Two New NIH Grants Announced

Infectious Triggers In Chronic Fatigue Syndrome
Steven E. Schutzer, MD
University of Medicine and Dentistry of New Jersey – New Jersey Medical School

Funding Institute: National Institute of Allergy and Infectious Diseases
Project Start Date: March 1, 2010
Project End Date: February 29, 2012
Funding for 2010: $273,000

DESCRIPTION (provided by applicant): Chronic fatigue syndrome (CFS) is a major disabling illness of unknown etiology. It directly impacts more than four million Americans. Infectious agents have been highly suspected but none have ever been validated. Obstacles to their discovery have been lack of a broad approach that can both detect the presence of multiple microbes in a single sample and detect novel or variants of microbes. This has been further hampered because more than 99% of all microbes cannot be cultured and may go undetected. In contrast to past limitations, we will use a new approach that can surmount these obstacles. The discovery of potential pathogens in cerebrospinal fluid of CFS would be field-altering in terms of approach to the study of the disease and possible early detection, prevention and treatment. This could be the gateway step to generate new hypotheses and begin investigation into a microbe’s causal association and ways to prevent (egg vaccine) or counteract the effects of a microbial pathogen.

PUBLIC HEALTH RELEVANCE: Chronic fatigue syndrome is the major acquired disease of productive adults. The cause remains unknown. If we can uncover an infectious cause, which is suspected, diagnostics and therapies may be developed to decrease costs and suffering to the individual and the burden on our health care system and economy.

Stress Effects on Virus Protein Induced Inflammation and Sickness Behavior
Ronald Glaser, PhD
Ohio State University

Funding Institute: National Institute of Allergy and Infectious Diseases
Project Start Date: April 15, 2010
Project End Date: March 31, 2015
Funding for 2010: $700,040

DESCRIPTION (provided by applicant): Work from our laboratory has focused on the pathophysiology of Epstein-Barr virus (EBV), a gamma herpesvirus which is associated with several human malignancies including B-cell lymphoma and nasopharyngeal carcinoma. We have also explored the role that psychological stress plays in the modulation of the steady state expression of EBV early proteins and how stress could be a factor in the risk for EBV associated disease. This proposal will focus on how EBV can induce inflammation in vitro and in mice. We have explored the hypothesis that EBV-encoded early proteins can induce immune changes observed in patients infected with EBV independent of their role in viral replication. We discovered that EBV-encoded deoxyuridine triphosphate nucleotidohydrolase (dUTPase) up-regulates the production of several proinflammatory cytokines including TNF-a, IL-1, IL-6, IL-8, as well as IL-10 in macrophages. When purified EBV-encoded dUTPase was inoculated into mice the protein was capable of producing symptoms compatible with cytokine-induced sickness behavior. The data demonstrate that EBV-encoded dUTPase can induce sickness behavior in mice resulting in increased body temperature and decreased body mass and physical activity. Furthermore, there is new and extensive literature linking chronic inflammation with an increased risk for cancer. Our data provide a new perspective on how a latent herpes virus, such as EBV, when reactivated by stress or other factors, could cause immune dysregulation, the activation in NF?B in macrophages and the upregulation of proinflammatory cytokines with possible implications for EBV associated clinical symptoms and disease, including EBV associated tumors.

PUBLIC HEALTH RELEVANCE: This multidisciplinary research grant will provide new information on how stress can have an impact on the pathophysiology on herpesvirus associated diseases.

June 3, 2010