scholarly journals New Insights into Chikungunya Virus Infection and Pathogenesis

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Vasiliya Kril ◽  
Olivier Aïqui-Reboul-Paviet ◽  
Laurence Briant ◽  
Ali Amara
Keyword(s):  
Chikungunya Virus ◽  
Molecular Mechanisms ◽  
Clinical Manifestations ◽  
Annual Review ◽  
Publication Date ◽  
Nonstructural Proteins ◽  
Chikv Infection ◽  
Replication Complex ◽  
Host Cell Interactions ◽  
Patients Experience

Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus responsible for major outbreaks of disease since 2004 in the Indian Ocean islands, South east Asia, and the Americas. CHIKV causes debilitating musculoskeletal disorders in humans that are characterized by fever, rash, polyarthralgia, and myalgia. The disease is often self-limiting and nonlethal; however, some patients experience atypical or severe clinical manifestations, as well as a chronic rheumatic syndrome. Unfortunately, no efficient antivirals against CHIKV infection are available so far, highlighting the importance of deepening our knowledge of CHIKV host cell interactions and viral replication strategies. In this review, we discuss recent breakthroughs in the molecular mechanisms that regulate CHIKV infection and lay down the foundations to understand viral pathogenesis. We describe the role of the recently identified host factors co-opted by the virus for infection and pathogenesis, and emphasize the importance of CHIKV nonstructural proteins in both replication complex assembly and host immune response evasion. Expected final online publication date for the Annual Review of Virology, Volume 8 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals The Phosphatidylserine Receptor TIM-1 Enhances Authentic Chikungunya Virus Cell Entry

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1828
Author(s):  
Jared Kirui ◽  
Yara Abidine ◽  
Annasara Lenman ◽  
Koushikul Islam ◽  
Yong-Dae Gwon ◽  
...  
Keyword(s):  
Chikungunya Virus ◽  
Molecular Mechanisms ◽  
Rna Virus ◽  
Ectopic Expression ◽  
Point Mutations ◽  
Cell Entry ◽  
Target Cells ◽  
Human Hepatoma Cells ◽  
Chikv Infection ◽  
Phosphatidylserine Receptor

Chikungunya virus (CHIKV) is a re-emerging, mosquito-transmitted, enveloped positive stranded RNA virus. Chikungunya fever is characterized by acute and chronic debilitating arthritis. Although multiple host factors have been shown to enhance CHIKV infection, the molecular mechanisms of cell entry and entry factors remain poorly understood. The phosphatidylserine-dependent receptors, T-cell immunoglobulin and mucin domain 1 (TIM-1) and Axl receptor tyrosine kinase (Axl), are transmembrane proteins that can serve as entry factors for enveloped viruses. Previous studies used pseudoviruses to delineate the role of TIM-1 and Axl in CHIKV entry. Conversely, here, we use the authentic CHIKV and cells ectopically expressing TIM-1 or Axl and demonstrate a role for TIM-1 in CHIKV infection. To further characterize TIM-1-dependent CHIKV infection, we generated cells expressing domain mutants of TIM-1. We show that point mutations in the phosphatidylserine binding site of TIM-1 lead to reduced binding, entry, and infection of CHIKV. Ectopic expression of TIM-1 renders immortalized keratinocytes permissive to CHIKV, whereas silencing of endogenously expressed TIM-1 in human hepatoma cells reduces CHIKV infection. Altogether, our findings indicate that, unlike Axl, TIM-1 readily promotes the productive entry of authentic CHIKV into target cells.

