scholarly journals Viruses and Autoimmunity: A Review on the Potential Interaction and Molecular Mechanisms

Viruses ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 762 ◽  
Author(s):  
Maria K. Smatti ◽  
Farhan S. Cyprian ◽  
Gheyath K. Nasrallah ◽  
Asmaa A. Al Thani ◽  
Ruba O. Almishal ◽  
...  
Keyword(s):  
Immune Responses ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Influenza A ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Molecular Mimicry ◽  
Experimental Studies ◽  
Onset Time ◽  
Protective Effects

For a long time, viruses have been shown to modify the clinical picture of several autoimmune diseases, including type 1 diabetes (T1D), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren’s syndrome (SS), herpetic stromal keratitis (HSK), celiac disease (CD), and multiple sclerosis (MS). Best examples of viral infections that have been proposed to modulate the induction and development of autoimmune diseases are the infections with enteric viruses such as Coxsackie B virus (CVB) and rotavirus, as well as influenza A viruses (IAV), and herpesviruses. Other viruses that have been studied in this context include, measles, mumps, and rubella. Epidemiological studies in humans and experimental studies in animal have shown that viral infections can induce or protect from autoimmunopathologies depending on several factors including genetic background, host-elicited immune responses, type of virus strain, viral load, and the onset time of infection. Still, data delineating the clear mechanistic interaction between the virus and the immune system to induce autoreactivity are scarce. Available data indicate that viral-induced autoimmunity can be activated through multiple mechanisms including molecular mimicry, epitope spreading, bystander activation, and immortalization of infected B cells. Contrarily, the protective effects can be achieved via regulatory immune responses which lead to the suppression of autoimmune phenomena. Therefore, a better understanding of the immune-related molecular processes in virus-induced autoimmunity is warranted. Here we provide an overview of the current understanding of viral-induced autoimmunity and the mechanisms that are associated with this phenomenon.

scholarly journals Emerging cellular and molecular mechanisms underlying anticancer indications of chrysin

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Marjan Talebi ◽  
Mohsen Talebi ◽  
Tahereh Farkhondeh ◽  
Jesus Simal-Gandara ◽  
Dalia M. Kopustinskiene ◽  
...  
Keyword(s):  
Blood Cells ◽  
Molecular Mechanisms ◽  
Web Of Science ◽  
Experimental Studies ◽  
Protective Effects ◽  
Pharmacological Activities ◽  
Current Review ◽  
Mesh Terms ◽  
Online Databases ◽  
Anti Cancer

AbstractChrysin has been shown to exert several beneficial pharmacological activities. Chrysin has anti-cancer, anti-viral, anti-diabetic, neuroprotective, cardioprotective, hepatoprotective, and renoprotective as well as gastrointestinal, respiratory, reproductive, ocular, and skin protective effects through modulating signaling pathway involved in apoptosis, oxidative stress, and inflammation. In the current review, we discussed the emerging cellular and molecular mechanisms underlying therapeutic indications of chrysin in various cancers. Online databases comprising Scopus, PubMed, Embase, ProQuest, Science Direct, Web of Science, and the search engine Google Scholar were searched for available and eligible research articles. The search was conducted by using MeSH terms and keywords in title, abstract, and keywords. In conclusion, experimental studies indicated that chrysin could ameliorate cancers of the breast, gastrointestinal tract, liver and hepatocytes, bladder, male and female reproductive systems, choroid, respiratory tract, thyroid, skin, eye, brain, blood cells, leukemia, osteoblast, and lymph. However, more studies are needed to enhance the bioavailability of chrysin and evaluate this agent in clinical trial studies. Graphic abstract

scholarly journals Sex differences in severity and mortality from COVID-19: are males more vulnerable?

