scholarly journals Mechanisms of Proteinuria in HIV

2021 ◽  
Vol 8 ◽  
Author(s):  
Gentzon Hall ◽  
Christina M. Wyatt
Keyword(s):  
Kidney Disease ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Glomerular Diseases ◽  
Animal Models Of Disease ◽  
Filtration Barrier ◽  
Models Of Disease ◽  
Susceptible Populations

Proteinuria is common in the setting of HIV infection, and may reflect comorbid kidney disease, treatment-related nephrotoxicity, and HIV-related glomerular diseases. The mechanisms of podocyte and tubulointerstial injury in HIV-associated nephropathy (HIVAN) have been the subject of intense investigation over the past four decades. The pathologic contributions of viral gene expression, dysregulated innate immune signaling, and ancestry-driven genetic risk modifiers have been explored in sophisticated cellular and whole animal models of disease. These studies provide evidence that injury-induced podocyte dedifferentiation, hyperplasia, cytoskeletal dysregulation, and apoptosis may cause the loss of glomerular filtration barrier integrity and slit diaphragm performance that facilitates proteinuria and tuft collapse in HIVAN. Although the incidence of HIVAN has declined with the introduction of antiretroviral therapy, the collapsing FSGS lesion has been observed in the context of other viral infections and chronic autoimmune disorders, and with the use of interferon-based therapies in genetically susceptible populations. This highlights the fact that the lesion is not specific to HIVAN and that the role of the immune system in aggravating podocyte injury warrants further exploration. This review will summarize our progress in characterizing the molecular mechanisms of podocyte dysfunction in HIVAN and other forms of HIV-associated kidney disease.

scholarly journals Viral miRNAs as Active Players and Participants in Tumorigenesis

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 358 ◽  
Author(s):  
Alessia Gallo ◽  
Vitale Miceli ◽  
Matteo Bulati ◽  
Gioacchin Iannolo ◽  
Flavia Contino ◽  
...  
Keyword(s):  
Viral Infections ◽  
Human Cancer ◽  
Scientific Evidence ◽  
Adaptive Immune System ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Cellular Mirnas ◽  
Viral Mirnas ◽  
Human Cancers ◽  
Cellular Pathways

The theory that viruses play a role in human cancers is now supported by scientific evidence. In fact, around 12% of human cancers, a leading cause of morbidity and mortality in some regions, are attributed to viral infections. However, the molecular mechanism remains complex to decipher. In recent decades, the uncovering of cellular miRNAs, with their invaluable potential as diagnostic and prognostic biomarkers, has increased the number of studies being conducted regarding human cancer diagnosis. Viruses develop clever mechanisms to succeed in the maintenance of the viral life cycle, and some viruses, especially herpesviruses, encode for miRNA, v-miRNAs. Through this viral miRNA, the viruses are able to manipulate cellular and viral gene expression, driving carcinogenesis and escaping the host innate or adaptive immune system. In this review, we have discussed the main viral miRNAs and virally influenced cellular pathways, and their capability to drive carcinogenesis.

scholarly journals Early Glomerular Filtration Defect and Severe Renal Disease in Podocin-Deficient Mice

2004 ◽  
Vol 24 (2) ◽  
pp. 550-560 ◽  
Author(s):  
Séverine Roselli ◽  
Laurence Heidet ◽  
Mireille Sich ◽  
Anna Henger ◽  
Matthias Kretzler ◽  
...  
Keyword(s):  
Renal Disease ◽  
Glomerular Filtration ◽  
Molecular Mechanisms ◽  
Slit Diaphragm ◽  
Vascular Lesions ◽  
Suitable Model ◽  
Glomerular Diseases ◽  
Filtration Barrier ◽  
Severe Renal Disease

