title: Characterization of Epstein-Barr virus reactivation in a modeled spaceflight system.
abstract: Epstein-Barr virus (EBV) is the causative agent of mononucleosis and is also associated with several malignancies, including Burkitt's lymphoma, Hodgkin's lymphoma, and nasopharyngeal carcinoma, among others. EBV reactivates during spaceflight, with EBV shedding in saliva increasing to levels ten times those observed pre-and post-flight. Although stress has been shown to increase reactivation of EBV, other factors such as radiation and microgravity have been hypothesized to contribute to reactivation in space. We used a modeled spaceflight environment to evaluate the influence of radiation and microgravity on EBV reactivation. BJAB (EBV-negative) and Raji (EBV-positive) cell lines were assessed for viability/apoptosis, viral antigen and reactive oxygen species expression, and DNA damage and repair. EBV-infected cells did not experience decreased viability and increased apoptosis due to modeled spaceflight, whereas an EBV-negative cell line did, suggesting that EBV infection provided protection against apoptosis and cell death. Radiation was the major contributor to EBV ZEBRA upregulation. Combining modeled microgravity and radiation increased DNA damage and reactive oxygen species while modeled microgravity alone decreased DNA repair in Raji cells. Additionally, EBV-infected cells had increased DNA damage compared to EBV-negative cells. Since EBV-infected cells do not undergo apoptosis as readily as uninfected cells, it is possible that virus-infected cells in EBV seropositive individuals may have an increased risk to accumulate DNA damage during spaceflight. More studies are warranted to investigate this possibility.
authors.affiliation: Departments of Preventive Medicine, Community Health, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Alaina A
authors.initials: AA
authors.lastname: Brinley
authors.forename: Corey A
authors.initials: CA
authors.lastname: Theriot
authors.forename: Mayra
authors.initials: M
authors.lastname: Nelman-Gonzalez
authors.forename: Brian
authors.initials: B
authors.lastname: Crucian
authors.forename: Raymond P
authors.initials: RP
authors.lastname: Stowe
authors.forename: Alan D T
authors.initials: AD
authors.lastname: Barrett
authors.forename: Duane L
authors.initials: DL
authors.lastname: Pierson
mesh_terms: D000956:Antigens, Viral / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis; D002051:Burkitt Lymphoma / Q000821:virology; D045744:Cell Line, Tumor; D002470:Cell Survival; D004249:DNA Damage; D004260:DNA Repair; D020031:Epstein-Barr Virus Infections / Q000821:virology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism; D013026:Space Flight; D015854:Up-Regulation; D014764:Viral Proteins / Q000378:metabolism; D014775:Virus Activation / Q000528:radiation effects; D017735:Virus Latency; D018474:Weightlessness Simulation
chemical_list: D000956:Antigens, Viral; C083278:BHRF1 protein, Human herpesvirus 4; D017382:Reactive Oxygen Species; D014764:Viral Proteins