We will study the effects of simulated microgravity and ionizing radiation on the complex process of virus reactivation that is intimately associated with the way cells respond to external stress.…

We will study the effects of simulated microgravity and ionizing radiation on the complex process of virus reactivation that is intimately associated with the way cells respond to external stress. Tools to evaluate the effects of radiation and simulated microgravity will include: both viral and cellular gene expression, viral infectivity and viral titer, and DNA methylation. In addition, this proposal aims to increase our understanding of mechanisms of EBV reactivation and therefore, has the potential to discover new therapeutic targets for diseases caused in the general population by EBV. Therefore this proposal appropriately addresses `b.1. Ground-based research designed to lead to space flight; 2. Cell biology and microbiology: this section of the NRA solicits novel ground-based experiments that use cell cultures, tissue cultures, microbiological organisms or small invertebrate organisms to elucidate the basic mechanisms living systems use to respond to changes in gravity, i.e., how are changes sensed and transduced to alter gene expression and the structure and function of the musculoskeletal system.the reactivation of all herpesviruses is known to involve 2 components or stages: the initial initiating molecular events that cause reactivation of the latent genomes to progress to the production of reactivating virus, and then the propagation of these reactivating viruses to produce clinical disease. The second part of this process undoubtedly involves overcoming components of the acquired immune response if clinical disease is to result. In order to understand reactivation from a mechanistic point of view, these two processes need to be examined independently. In the proposed studies, we will be focusing only on the initial events that microgravity and ionizing radiation initiate in latent cells to induce the first stage of (molecular) reactivation. EBV reactivation may not be completely homologous to VZV and CMV reactivation. The important point here though is that by focusing on EBV, which has a well-established cell culture system of latency, we can study the mechanistic effects of microgravity and ionizing radiation in inducing EBV reactivation. This alone will provide critical and important information regarding the effects of these inducers on EBV reactivation in humans. Clearly, after these molecular events are established in EBV, possible parallel mechanisms in VZV and CMV can be investigated in future studies.