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ajay Pradhan ◽  
Per-Erik Olsson
Keyword(s):  
Sex Differences ◽  
Immune System ◽  
Immune Responses ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Basic Research ◽  
Contributing Factors ◽  
High Infection ◽  
Males And Females

Abstract Coronavirus disease 2019 (COVID-19) has shown high infection and mortality rates all over the world, and despite the global efforts, there is so far no specific therapy available for COVID-19. Interestingly, while the severity and mortality of COVID-19 are higher in males than in females, the underlying molecular mechanisms are unclear. In this review, we explore sex-related differences that may be contributing factors to the observed male-biased mortality from COVID-19. Males are considered the weaker sex in aspects related to endurance and infection control. Studies show that viral RNA clearance is delayed in males with COVID-19. A recent study has indicated that the testis can harbor coronavirus, and consequently, males show delayed viral clearance. However, the role of testis involvement in COVID-19 severity and mortality needs further research. Males and females show a distinct difference in immune system responses with females eliciting stronger immune responses to pathogens. This difference in immune system responses may be a major contributing factor to viral load, disease severity, and mortality. In addition, differences in sex hormone milieus could also be a determinant of viral infections as estrogen has immunoenhancing effects while testosterone has immunosuppressive effects. The sex-specific severity of COVID-19 infections indicates that further research on understanding the sex differences is needed. Inclusion of both males and females in basic research and clinical trials is required to provide critical information on sex-related differences that may help to better understand disease outcome and therapy.

scholarly journals Interferon pathway lupus risk alleles modulate risk of death from acute COVID-19

2021 ◽  
Author(s):  
Ilona Nln ◽  
Ruth Fernandez-Ruiz ◽  
Theresa L Wampler Muskardin ◽  
Jacqueline L Paredes ◽  
Ashira D Blazer ◽  
...  
Keyword(s):  
African American ◽  
Lupus Erythematosus ◽  
Viral Infections ◽  
Critical Role ◽  
European American ◽  
Type I ◽  
Protective Effects ◽  
Predictive Capacity ◽  
Risk Of Death ◽  
Risk Alleles

Type I interferon (IFN) is critical in our defense against viral infections. Increased type I IFN pathway activation is a genetic risk factor for systemic lupus erythematosus (SLE), and a number of common risk alleles contribute to the high IFN trait. We hypothesized that these common gain-of-function IFN pathway alleles may be associated with protection from mortality in acute COVID-19. We studied patients admitted with acute COVID-19 (751 European-American and 398 African-American ancestry). Ancestral backgrounds were analyzed separately, and mortality after acute COVID-19 was the primary outcome. In European-American ancestry, we found that a haplotype of interferon regulatory factor 5 (IRF5) and alleles of protein kinase cGMP-dependent 1 (PRKG1) were associated with mortality from COVID-19. Interestingly, these were much stronger risk factors in younger patients (OR=29.2 for PRKG1 in ages 45-54). Variants in the IRF7 and IRF8 genes were associated with mortality from COVID-19 in African-American subjects, and these genetic effects were more pronounced in older subjects. Combining genetic information with blood biomarker data such as C-reactive protein, troponin, and D-dimer resulted in significantly improved predictive capacity, and in both ancestral backgrounds the risk genotypes were most relevant in those with positive biomarkers (OR for death between 14 and 111 in high risk genetic/biomarker groups). This study confirms the critical role of the IFN pathway in defense against COVID-19 and viral infections, and supports the idea that some common SLE risk alleles exert protective effects in anti-viral immunity.

scholarly journals Retinoic Acid, Leaky Gut, and Autoimmune Diseases

Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 1016 ◽  
Author(s):  
Leila Abdelhamid ◽  
Xin Luo
Keyword(s):  
Retinoic Acid ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Protective Effects ◽  
Leaky Gut ◽  
Gut Colonization ◽  
Lactobacillus Spp

A leaky gut has been observed in a number of autoimmune diseases including type 1 diabetes, multiple sclerosis, inflammatory bowel disease, and systemic lupus erythematosus. Previous studies from our laboratory have shown that lupus mice also bear a leaky gut and that the intestinal barrier function can be enhanced by gut colonization of probiotics such as Lactobacillus spp. Retinoic acid (RA) can increase the relative abundance of Lactobacillus spp. in the gut. Interestingly, RA has also been shown to strengthen the barrier function of epithelial cells in vitro and in the absence of probiotic bacteria. These reports bring up an interesting question of whether RA exerts protective effects on the intestinal barrier directly or through regulating the microbiota colonization. In this review, we will discuss the roles of RA in immunomodulation, recent literature on the involvement of a leaky gut in different autoimmune diseases, and how RA shapes the outcomes of these diseases.