ABSTRACT Podocytes are specialized epithelial cells covering the basement membrane of the glomerulus in the kidney. The molecular mechanisms underlying the role of podocytes in glomerular filtration are still largely unknown. We generated podocin-deficient (Nphs2 −/−) mice to investigate the function of podocin, a protein expressed at the insertion of the slit diaphragm in podocytes and defective in a subset of patients with steroid-resistant nephrotic syndrome and focal and segmental glomerulosclerosis. Nphs2 −/− mice developed proteinuria during the antenatal period and died a few days after birth from renal failure caused by massive mesangial sclerosis. Electron microscopy revealed the extensive fusion of podocyte foot processes and the lack of a slit diaphragm in the remaining foot process junctions. Using real-time PCR and immunolabeling, we showed that the expression of other slit diaphragm components was modified in Nphs2 −/− kidneys: the expression of the nephrin gene was downregulated, whereas that of the ZO1 and CD2AP genes appeared to be upregulated. Interestingly, the progression of the renal disease, as well as the presence or absence of renal vascular lesions, depends on the genetic background. Our data demonstrate the crucial role of podocin in the establishment of the glomerular filtration barrier and provide a suitable model for mapping and identifying modifier genes involved in glomerular diseases caused by podocyte injuries.

scholarly journals GPRC5b Modulates Inflammatory Response in Glomerular Diseases via NF-κB Pathway

2019 ◽  
Vol 30 (9) ◽  
pp. 1573-1586 ◽  
Author(s):  
Sonia Zambrano ◽  
Katja Möller-Hackbarth ◽  
Xidan Li ◽  
Patricia Q. Rodriguez ◽  
Emmanuelle Charrin ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Knockout Mice ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Inflammatory Cells ◽  
Data Sets ◽  
Glomerular Diseases ◽  
Filtration Barrier ◽  
Inflammatory Processes

BackgroundInflammatory processes play an important role in the pathogenesis of glomerulopathies. Finding novel ways to suppress glomerular inflammation may offer a new way to stop disease progression. However, the molecular mechanisms that initiate and drive inflammation in the glomerulus are still poorly understood.MethodsWe performed large-scale gene expression profiling of glomerulus-associated G protein–coupled receptors (GPCRs) to identify new potential therapeutic targets for glomerulopathies. The expression of Gprc5b in disease was analyzed using quantitative PCR and immunofluorescence, and by analyzing published microarray data sets. In vivo studies were carried out in a podocyte-specific Gprc5b knockout mouse line. Mechanistic studies were performed in cultured human podocytes.ResultsWe identified an orphan GPCR, Gprc5b, as a novel gene highly enriched in podocytes that was significantly upregulated in common human glomerulopathies, including diabetic nephropathy, IgA nephropathy, and lupus nephritis. Similar upregulation of Gprc5b was detected in LPS-induced nephropathy in mice. Studies in podocyte-specific Gprc5b knockout mice showed that Gprc5b was not essential for normal development of the glomerular filtration barrier. However, knockout mice were partially protected from LPS-induced proteinuria and recruitment of inflammatory cells. Mechanistically, RNA sequencing in Gprc5b knockouts mice and experiments in cultured human podocytes showed that Gpr5cb regulated inflammatory response in podocytes via NF-κB signaling.ConclusionsGPRC5b is a novel podocyte-specific receptor that regulates inflammatory response in the glomerulus by modulating the NF-κB signaling pathway. Upregulation of Gprc5b in human glomerulopathies suggests that it may play a role in their pathogenesis.

Molecular mechanisms of virus-mediated cytopathology

1983 ◽  
Vol 303 (1114) ◽  
pp. 167-176 ◽  
Keyword(s):  
Protein Synthesis ◽  
Molecular Mechanisms ◽  
Viral Gene Expression ◽  
Nucleocytoplasmic Transport ◽  
Host Protein ◽  
Viral Gene ◽  
Animal Cells ◽  
Viral Mrnas ◽  
Protein Factor ◽  
Host Protein Synthesis

Lytic virus infections of animal cells usually lead to a variety of morphological and biochemical lesions that include inhibition of cellular macromolecular syntheses. These cytopathic effects vary in intensity for different virus-cell combinations and probably involve several overlapping mechanisms. Inhibition may be mediated by components of parental virions or require viral gene expression. In many infected cell systems the initiation of host protein synthesis is selectively blocked. This shut-off phenomenon can result from changes in membrane permeability that alter the intracellular ionic environment in favour of viral expression, successful competition of viral mRNAs for limited translational components, or a decrease in the level of cell mRNAs by inhibition of synthesis or nucleocytoplasmic transport. However, the early onset and rapidity of virus-induced inhibition, sometimes under non-permissive conditions, implies more direct mechanisms of translational inactivation. These include enhanced degradation of cellular mRNAs or specific modification of the translation apparatus in infected cells. A dramatic example of the latter occurs in poliovirus-infected HeLa cells in which intact, functional cellular mRNA persists but host protein synthesis is almost completely inhibited. The virus-induced defect is apparently related to inactivation of a protein factor that binds to the 5' end of m7G-capped mRNAs and is required for translation of host (capped) mRNAs but not for the expression of poliovirus RNA, which is not capped. This process and other possible molecular mechanisms of virus-mediated cytopathology are discussed.