Genetics of Pediatric Immune-Mediated Diseases and Human Immunity

2021 ◽  
Vol 39 (1) ◽  
Author(s):  
Erica G. Schmitt ◽  
Megan A. Cooper
Keyword(s):  
Primary Immunodeficiency ◽  
Bone Marrow Failure ◽  
Clinical Manifestations ◽  
Annual Review ◽  
Publication Date ◽  
Hematopoietic Stem ◽  
Genetic Mechanisms ◽  
Human Immune Response ◽  
Genetically Determined ◽  
Complex Signaling

Primary immunodeficiency diseases (PIDs) are a rapidly growing, heterogeneous group of genetically determined diseases characterized by defects in the immune system. While individually rare, collectively PIDs affect between 1/1,000 and 1/5,000 people worldwide. The clinical manifestations of PIDs vary from susceptibility to infections to autoimmunity and bone marrow failure. Our understanding of the human immune response has advanced by investigation and discovery of genetic mechanisms of PIDs. Studying patients with isolated genetic variants in proteins that participate in complex signaling pathways has led to an enhanced understanding of host response to infection, and mechanisms of autoimmunity and autoinflammation. Identifying genetic mechanisms of PIDs not only furthers immunological knowledge but also benefits patients by dictating targeted therapies or hematopoietic stem cell transplantation. Here, we highlight several of these areas in the field of primary immunodeficiency, with a focus on the most recent advances. Expected final online publication date for the Annual Review of Immunology, Volume 39 is April 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Molecular Force Measurement with Tension Sensors

2021 ◽  
Vol 50 (1) ◽  
Author(s):  
Lisa S. Fischer ◽  
Srishti Rangarajan ◽  
Tanmay Sadhanasatish ◽  
Carsten Grashoff
Keyword(s):  
Molecular Mechanisms ◽  
Force Measurement ◽  
Annual Review ◽  
Publication Date ◽  
Mechanical Forces ◽  
Biophysical Parameters ◽  
Cellular Mechanotransduction ◽  
Molecular Force ◽  
Molecular Forces ◽  
Physical Principles

The ability of cells to generate mechanical forces, but also to sense, adapt to, and respond to mechanical signals, is crucial for many developmental, postnatal homeostatic, and pathophysiological processes. However, the molecular mechanisms underlying cellular mechanotransduction have remained elusive for many decades, as techniques to visualize and quantify molecular forces across individual proteins in cells were missing. The development of genetically encoded molecular tension sensors now allows the quantification of piconewton-scale forces that act upon distinct molecules in living cells and even whole organisms. In this review, we discuss the physical principles, advantages, and limitations of this increasingly popular method. By highlighting current examples from the literature, we demonstrate how molecular tension sensors can be utilized to obtain access to previously unappreciated biophysical parameters that define the propagation of mechanical forces on molecular scales. We discuss how the methodology can be further developed and provide a perspective on how the technique could be applied to uncover entirely novel aspects of mechanobiology in the future. Expected final online publication date for the Annual Review of Biophysics, Volume 50 is May 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Systems Biology of the Vasopressin V2 Receptor: New Tools for Discovery of Molecular Actions of a GPCR

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Lihe Chen ◽  
Hyun Jun Jung ◽  
Arnab Datta ◽  
Euijung Park ◽  
Brian G. Poll ◽  
...  
Keyword(s):  
Systems Biology ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Water Channel ◽  
Peptide Hormone ◽  
Annual Review ◽  
Publication Date ◽  
Large Scale Data ◽  
V2 Receptor ◽  
Scale Data

Systems biology can be defined as the study of a biological process in which all of the relevant components are investigated together in parallel to discover the mechanism. Although the approach is not new, it has come to the forefront as a result of genome sequencing projects completed in the first few years of the current century. It has elements of large-scale data acquisition (chiefly next-generation sequencing–based methods and protein mass spectrometry) and large-scale data analysis (big data integration and Bayesian modeling). Here we discuss these methodologies and show how they can be applied to understand the downstream effects of GPCR signaling, specifically looking at how the neurohypophyseal peptide hormone vasopressin, working through the V2 receptor and PKA activation, regulates the water channel aquaporin-2. The emerging picture provides a detailed framework for understanding the molecular mechanisms involved in water balance disorders, pointing the way to improved treatment of both polyuric disorders and water-retention disorders causing dilutional hyponatremia. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Molecules from the Microbiome

2021 ◽  
Vol 90 (1) ◽  
Author(s):  
Emilee E. Shine ◽  
Jason M. Crawford
Keyword(s):  
Small Molecules ◽  
Molecular Mechanisms ◽  
System Development ◽  
Human Microbiome ◽  
Host Responses ◽  
Annual Review ◽  
Publication Date ◽  
Mechanistic Studies ◽  
Immune System Development ◽  
Interdisciplinary Approaches

