Simpson, Richard J.LaVoy, Emily C.2021-07-242021-07-24August 2022020-08August 202Portions of this document appear in: Rooney BV, Crucian BE, Pierson DL, Laudenslager ML and Mehta SK (2019) Herpes Virus Reactivation in Astronauts During Spaceflight and Its Application on Earth. Front. Microbiol. 10:16. doi: 10.3389/fmicb.2019.00016https://hdl.handle.net/10657/7914Cytomegalovirus (CMV) is a common beta-herpes-virus that is oftentimes shed in the body fluids of astronauts during short space shuttle (10-16 days) and longer International Space Station (≥180 days) missions. The presence of viral DNA in body fluids indicates reactivation from latency, as well as replication, and can be observed as early as 10 days before launch. The viral load, or copies of viral DNA, continue to rise throughout the spaceflight endeavor. This is problematic for astronauts tasked for extended missions such as to the Moon, Mars and beyond during future exploration-class missions. Current anti-viral treatments are only moderately effective and have significant toxicities further compounding the problem, and there is no treatment for latent CMV. Uncontrolled CMV infections can lead to inflammation of major organs, as well as major cognitive and functional disabilities, as has been shown in immunocompromised bone marrow and solid organ transplant recipients. CMV reactivation in astronauts is further complicated by a spaceflight-induced dysregulation of the immune system where control of viral replication and expansion is impaired. NK-cells of the innate arm and T-cells of the adaptive arm of the immune system suffer cytotoxic deficits that render them incapable of suppressing and/or eliminating free virus or virally infected cells. Though many factors have been implicated in terrestrial reactivation of CMV, including stress hormones and inflammatory cytokines, the specific factors responsible for the nearly 8-fold increases in CMV viral titer observed during spaceflight have not been elucidated. The implication is that factors unique to the spaceflight environment are responsible, and this makes microgravity a prime candidate for investigation. This dissertation, therefore, sought to determine the history and prevalence of CMV reactivation during spaceflight, as well as the unique contribution of simulated microgravity (SMG), using rotating wall vessel (RWV) technology, on the in vitro CMV infection of, and replication amid, immortalized myeloid progenitor cells. Further, we sought to determine the effect of SMG on CMV virulence or its magnitude of expansion measured by the percentage of lysed fibroblast cells due to CMV infection. The outcome of this study highlights microgravity’s influence on CMV infection and reactivation.application/pdfengThe author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. UH Libraries has secured permission to reproduce any and all previously published materials contained in the work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).Microgravity, Cytomegaolvirus, Viral Reactivation2021-07-24Thesisborn digital