scholarly journals Norovirus gene expression and replication

2014 ◽  
Vol 95 (2) ◽  
pp. 278-291 ◽  
Author(s):  
Lucy G. Thorne ◽  
Ian G. Goodfellow
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Rna Viruses ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Genome Replication ◽  
Murine Norovirus ◽  
Technological Advances ◽  
Viral Genome Replication ◽  
Cell Processes

Noroviruses are small, positive-sense RNA viruses within the family Caliciviridae, and are now accepted widely as a major cause of acute gastroenteritis in both developed and developing countries. Despite their impact, our understanding of the life cycle of noroviruses has lagged behind that of other RNA viruses due to the inability to culture human noroviruses (HuNVs). Our knowledge of norovirus biology has improved significantly over the past decade as a result of numerous technological advances. The use of a HuNV replicon, improved biochemical and cell-based assays, combined with the discovery of a murine norovirus capable of replication in cell culture, has improved greatly our understanding of the molecular mechanisms of norovirus genome translation and replication, as well as the interaction with host cell processes. In this review, the current state of knowledge of the intracellular life of noroviruses is discussed with particular emphasis on the mechanisms of viral gene expression and viral genome replication.

scholarly journals The Current Status of Latency Reversing Agents for HIV-1 Remission

2021 ◽  
Vol 8 (1) ◽  
pp. 491-514
Author(s):  
Anthony Rodari ◽  
Gilles Darcis ◽  
Carine M. Van Lint
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Viral Gene Expression ◽  
Current Status ◽  
Viral Gene ◽  
Latently Infected ◽  
Hiv 1 ◽  
Reversing Agents

Combinatory antiretroviral therapy (cART) reduces human immunodeficiency virus type 1 (HIV-1) replication but is not curative because cART interruption almost invariably leads to a rapid rebound of viremia due to the persistence of stable HIV-1-infected cellular reservoirs. These reservoirs are mainly composed of CD4+ T cells harboring replication-competent latent proviruses. A broadly explored approach to reduce the HIV-1 reservoir size, the shock and kill strategy, consists of reactivating HIV-1 gene expression from the latently infected cellular reservoirs (the shock), followed by killing of the virus-producing infected cells (the kill). Based on improved understanding of the multiple molecular mechanisms controlling HIV-1 latency, distinct classes of latency reversing agents (LRAs) have been studied for their efficiency to reactivate viral gene expression in in vitro and ex vivo cell models. Here, we provide an up-to-date review of these different mechanistic classes of LRAs and discuss optimizations of the shock strategy by combining several LRAs simultaneously or sequentially.

scholarly journals Understanding the Mechanisms of Proteinuria: Therapeutic Implications

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Jorge E. Toblli ◽  
P. Bevione ◽  
F. Di Gennaro ◽  
L. Madalena ◽  
G. Cao ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Glomerular Filtration ◽  
Strong Predictor ◽  
Large Body ◽  
Glomerular Filtration Barrier ◽  
Glomerular Diseases ◽  
Filtration Barrier ◽  
Wide Range

A large body of evidence indicates that proteinuria is a strong predictor of morbidity, a cause of inflammation, oxidative stress and progression of chronic kidney disease, and development of cardiovascular disease. The processes that lead to proteinuria are complex and involve factors such as glomerular hemodynamic, tubular absorption, and diffusion gradients. Alterations in various different molecular pathways and interactions may lead to the identical clinical end points of proteinuria and chronic kidney disease. Glomerular diseases include a wide range of immune and nonimmune insults that may target and thus damage some components of the glomerular filtration barrier. In many of these conditions, the renal visceral epithelial cell (podocyte) responds to injury along defined pathways, which may explain the resultant clinical and histological changes. The recent discovery of the molecular components of the slit diaphragm, specialized structure of podocyte-podocyte interaction, has been a major breakthrough in understanding the crucial role of the epithelial layer of the glomerular barrier and the pathogenesis of proteinuria. Thispaper provides an overview and update on the structure and function of the glomerular filtration barrier and the pathogenesis of proteinuria, highlighting the role of the podocyte in this setting. In addition, current antiproteinuric therapeutic approaches are briefly commented.

