The Syrian golden hamster is highly susceptible to a variety of intracellular pathogens, and serves as an excellent model for these pathogens' corresponding human diseases. At present, the hamster is the only practical animal model for human viral hemorrhagic fever syndrome caused by arenaviruses and phlebovirus, and for human hantavirus pulmonary syndrome. Most of these viruses are highly infectious by aerosol, causing rapidly progressing symptoms with an extremely high case fatality. The potential use of these viruses as biological warfare agents is an increasing concern. Despite their severity and obvious public health importance, there is a paucity of information on the pathogenesis of these high-containment pathogens. This is in part due to the lack of adequate small animal models. Commonly used laboratory strains of mice can be persistently infected, without overt clinical and pathological changes. Recent studies have indicated that infected hamsters can closely resemble certain features of human diseases; however, their utility in disease research has been hampered because there are currently almost no hamster immunological reagents available commercially. In this application, we will take a genetic immunization approach to generate high titer rabbit antibodies specific to hamster cytokines and cell surface molecules that are known to play critical roles in innate and cell-mediated immunity. We will then apply these antibodies in hamster models of hantavirus pulmonary syndrome and yellow fever virus infection, aimed at examining whether host immune responses contribute to disease pathogenesis. This proposal represents a distinct area of investigation and should open numerous avenues for the use of hamsters in the study of pathogens that represent important bioterrorism and emerging disease threats. ? ?
