Revealing networks targeted by HSV-1 ncRNAs with in vivo gain-of-function studies

Revealing networks targeted by HSV-1 ncRNAs with in vivo gain-of-function studies

At the turn of the last century, infectious diseases represented an important cause of health morbidity and behavioral changes. A blood RNA signature highlights genes involved in pathways associated with macrophages and lymphocytes: TGF-beta signaling, oxidative stress, innate immunity and inflammation, cholesterol homeostasis, and lipid-raft perturbation pathways were implicated Fehlbaum-Beurdeley et al, 2010 10 autoantibody biomarkers can differentiate Alzheimer’s disease sera Nagele et al, 2011 An immunosignature derived from thousands or randomly synthesised peptides is able to accurately discriminate Alzheimer’s disease Restrepo et al, 2011 An algorithm derived from a biomarker risk score, clinical lab (glucose, triglycerides, total cholesterol, homocysteine), and demographic (age, gender, education, APOE*E4 status) data O’Bryant et al, 2011. Paul, Minnesota; Beth Israel Deaconess Medical Center in Boston, Massachusetts; the University of Kansas Hospital and Mid America Heart Institute, both in Kansas City, Missouri; and Good Samaritan Hospital in Los Angeles, California. The eye receives the information of what you are reading on this page, sends it back into the thalamus and into the visual cortex on the frontal lobe, where the information is interpreted and you are finally able to understand what you are reading; all of this in the span of less than a second. Now researchers are finding that common infections also may have an effect on memory as well as other cognitive issues, such as mental processing, abstract thinking, planning as well as reasoning. Importantly dysregulation of this arm of the network results in uncontrolled replication in the nervous system and death despite immune competency. Novel types of frontotemporal lobar degeneration: beyond tau and TDP-43.
Revealing networks targeted by HSV-1 ncRNAs with in vivo gain-of-function studies

The 3C Study is also supported by the Caisse Nationale Maladie des Travailleurs Salarie s, Direction Ge ne rale de la Sante , Mutuelle Ge ne rale de l’Education Nationale, Institut de la Longe vite , Regional Governments of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research – INSERM Programme ”Cohortes et collections de donne es biologiques”. These mutants display a >100-fold reduction in virulence, and when co-infected even quench the virulence of highly neurovirulent HSV-1 strain McKrae and HSV-2 strain 186. In one study, which is based on the Betula project, a study on ageing, memory and dementia, the researchers show that a reactivated herpes infection doubled the risk of developing Alzheimer’s disease. We hypothesize that the extreme phenotypes displayed are the result of dysregulated riboregulator expression and that they will permit us to deduced the normal targets of the effector molecules. In this R21 application we propose to identify the molecular networks perturbed by the riboregulators(s), determine its primary targets and identify of the riboregulator itself (likely miR-H6) and characterize its normal pattern of expression. Herpes simplex virus infects the majority of people in the USA and remains a significant health threat. Diseases associated with virus recurrence include blindness, fatal encephalitis, and increased risk for HIV, dementia, heart disease, and diabetes.

There is no vaccine, and the reservoir of virus latent in the nervous system cannot be eliminated. Understanding the viral and host mechanisms the regulate latency and recurrence will lead directly to improved vaccines that do not reactivate, and may lead to novel and improved antiviral therapies.

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