoriribosyltransferase(HGprt) deficiency, also known as self-destructive appearance syndrome. A series of manifestations are caused by abnormal purine metabolism. The typical clinical manifestations are hyperuricemia, growth retardation, mental retardation, short stature, dance-like athetosis, aggressive behavior, and compulsive self-harm.. Results: we identified a point mutation c.151C > T (p. Arg51*) in a pedigree. We analyzed the clinical characteristics of children in a family, and obtained the blood of their parents and siblings for second-generation sequencing. At the same time, we also analyzed and compared the expression of HPRT1 gene and predicted the three-dimensional structure of the protein. And we analyzed the clinical manifestations caused by the defect of the HPRT1 genethe mutation led to the termination of transcription at the 51st arginine, resulting in the production of truncated protein, and the relative expression of HPRT1 gene in patients was significantly lower than other family members and 10 normal individuals. Conclusion: this mutation leads to the early termination of protein translation and the formation of a truncated HPRT protein, which affects the function of the protein and generates corresponding clinical manifestations.

scholarly journals Liver Tolerance to Repeat 90Y-Microsphere Radioembolization

2008 ◽  
Vol 2 (2) ◽  
Author(s):  
Patrick McNeillie ◽  
Andrew S. Kennedy ◽  
William Dezarn ◽  
Scott L. Sailer ◽  
Mary England ◽  
...  
Keyword(s):  
Liver Function ◽  
Liver Tumors ◽  
Liver Volume ◽  
Dose Calculation ◽  
External Beam Radiation ◽  
Beam Radiation ◽  
Resin Microspheres ◽  
Life Threatening ◽  
Radiation Induced ◽  
And Function

Purpose: Liver tolerance to multiple doses of Y90-microspheres is not known. Many patients (pts) are surviving long enough to be considered for a second and third liver treatments with internal radiation. Materials and Methods: The experience of a single center treating liver tumors with resin Y90-microspheres. Pts that received liver radiation prior to or after resin microsphere therapy were studied. Endpoints were toxicity, tumor response, shunting to lung, and effects on liver volume and function. The delivery activity of microspheres selected was not reduced below BSA dose calculation for patients without prior treatment. All patients received bilobar single session delivery. Results: A total of 38 pts; 14 women, 24 men, treated 6∕2003 to 9∕2006, with 33 pts receiving 2 courses and 5 pts with 3 courses of liver radiation. Retreatment with resin microspheres 26 pts, prior external beam radiation in 7 pts, prior glass microspheres in 2 pts, prior systemic radiotherapy in 2 pts, and prior stereotactic liver radiation in 1 pt. Liver function was stable and adequate in all patients after additional liver radiation, and no pts developed radiation-induced liver dysfunction (RILD) or veno-occlusive disease (VOD). The percentage of shunting to the lung decreased with retreatment. Conclusions: Repeated implantation in the liver with Y90-microspheres is safe in patients that have sufficient liver function and reserve based on known and accepted laboratory parameters already used for selection of microsphere therapy. No acute life-threatening, fatal, or late liver damage was observed, RILD or VOD. No specific dose reduction is recommended for retreatment of the liver.

Abstract 17384: Cardiac-Specific Overexpression of Human Mutant Desmoplakin in Mice Disrupts Cardiac Voltage-Gated Sodium Channel Expression

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Subat Turdi ◽  
Jeffrey A Towbin
Keyword(s):  
Sodium Channel ◽  
Fatty Infiltration ◽  
Electrical Coupling ◽  
Cx43 Expression ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated ◽  
Intercalated Discs ◽  
Channel Expression ◽  
Life Threatening ◽  
And Function

Introduction: Arrhythmogenic cardiomyopathy (AC) is characterized by bi-ventricular dilation, fibro-fatty infiltration and life-threatening arrhythmias. Disruptions in cardiac voltage-gated sodium channel (Nav1.5) expression and function are known to cause arrhythmias. We have demonstrated that cardiac-specific overexpression of human mutant desmoplakin (DSP, Tg-R2834H) in mice leads to AC. However, whether mutant DSP expression in the heart affects the Nav1.5 distribution and function are unknown Hypothesis: Here, we tested whether Nav1.5 localization and expression are altered in the R2834H-Tg mouse hearts. Methods: Primary cardiomyocytes and frozen myocardial sections from non-transgenic (NTg), wild-type DSP (Tg-DSP) and Tg-R2834H mice were used for immunofluorescence studies to assess subcellular localization of DSP, desmin, Nav1.5, Cx43, plakoglobin and β-catenin. Western blot and qPCR were used for quantitative analysis. Results: Double staining of cardiomyocytes from NTg mice with DSP and Nav1.5 revealed that Nav1.5 was colocalized with DSP at the intercalated discs (IDs). In contrast, Tg-R2834H cardiomyocytes exhibited marked increase of mutant DSP expression at the IDs concomitant with a reduction in Nav1.5 immunoreactive signals. Tg-R2834H cardiomyocytes also revealed an aberration of DSP and desmin colocalizations at the IDs. There were not obvious differences in Cx43 expression between the genotypes, although the redistribution of Cx43 from the IDs to the sarcolemma was evident in Tg-R2834H cardiomyocytes. qPCR results correlated with reduced Nav1.5 mRNA expression in the Tg-R2834H mouse hearts. Conclusions: Defective DSP protein expression in the heart disrupts Nav1.5 localization and expression, implying an interaction between DSP and Nav1.5 to orchestrate normal mechanical and electrical coupling. Further electrophysiology studies to assess whole-cell Na + currents in these cardiomyocytes will provide insight into DSP and Nav1.5 interaction.

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