Pathophysiology of Viruses and Radiation
Armed Forces Radiobiology Research Institute
Our goal is to understand how the pathobiological effects of radiation and viruses singly and in combination alter the function of host defenses with emphasis on innate immune system processes. Our experiments primarily use macrophage and epithelial cell lines, and the influenza virus, a major worldwide cause of morbidity and mortality. Experimental approaches are molecular, immunobiological, and cell biological. Responses by macrophages to diverse pathobiological challenges include changes in their activation state, secretion of inflammatory cytokines, and their death by apoptosis. Epithelial cells are the normal host for influenza virus replication with infection also causing secretion of immunomodulators and apoptosis. Innate immune system cells are relatively insensitive to radiation damage, and radiation effects in these cell types appear to primarily be modulation of the host cell responses to infection. Although radiation and viruses are likely to involve both common and unique pathobiological processes, the specific intracellular responses, cell signaling pathways, and their relative importance and interactions are still poorly understood. A concurrent goal is to identify and define the action of drugs and biological response modifiers including immunomodulators, which can decrease the harmful effects of radiation, the combined virus-radiation injury, and the inflammatory response.