title: Epigenetic Treatment of Persistent Viral Infections.
abstract: Preclinical Research Approximately 2,500 years ago, Hippocrates used the word herpes as a medical term to describe lesions that appeared to creep or crawl on the skin, advocating heat as a possible treatment. During the last 50 years, pharmaceutical research has made great strides, and therapeutic options have expanded to include small molecule antiviral agents, protease inhibitors, preventive vaccines for a handful of the papillomaviruses, and even cures for hepatitis C virus infections. However, effective treatments for persistent and recurrent viral infections, particularly the highly prevalent herpesviruses, continue to represent a significant unmet medical need, affecting the majority of the world's population. Exploring the population diversity of the human microbiome and the effects its compositional variances have on the immune system, health, and disease are the subjects of intense investigational research and study. Among the collection of viruses, bacteria, fungi, and single-cell eukaryotes that comprise the human microbiome, the virome has been grossly understudied relative to the influence it exerts on human pathophysiology, much as mitochondria have until recently failed to receive the attention they deserve, given their critical biomedical importance. Fortunately, cellular epigenetic machinery offers a wealth of druggable targets for therapeutic intervention in numerous disease indications, including those outlined above. With advances in synthetic biology, engineering our body's commensal microorganisms to seek out and destroy pathogenic species is clearly on the horizon. This is especially the case given recent breakthroughs in genetic manipulation with tools such as the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated) gene-editing platforms. Tying these concepts together with our previous work on the microbiome and neurodegenerative and neuropsychiatric diseases, we suggest that, because mammalian cells respond to a viral infection by triggering a cascade of antiviral innate immune responses governed substantially by the cell's mitochondria, small molecule carnitinoids represent a new class of therapeutics with potential widespread utility against many infectious insults. Drug Dev Res 78 : 24-36, 2017.   © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, University of California San Francisco, San Francisco, California.
authors.forename: Walter H
authors.initials: WH
authors.lastname: Moos
authors.affiliation: Department of Biological Sciences, College of Arts and Sciences, The University of Alabama, Tuscaloosa, Alabama.
authors.forename: Carl A
authors.initials: CA
authors.lastname: Pinkert
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, Alabama.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Irwin
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.|Boston University School of Medicine, Cancer Research Center, Boston, Massachusetts.
authors.forename: Douglas V
authors.initials: DV
authors.lastname: Faller
authors.affiliation: Bridgewater College, Bridgewater, Virginia.
authors.forename: Krishna
authors.initials: K
authors.lastname: Kodukula
authors.affiliation: Department of Ophthalmology, New York University School of Medicine, New York.
authors.forename: Ioannis P
authors.initials: IP
authors.lastname: Glavas
authors.affiliation: Boston University School of Medicine, Cancer Research Center, Boston, Massachusetts.|PhenoMatriX, Boston, Massachusetts.
authors.forename: Kosta
authors.initials: K
authors.lastname: Steliou
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D044127:Epigenesis, Genetic / Q000187:drug effects; D000072669:Gene Editing; D006801:Humans; D007109:Immunity; D064307:Microbiota; D054852:Small Molecule Libraries / Q000494:pharmacology* / Q000627:therapeutic use; D058615:Synthetic Biology; D014777:Virus Diseases / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D014780:Viruses / Q000187:drug effects / Q000235:genetics*
chemical_list: D000890:Anti-Infective Agents; D054852:Small Molecule Libraries
keywords: CRISPR/Cas9; carnitinoid; druggable target; gene editing; herpesvirus; infection; innate immune system; microbiome; mitochondria; neurodegenerative disease; neuropsychiatric disease; pathogenic species; pathophysiology; synthetic biology; therapeutic intervention; virome