scholarly journals Molecular mechanisms of induction and acceleration of autoimmunity by microorganisms

2021 ◽  
Vol 20 (1) ◽  
pp. 99-113
Author(s):  
E. P. Kiseleva ◽  
K. I. Mikhailopulo ◽  
G. I. Novik ◽  
N. F. Soroka
Keyword(s):  
T Cells ◽  
Autoimmune Diseases ◽  
Molecular Mechanisms ◽  
Molecular Mimicry ◽  
Ecological Factors ◽  
Infectious Agents ◽  
National Academy Of Sciences ◽  
Adjuvant Effect ◽  
Host Infection ◽  
Cryptic Epitopes

Infectious agents are well-known ecological factors inducing/accelerating human autoimmune diseases. Host infection by a pathogen can lead to autoimmunity via multiple mechanisms: molecular mimicry; epitope spreading and presentation of cryptic epitopes of self-antigen owing to lysis of self-tissue by persisting pathogen or immune cells; bystander activation, adjuvant effect of pathogens as a result of non-specific activation of immune system; polyclonal activation of B-cells by chronic infection; activation of T-cells by bacterial superantigens. Infectious agents and nonpathogenic microorganisms can also protect from autoimmune diseases via activation of regulatory T-cells and displacement of balance between two classes of T helper cells in favor of Th2. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Institute of Bioorganic Сhemistry, National Academy of Sciences of Belarus. 

scholarly journals Pathogenesis of Autoimmune Hepatitis—Cellular and Molecular Mechanisms

2021 ◽  
Vol 22 (24) ◽  
pp. 13578
Author(s):  
Claudia Sirbe ◽  
Gelu Simu ◽  
Iulia Szabo ◽  
Alina Grama ◽  
Tudor Lucian Pop
Keyword(s):  
Autoimmune Hepatitis ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
De Novo ◽  
Molecular Mimicry ◽  
Treg Cells ◽  
Clinical Aspects ◽  
Autoantibody Production ◽  
Genetic Traits ◽  
First Line Therapy

Pediatric autoimmune liver disorders include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is an idiopathic disease characterized by immune-mediated hepatocyte injury associated with the destruction of liver cells, causing inflammation, liver failure, and fibrosis, typically associated with autoantibodies. The etiology of AIH is not entirely unraveled, but evidence supports an intricate interaction among genetic variants, environmental factors, and epigenetic modifications. The pathogenesis of AIH comprises the interaction between specific genetic traits and molecular mimicry for disease development, impaired immunoregulatory mechanisms, including CD4+ T cell population and Treg cells, alongside other contributory roles played by CD8+ cytotoxicity and autoantibody production by B cells. These findings delineate an intricate pathway that includes gene to gene and gene to environment interactions with various drugs, viral infections, and the complex microbiome. Epigenetics emphasizes gene expression through hereditary and reversible modifications of the chromatin architecture without interfering with the DNA sequence. These alterations comprise DNA methylation, histone transformations, and non-coding small (miRNA) and long (lncRNA) RNA transcriptions. The current first-line therapy comprises prednisolone plus azathioprine to induce clinical and biochemical remission. Further understanding of the cellular and molecular mechanisms encountered in AIH may depict their impact on clinical aspects, detect biomarkers, and guide toward novel, effective, and better-targeted therapies with fewer side effects.

scholarly journals Distinct Intracellular Trafficking of Hepatitis C Virus in Myeloid and Plasmacytoid Dendritic Cells

