Epigenetic basis of infectious diseases

Infection refers to the invasion of the body by pathogenic microorganisms including viruses, bacteria, fungi, protozoa, and worms. Infectious diseases are the major cause of morbidity and mortality globally and represent a major threat to humankind. Infection is known to be able to profoundly alter the epigenetic state of the infected tissue. Cellular epigenome like DNA methylation and histone modification patterns is responsive to the pathogens. Host epigenetic perturbation has been evident in response to coronavirus disease-19 (COVID-19). Coronaviruses, such as MERS-CoV and SARS-CoV-1, cause host tissue epigenetic alterations by antagonizing host antigen presentation or activating interferon-response genes. The vulnerability of the elderly to SARS-CoV-2 has been linked to the effect of the epigenome on viral entry. Although numerous studies have addressed the impact of infection-induced host tissue epigenetic changes in cancer development, the broader significance of such changes remains unclear. This chapter presents novel insights on how persistent microbial infections hijack host nuclear functions and take advantage of the cellular epigenetic network to ensure microbial replication, persistence, and evasion from the host immune response. © 2023 Elsevier Inc. All rights reserved.

Histones: The critical players in innate immunity.

The highly conserved histones in different species seem to represent a very ancient and universal innate host defense system against microorganisms in the biological world. Histones are the essential part of nuclear matter and act as a control switch for DNA transcription. However, histones are also found in the cytoplasm, cell membranes, and extracellular fluid, where they function as host defenses and promote inflammatory responses. In some cases, extracellular histones can act as damage-associated molecular patterns (DAMPs) and bind to pattern recognition receptors (PRRs), thereby triggering innate immune responses and causing initial organ damage. Histones and their fragments serve as antimicrobial peptides (AMPs) to directly eliminate bacteria, viruses, fungi, and parasites in vitro and in vivo. Histones are also involved in phagocytes-related innate immune response as components of neutrophil extracellular traps (NETs), neutrophil activators, and plasminogen receptors. In addition, as a considerable part of epigenetic regulation, histone modifications play a vital role in regulating the innate immune response and expression of corresponding defense genes. Here, we review the regulatory role of histones in innate immune response, which provides a new strategy for the development of antibiotics and the use of histones as therapeutic targets for inflammatory diseases, sepsis, autoimmune diseases, and COVID-19.

Understanding the epigenetic mechanisms in SARS CoV-2 infection and potential therapeutic approaches.

COVID-19 pandemic caused by the Severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) has inflicted a global health challenge. Although the overwhelming escalation of mortality seen during the initial phase of the pandemic has reduced, emerging variants of SARS-CoV-2 continue to impact communities worldwide. Several studies have highlighted the association of gene specific epigenetic modifications in host cells with the pathogenesis and severity of the disease. Therefore, alongside the investigations into the virology and pathogenesis of SARS-CoV-2 infection, understanding the epigenetic mechanisms related to the disease is crucial for the rational design of effective targeted therapies. Here, we discuss the interaction of SARS-CoV-2 with the various epigenetic regulators and their subsequent contribution to the risk of disease severity and dysfunctional immune responses. Finally, we also highlight the use of epigenetically targeted drugs for the potential therapeutic interventions capable of eliminating viral infection and/or build effective immunity against it.

Epigenetic-related effects of COVID-19 on the human cells.

Epigenetics related to the various pathways which show long-term impacts on the gene expression patterns without alterations in nucleotide sequences. Over the last decade, epigenetics advanced significantly in the science of biology, oncology, innate immunity as well as pathogens and infectious diseases. In the present review, we aimed to review the relationships between covid19 and epigenetic alterations of the infected cells. Corona virus is one of the known infectious diseases causes respiratory infection, such as pneumonia, and coughing while in animal, it causes diarrhea and upper respiratory disorders. This virus could be transmitted human to human or human to animal with droplets, it translocate via membrane ACE-2 exopeptidase in to the host cells. In conclusion, hypomethylation of Angiotensin II Converting Enzyme (ACE II) possibly upregulates its expression, which will enhance the possibility of SARS-CoV-2 infection.

Epigenetic regulation of autophagy in coronavirus disease 2019 (COVID-19).

The coronavirus disease 2019 (COVID-19) pandemic has become the most serious global public health issue in the past two years, requiring effective therapeutic strategies. This viral infection is a contagious disease caused by new coronaviruses (nCoVs), also called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Autophagy, as a highly conserved catabolic recycling process, plays a significant role in the growth and replication of coronaviruses (CoVs). Therefore, there is great interest in understanding the mechanisms that underlie autophagy modulation. The modulation of autophagy is a very complex and multifactorial process, which includes different epigenetic alterations, such as histone modifications and DNA methylation. These mechanisms are also known to be involved in SARS-CoV-2 replication. Thus, molecular understanding of the epigenetic pathways linked with autophagy and COVID-19, could provide novel therapeutic targets for COVID-19 eradication. In this context, the current review highlights the role of epigenetic regulation of autophagy in controlling COVID-19, focusing on the potential therapeutic implications.

