This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Dengue virus is the biggest new epidemic in America and Asia. The new cases and more severe hemorrhagic cases are increasing due to the spread of Aedes aegypti mosquito as well as for the lower socio-economical conditions of the people of such regions of the world. The increase in severity is linked to secondary infections of more than one of the four types of viruses, DEN 1,2,3 and 4. We propose to use Rhesus monkeys to provide a sets of tests to better monitor the infection of dengue virus and to better understand the pathophysiology of the disease. We will determine viremia and use new markers of dengue virus infection including sub-populations of blood cells over time. In addition, we will manipulate the immune system of the animals in such way that clearance of the virus and numbers of circulating blood cells can be investigated. The introduction of new infection markers that are potentially more sensitive than the detection of virus RNA or virus antigen NS1 in blood would help us validate such markers for their future use in patients, and will contribute to a better understanding of the progression of the disease in vivo. By providing clinical parameters over time during the infection process in the Rhesus model, time-related changes of the absolute numbers of circulating blood cells, viremia, coagulation studies and liver and muscle damage of each animal, we will be able to provide a complete clinical model of dengue disease. This year, when massive amounts of children will be vaccinated with a commercial vaccine for dengue, this research will provide the battery of tests that can eventually be used to monitor immunity and hemorrhagic/inflammatory responses.
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