The overall objective of this Program Project is to understand the pathophysiology of Zika virus (ZIKV) infection in pregnancy. Three distinct, but synergistic Projects will examine different aspects of this overarching research problem. They will define the relationship between maternal viremia and risk of fetal infection and pathogenesis (Project 1), examine the impact of pre-existing immunity to dengue virus (DENV), a close relative of ZIKV, on the outcomes of ZIKV infection in pregnancy (Project 2), and determine whether antibody immunotherapy can reduce both maternal viremia and risk of fetal pathol- ogy (Project 3). Additionally, DENV- and ZIKV-naive pregnant macaques infected with ZIKV in Project 1 will serve as controls for the other Projects. Major outcome measures in all these experiments will include the level and duration of maternal ZIKV viremia and the level and dissemination of ZIKV in neo- natal tissues. Therefore, to allow for valid and robust comparisons across Projects, this P01 requires a well-characterized large-scale ZIKV challenge stock and validated measurements of ZIKV in biological specimens. Project 2 will similarly require a defined stock of DENV and validated assays to track DENV replication. The Virology Core will support all 3 Projects by providing these virus stocks and assays, as well as technical expertise in the interpretation of data. We will accomplish this through 4 specific aims:
Specific Aim 1 : Provide a characterized stock of ZIKV to each Project Specific Aim 2: Provide a characterized DENV-2 stock for Project 2 Specific Aim 3: Measure ZIKV burdens in body fluids and tissues for each Project Specific Aim 4: Measure DENV burdens in blood for Project 2 The Virology Core will be led by Dr. Thomas Friedrich, an expert in nonhuman primate virology and molecular diagnostics, who is also co-Investigator on Project 1. Dr. Matthew Aliota, junior Lead on Project 2, will serve as co-Investigator in the Virology Core, lending his expertise in flavivirus biology. The Virology Core will thus be tightly integrated with the entire P01.
