title: Stress-associated changes in the steady-state expression of latent Epstein-Barr virus: implications for chronic fatigue syndrome and cancer.
abstract: Antibodies to several Epstein-Barr virus (EBV)-encoded enzymes are observed in patients with different EBV-associated diseases. The reason for these antibody patterns and the role these proteins might play in the pathophysiology of disease, separate from their role in virus replication, is unknown. In this series of studies, we found that purified EBV deoxyuridine triphosphate nucleotidohydrolase (dUTPase) can inhibit the replication of human peripheral blood mononuclear cells in vitro and upregulate the production of TNF-alpha, IL-1beta, IL-6, IL-8, and IL-10. It also enhanced the ability of natural killer cells to lyse target cells. The EBV dUTPase also significantly inhibited the replication of mitogen-stimulated lymphocytes and the synthesis of IFN-gamma by cells isolated from lymph nodes and spleens obtained from mice inoculated with the protein. It also produced sickness behaviors known to be induced by some of the cytokines that were studied in the in vitro experiments. These symptoms include an increase in body temperature, a decrease in body mass and in physical activity. The data provide a new perspective on how an early nonstructural EBV-encoded protein can cause immune dysregulation and produce clinical symptoms observed in patients with chronic fatigue syndrome (CFS) separate from its role in virus replication and may serve as a new approach to help identify one of the etiological agents for CFS. The data also provide additional insight into the pathophysiology of EBV infection, inflammation, and cancer.
authors.affiliation: Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Medical Center, 333 W. 10th Avenue, Columbus, OH 43210, USA. glaser.1@osu.edu
authors.forename: Ronald
authors.initials: R
authors.lastname: Glaser
authors.forename: David A
authors.initials: DA
authors.lastname: Padgett
authors.forename: Monica L
authors.initials: ML
authors.lastname: Litsky
authors.forename: Robert A
authors.initials: RA
authors.lastname: Baiocchi
authors.forename: Eric V
authors.initials: EV
authors.lastname: Yang
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Peir-En
authors.initials: PE
authors.lastname: Yeh
authors.forename: Nancy G
authors.initials: NG
authors.lastname: Klimas
authors.forename: Gailen D
authors.initials: GD
authors.lastname: Marshall
authors.forename: Theresa
authors.initials: T
authors.lastname: Whiteside
authors.forename: Ronald
authors.initials: R
authors.lastname: Herberman
authors.forename: Janice
authors.initials: J
authors.lastname: Kiecolt-Glaser
authors.forename: Marshall V
authors.initials: MV
authors.lastname: Williams
mesh_terms: D000818:Animals; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000276:immunology*; D015673:Fatigue Syndrome, Chronic / Q000150:complications / Q000276:immunology*; D006801:Humans; D009369:Neoplasms / Q000150:complications / Q000276:immunology*; D013312:Stress, Physiological / Q000150:complications / Q000276:immunology*; D017735:Virus Latency / Q000276:immunology*