The Effect of Modeled Microgravity and Radiation on Epstein-Barr Virus in a Modeled Spaceflight System

Epstein-Barr virus (EBV) is the causative agent of mononucleosis and is also associated with several malignancies, including Burkitt’s lymphoma, Hodgkin’s lymphoma, nasopharyngeal carcinoma, and post-transplant lymphoproliferative disorder, among others. EBV is known to reactivate during spaceflight, increasing to levels ten times those observed pre-and post-flight. Although stress has been shown to increase reactivation of EBV, other factors, including radiation and microgravity, are thought to contribute to reactivation in space. This research used a modeled spaceflight environment to evaluate the influence of radiation and microgravity on EBV reactivation. The first phase of the project assessed how the cell cycle, cellular viability, apoptosis, and morphology were affected by EBV lytic activity and the modeled spaceflight environment. It was determined that EBV reactivated in response to radiation, and modeled microgravity affected the cellular environment to make it more conducive to viral replication. EBV-infected cells did not experience decreased viability and increased apoptosis whereas an EBV-negative cell line did, suggesting that EBV infection provided protection against apoptosis and cell death. This study also assessed DNA damage due to radiation, modeled microgravity, and the combination of the two factors. Combining modeled microgravity and radiation increased DNA damage and reactive oxygen species (ROS), and also decreased DNA repair. Additionally, EBV-infected cells had increased DNA damage compared to EBV-negative cells supporting previous non-spaceflight literature that found that EBV increases genomic instability. These studies suggest that individuals infected by EBV (>90% of humans) may have an increased risk for DNA damage to accumulate during spaceflight since EBV-infected cells do not undergo apoptosis and cell death as readily as uninfected cells. Overall, increased viral activation, increased DNA damage, decreased DNA repair, increased cellular proliferation, and increased ROS were found in the modeled spaceflight environment. The combination of all of these factors may increase the risk for malignancy due to long-duration spaceflight exposure. Therefore, the conclusion of this research is that development of countermeasures to minimize the effects of long exposures to radiation and microgravity should be included in future studies, concurrent with research on other physiological systems related to interplanetary transit missions.

Name thesis:degree_name

Population Health Sciences (Doctoral)

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Virology/Space Life Sciences

Grantor

The University of Texas Medical Branch at Galveston

Author dc:creator

• Brinley, Alaina 1985-

Advisor dc:contributor.advisor

• Barrett, Alan D

Committee members dc:contributor.committeemember

• Pierson, Duane L
• Rudkin, Laura
• Niesel, David
• Stowe, Raymond

• Epstein-Barr virus
• EBV
• radiation
• modeled microgravity
• bioreactor

Handle dc:identifier.uri

http://hdl.handle.net/2152.3/833

OAI identifier oai:identifier

oai:utmb-ir.tdl.org:2152.3/833