The human microbiome encodes a second genome that dwarfs the genetic capacity of the host. Microbiota-derived small molecules can directly target human cells and their receptors or indirectly modulate host responses through functional interactions with other microbes in their ecological niche. Their biochemical complexity has profound implications for nutrition, immune system development, disease progression, and drug metabolism, as well as the variation in these processes that exists between individuals. While the species composition of the human microbiome has been deeply explored, detailed mechanistic studies linking specific microbial molecules to host phenotypes are still nascent. In this review, we discuss challenges in decoding these interaction networks, which require interdisciplinary approaches that combine chemical biology, microbiology, immunology, genetics, analytical chemistry, bioinformatics, and synthetic biology. We highlight important classes of microbiota-derived small molecules and notable examples. An understanding of these molecular mechanisms is central to realizing the potential of precision microbiome editing in health, disease, and therapeutic responses. Expected final online publication date for the Annual Review of Biochemistry, Volume 90 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals MOATAI-VIR - an AI algorithm that predicts severe adverse events and molecular features for COVID-19’s complications

2021 ◽  
Author(s):  
Courtney Astore ◽  
Hongyi Zhou ◽  
Joshy Jacob ◽  
Jeffrey Skolnick
Keyword(s):  
Adverse Events ◽  
Molecular Mechanisms ◽  
Chromosomal Abnormalities ◽  
Clinical Manifestations ◽  
Host Responses ◽  
Molecular Features ◽  
Disease Protein ◽  
Human Proteins ◽  
Severe Adverse Events ◽  
Patients Experience

AbstractFollowing SARS-CoV-2 infection, some COVID-19 patients experience severe adverse events caused by pathogenic host responses. To treat these complications, their underlying etiology must be identified. Thus, a novel AI-based methodology, MOATAI-VIR, which predicts disease-protein-pathway relationships for 22 clinical manifestations attributed to COVID-19 was developed. SARS-CoV-2 interacting human proteins and GWAS identified respiratory failure associated risk genes provide the input from which the mode-of-action (MOA) proteins/pathways of the resulting disease comorbidities are predicted. These comorbidities are then mapped to their clinical manifestations. Three uncharacterized manifestation categories are found: neoplasms, mental and behavioral disorders, and congenital malformations, deformations, and chromosomal abnormalities. The prevalence of neoplasms suggests a possible association between COVID-19 and cancer, whether by shared molecular mechanisms between oncogenesis and viral replication, or perhaps, SARS-CoV-2 is an oncovirus. To assess the molecular basis of each manifestation, the proteins shared across each group of comorbidities were prioritized and subject to global pathway analysis. From these most frequent pathways, the molecular features associated with hallmark COVID-19 phenotypes, such as loss of sense of smell/taste, unusual neurological symptoms, cytokine storm, and blood clots were explored. Results of MOATAI-VIR are available for academic users at: http://pwp.gatech.edu/cssb/MOATAI-VIR/.

Mitochondrial H+ Leak and Thermogenesis

2021 ◽  
Vol 84 (1) ◽  
Author(s):  
Ambre M. Bertholet ◽  
Yuriy Kirichok
Keyword(s):  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Annual Review ◽  
Publication Date ◽  
Uncoupling Protein 1 ◽  
Current Field ◽  
Atp Production ◽  
Metabolic Substrates ◽  
Primary Focus

Mitochondria of all tissues convert various metabolic substrates into two forms of energy: ATP and heat. Historically, the primary focus of research in mitochondrial bioenergetics was on the mechanisms of ATP production, while mitochondrial thermogenesis received significantly less attention. Nevertheless, mitochondrial heat production is crucial for the maintenance of body temperature, regulation of the pace of metabolism, and prevention of oxidative damage to mitochondria and the cell. In addition, mitochondrial thermogenesis has gained significance as a pharmacological target for treating metabolic disorders. Mitochondria produce heat as the result of H+ leak across their inner membrane. This review provides a critical assessment of the current field of mitochondrial H+ leak and thermogenesis, with a focus on the molecular mechanisms involved in the function and regulation of uncoupling protein 1 and the ADP/ATP carrier, the two proteins that mediate mitochondrial H+ leak. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Adipose Tissue Fibrosis in Obesity: Etiology and Challenges