2010 ◽  
Vol 84 (17) ◽  
pp. 8964-8969 ◽  
Author(s):  
Mélanie Lambotin ◽  
Thomas F. Baumert ◽  
Heidi Barth
Keyword(s):  
Dendritic Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Immune Responses ◽  
Intracellular Trafficking ◽  
Antigen Processing ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Antigen Uptake ◽  
Antigen Processing And Presentation

ABSTRACT Dendritic cells (DCs) are of pivotal importance for the initiation of immune responses to control and eliminate viral infections. The molecular mechanisms of hepatitis C virus (HCV) antigen uptake and processing by blood DCs are poorly defined. Here we show that human blood DC subsets acquire HCV independent of the classical HCV entry factors. Following HCV uptake, human plasmacytoid and myeloid DC subsets deliver HCV antigen into distinct endocytotic compartments, which are dedicated to presentation to CD4+ or CD8+ T cells. Our findings support a model of HCV antigen processing and presentation in which DC subsets fulfill distinct functions.

scholarly journals Pemphigus Vulgaris Following Influenza: A Case Report

2019 ◽  
Vol 3 (6) ◽  
pp. 418-422
Author(s):  
Kristen Bice ◽  
Channing Hood ◽  
Rawaa Almukhtar ◽  
Michelle Gerdes ◽  
Pamela Martin ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Case Report ◽  
Autoimmune Disease ◽  
Influenza Vaccine ◽  
Mucous Membrane ◽  
Influenza A ◽  
Viral Infections ◽  
Molecular Mimicry ◽  
Pemphigus Vulgaris ◽  
Epitope Spreading

Viruses have long been implicated as potential triggers of autoimmune disease. In the case of pemphigus vulgaris, members of the herpesviridae family are often associated with its development. There have also been reports of pemphigus being triggered by the influenza vaccine. We report a case of a 17-year-old male who developed mucous membrane-predominant pemphigus vulgaris after testing positive for the influenza virus and discuss proposed hypotheses for the association between viral infections and autoimmunity, such as molecular mimicry and epitope spreading.

scholarly journals Dual Effect of Organogermanium Compound THGP on RIG-I-Mediated Viral Sensing and Viral Replication during Influenza a Virus Infection

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1674
Author(s):  
Sunanda Baidya ◽  
Yoko Nishimoto ◽  
Seiichi Sato ◽  
Yasuhiro Shimada ◽  
Nozomi Sakurai ◽  
...  
Keyword(s):  
Immune Responses ◽  
Influenza A ◽  
Viral Infections ◽  
Genome Replication ◽  
Type I ◽  
Innate Immune Responses ◽  
Viral Polymerase ◽  
Microbial Infections ◽  
Viral Genome Replication ◽  
Vesicular Stomatitis

The interaction of viral nucleic acid with protein factors is a crucial process for initiating viral polymerase-mediated viral genome replication while activating pattern recognition receptor (PRR)-mediated innate immune responses. It has previously been reported that a hydrolysate of Ge-132, 3-(trihydroxygermyl) propanoic acid (THGP), shows a modulatory effect on microbial infections, inflammation, and immune responses. However, the detailed mechanism by which THGP can modify these processes during viral infections remained unknown. Here, we show that THGP can specifically downregulate type I interferon (IFN) production in response to stimulation with a cytosolic RNA sensor RIG-I ligand 5′-triphosphate RNA (3pRNA) but not double-stranded RNA, DNA, or lipopolysaccharide. Consistently, treatment with THGP resulted in the dose-dependent suppression of type I IFN induction upon infections with influenza virus (IAV) and vesicular stomatitis virus, which are known to be mainly sensed by RIG-I. Mechanistically, THGP directly binds to the 5′-triphosphate moiety of viral RNA and competes with RIG-I-mediated recognition. Furthermore, we found that THGP can directly counteract the replication of IAV but not EMCV (encephalitismyocarditis virus), by inhibiting the interaction of viral polymerase with RNA genome. Finally, IAV RNA levels were significantly reduced in the lung tissues of THGP-treated mice when compared with untreated mice. These results suggest a possible therapeutic implication of THGP and show direct antiviral action, together with the suppressive activity of innate inflammation.

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