Nanoformulation of Glycyrrhizic acid as a potent antiviral agent against Covid-19

2022 ◽  
Vol 01 ◽  
Author(s):  
Sayani Ghosh ◽  
Prasun Patra
Keyword(s):  
Therapeutic Strategy ◽  
Glycyrrhizic Acid ◽  
Viral Infections ◽  
Antiviral Agent ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Replication Strategy ◽  
Increased Activity

Abstract: In many previous studies, it has been found that liquorice plant (Glycyrrhiza glabra) extracts contain more than 300 natural compounds, most of which are triterpenoids and flavonoids, and had shown promising results in clinical studies for treating many microbial and viral infections. Triterpenoids like glycyrrhizic acid have shown anti-SARS-CoV activity in- vitro. Experimentally, certain glycyrrhizic acid derivatives have shown increased activity by many folds against SARS-associated viruses. These compounds can potentially inhibit the replication cycle of SARS-associated viruses by interfering with the viral gene expression or by inhibiting the spike protein expression, which in turn inhibits the adhesion and entry of the virus. Although the therapeutic has shown great antiviral activity in vitro, but in vivo its efficiency deteriorates till it reaches the liver for metabolism. In the current review, we analyze the unique replication strategy of SARS-CoV-2 and glycyrrhizic acid as a potential drug against SARS-CoV-2. We also discuss possible nano-formulations of glycyrrhizic acid for efficient drug delivery in humans, as a potent therapeutic strategy for COVID-19.

scholarly journals The Diverse Roles of microRNAs at the Host–Virus Interface

Viruses ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 440 ◽  
Author(s):  
Annie Bernier ◽  
Selena Sagan
Keyword(s):  
Gene Expression ◽  
Genome Stability ◽  
Viral Infections ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Transcriptional Level ◽  
Cellular Mirnas ◽  
Antiviral Responses ◽  
Dna And Rna ◽  
Rna Accumulation

MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression at the post-transcriptional level. Through this activity, they are implicated in almost every cellular process investigated to date. Hence, it is not surprising that miRNAs play diverse roles in regulation of viral infections and antiviral responses. Diverse families of DNA and RNA viruses have been shown to take advantage of cellular miRNAs or produce virally encoded miRNAs that alter host or viral gene expression. MiRNA-mediated changes in gene expression have been demonstrated to modulate viral replication, antiviral immune responses, viral latency, and pathogenesis. Interestingly, viruses mediate both canonical and non-canonical interactions with miRNAs to downregulate specific targets or to promote viral genome stability, translation, and/or RNA accumulation. In this review, we focus on recent findings elucidating several key mechanisms employed by diverse virus families, with a focus on miRNAs at the host–virus interface during herpesvirus, polyomavirus, retroviruses, pestivirus, and hepacivirus infections.

scholarly journals Development of “NEC-SD-LAMP,” a New Non-Electrified Infectious Diseases Testing Method

2022 ◽  
Author(s):  
Yusuke Kimura ◽  
Masashi Ikeuchi
Keyword(s):  
Gene Expression ◽  
Melting Point ◽  
Palmitic Acid ◽  
Viral Infections ◽  
Viral Gene Expression ◽  
Isothermal Amplification ◽  
Viral Gene ◽  
Optimal Temperature ◽  
Loop Mediated Isothermal Amplification ◽  
Electric Control

Abstract Here, non-electric-control SalivaDirect loop-mediated isothermal amplification (NEC-SD-LAMP), which can detect infections by analyzing viral gene expression in saliva without electrical control systems, was developed. In this method, viral genes are purified from saliva using SalivaDirect, and gene expression is analyzed by loop-mediated isothermal amplification (LAMP) by adding water to the device, and the results can be visually confirmed. Melting palmitic acid maintains the optimal temperature for the LAMP reaction, as the temperature of palmitic acid is maintained at 62.9°C, its melting point. By taking advantage of the proximity of this melting point to the optimal temperature for LAMP, it is possible to perform LAMP without electricity. Using this method, adenovirus DNA was detected in saliva. Furthermore, the detection limit was 2 copies per µL, indicating that it is possible to detect viral infections in saliva even before the onset of SARS-CoV-2 infection.

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