2021 ◽  
Vol 84 (1) ◽  
Author(s):  
Geneviève Marcelin ◽  
Emmanuel L. Gautier ◽  
Karine Clément
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Molecular Mechanisms ◽  
Whole Body ◽  
Annual Review ◽  
Publication Date ◽  
Tissue Fibrosis ◽  
Adipose Tissue Remodeling ◽  
Metabolic Dysfunctions ◽  
Body Energy

Obesity is a chronic and progressive process affecting whole-body energy balance and is associated with comorbidities development. In addition to increased fat mass, obesity induces white adipose tissue (WAT) inflammation and fibrosis, leading to local and systemic metabolic dysfunctions, such as insulin resistance (IR). Accordingly, limiting inflammation or fibrosis deposition may improve IR and glucose homeostasis. Although no targeted therapy yet exists to slow or reverse adipose tissue fibrosis, a number of findings have clarified the underlying cellular and molecular mechanisms. In this review, we highlight adipose tissue remodeling events shown to be associated with fibrosis deposition, with a focus on adipose progenitors involved in obesity-induced healthy as well as unhealthy WAT expansion. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Receptor-Ribosome Coupling: A Link Between Extrinsic Signals and mRNA Translation in Neuronal Compartments

2022 ◽  
Vol 45 (1) ◽  
Author(s):  
Max Koppers ◽  
Christine E. Holt
Keyword(s):  
Intracellular Signaling ◽  
Messenger Rna ◽  
Molecular Mechanisms ◽  
Synapse Formation ◽  
Cell Communication ◽  
Mrna Translation ◽  
Common Mechanism ◽  
Annual Review ◽  
Publication Date ◽  
Spatiotemporal Resolution

Axons receive extracellular signals that help to guide growth and synapse formation during development and to maintain neuronal function and survival during maturity. These signals relay information via cell surface receptors that can initiate local intracellular signaling at the site of binding, including local messenger RNA (mRNA) translation. Direct coupling of translational machinery to receptors provides an attractive way to activate this local mRNA translation and change the local proteome with high spatiotemporal resolution. Here, we first discuss the increasing evidence that different external stimuli trigger translation of specific subsets of mRNAs in axons via receptors and thus play a prominent role in various processes in both developing and mature neurons. We then discuss the receptor-mediated molecular mechanisms that regulate local mRNA translational with a focus on direct receptor-ribosome coupling. We advance the idea that receptor-ribosome coupling provides several advantages over other translational regulation mechanisms and is a common mechanism in cell communication. Expected final online publication date for the Annual Review of Neuroscience, Volume 45 is July 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Enteroviruses and Type 1 Diabetes: Multiple Mechanisms and Factors?

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Richard E. Lloyd ◽  
Manasi Tamhankar ◽  
Åke Lernmark
Keyword(s):  
Type 1 Diabetes ◽  
Molecular Mechanisms ◽  
Subsequent Development ◽  
Annual Review ◽  
Publication Date ◽  
Virus Infections ◽  
Persistent Infections ◽  
Complex Interactions ◽  
Genetic And Environmental Factors

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by insulin deficiency and resultant hyperglycemia. Complex interactions of genetic and environmental factors trigger the onset of autoimmune mechanisms responsible for development of autoimmunity to β cell antigens and subsequent development of T1D. A potential role of virus infections has long been hypothesized, and growing evidence continues to implicate enteroviruses as the most probable triggering viruses. Recent studies have strengthened the association between enteroviruses and development of autoimmunity in T1D patients, potentially through persistent infections. Enterovirus infections may contribute to different stages of disease development. We review data from both human cohort studies and experimental research exploring the potential roles and molecular mechanisms by which enterovirus infections can impact disease outcome. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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