2022 Southern Medical Research Conference

The proceedings contain 593 papers. The topics discussed include: association of transthyretin VAL122ILE variant with incident heart failure and mortality among Black Americans: insights from the regards study;vitamin d modulates histone modifications governing the natriuretic peptide receptor-a gene;cell to cell communication through entanglement and superconductivity improving left ventricular function in an uncoupled state;association of serum lipid levels with COVID-19 infection, severity and mortality;impaired glucose tolerance in guanylyl cyclase/natriuretic peptide receptor-a gene-knockout and gene-duplication mutant mice;meta-analysis of randomized vs observational studies of the effects of invasive therapy in patients with non-ST-elevation myocardial infarction and chronic kidney disease;a retrospective analysis of mortality in adult patients with acute coronary syndrome and cardiogenic shock requiring temporary mechanical circulatory support;and mitochondrial myopathy mimicking Guillain-Barre syndrome in a 21-year-old graduate student.

How to Slow down the Ticking Clock: Age-Associated Epigenetic Alterations and Related Interventions to Extend Life Span.

Epigenetic alterations pose one major hallmark of organismal aging. Here, we provide an overview on recent findings describing the epigenetic changes that arise during aging and in related maladies such as neurodegeneration and cancer. Specifically, we focus on alterations of histone modifications and DNA methylation and illustrate the link with metabolic pathways. Age-related epigenetic, transcriptional and metabolic deregulations are highly interconnected, which renders dissociating cause and effect complicated. However, growing amounts of evidence support the notion that aging is not only accompanied by epigenetic alterations, but also at least in part induced by those. DNA methylation clocks emerged as a tool to objectively determine biological aging and turned out as a valuable source in search of factors positively and negatively impacting human life span. Moreover, specific epigenetic signatures can be used as biomarkers for age-associated disorders or even as targets for therapeutic approaches, as will be covered in this review. Finally, we summarize recent potential intervention strategies that target epigenetic mechanisms to extend healthy life span and provide an outlook on future developments in the field of longevity research.

Epigenetic regulation in antiviral innate immunity.

Emerging life-threatening viruses have posed great challenges to public health. It is now increasingly clear that epigenetics plays a role in shaping host-virus interactions and there is a great need for a more thorough understanding of these intricate interactions through the epigenetic lens, which may represent potential therapeutic opportunities in the clinic. In this review, we highlight the current understanding of the roles of key epigenetic regulators - chromatin remodeling and histone modification - in modulating chromatin openness during host defense against virus. We also discuss how the RNA modification m6A (N6-methyladenosine) affects fundamental aspects of host-virus interactions. We conclude with future directions for uncovering more detailed functions that epigenetic regulation exerts on both host cells and viruses during infection.

Deciphering epigenetic(s) role in modulating susceptibility to and severity of COVID-19 infection and/or outcome: a systematic rapid review.

COVID-19 pandemic waves hitting worldwide result in drastic postinfection complications with interindividual variations, which raised the question for the cause of these observed variations. This urged to think "the impact of environment-affected genes"? In an attempt to unravel the impact of environment-affected genes, a systematic rapid review was conducted to study "the impact of host or viral epigenetic modulation on COVID-19 infection susceptibility and/or outcome." Electronic databases including Web of Science, SCOPUS, Cochrane Central Register of Controlled Trials, PubMed, and Google Scholar, and other databases were searched. The search strings included "COVID-19" OR "SARS-CoV-2" AND (Epigenetics'). Articles with randomized clinical trials (RCTs) and observational study designs, conducted on humans and available in the English language, were selected, with respect to "The interplay between the SARS-CoV-2 virus and Epigenetics" published from 2020 to February 2021 (but not limited to 2020, being expanded to 2015). Database search yielded 1330 articles; after screening, exclusion, and further filtrations, 51 articles were included. Susceptibility to COVID-19 infection is related to the viral-microRNAs (miRNAs) which alter virulence of the transmitted SARS-CoV-2 strains and impact host-miRNA-related innate immunity. Host-DNA methylation and/or chromatin remodeling may be implicated in severe cytokine storm that can ultimately results in fatal outcome.

Exposome and Immunity Training: How Pathogen Exposure Order Influences Innate Immune Cell Lineage Commitment and Function.

Immune memory is a defining characteristic of adaptive immunity, but recent work has shown that the activation of innate immunity can also improve responsiveness in subsequent exposures. This has been coined "trained immunity" and diverges with the perception that the innate immune system is primitive, non-specific, and reacts to novel and recurrent antigen exposures similarly. The "exposome" is the cumulative exposures (diet, exercise, environmental exposure, vaccination, genetics, etc.) an individual has experienced and provides a mechanism for the establishment of immune training or immunotolerance. It is becoming increasingly clear that trained immunity constitutes a delicate balance between the dose, duration, and order of exposures. Upon innate stimuli, trained immunity or tolerance is shaped by epigenetic and metabolic changes that alter hematopoietic stem cell lineage commitment and responses to infection. Due to the immunomodulatory role of the exposome, understanding innate immune training is critical for understanding why some individuals exhibit protective phenotypes while closely related individuals may experience immunotolerant effects (e.g., the order of exposure can result in completely divergent immune responses). Research on the exposome and trained immunity may be leveraged to identify key factors for improving vaccination development, altering inflammatory disease development, and introducing potential new prophylactic treatments, especially for diseases such as COVID-19, which is currently a major health issue for the world. Furthermore, continued exposome research may prevent many deleterious effects caused by immunotolerance that frequently result in host morbidity or mortality.