IMMUNOLOGICAL RESPONSE TO PRIMARY & SECONDARY INFLUENZA INFECTION IN NH PRIMATES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Influenza virus infects from 10 to 20% of the U.S. population annually, resulting in the death of approximately 36,000 people. Infection and mortality rates can rise dramatically during occasional pandemics, three of which have occurred over the last 90 years. There is growing concern that the next pandemic could arise from highly pathogenic avian influenza viruses, which have a mortality rate of over 50% in cases where the virus has been transmitted from infected birds to humans. Investigators in the Division of Functional Genomics and Infectious Disease are therefore using a nonhuman primate infection model to define influenza virus-host interactions and the innate and adaptive immune responses to infection. The goal of this project is to provide information that may lead to new antiviral therapies or improved vaccination strategies. Initial studies using the nonhuman primate model will focus on the host response to A/Yokohama/2017/03 (H3N2), a recent seasonal isolate of human influenza. An important component of these studies will be the detailed analysis of specific cell types isolated from the blood and lymph nodes of infected animals. Experiments performed during the current reporting period have focused on establishing the techniques and parameters for sorting cells by flow cytometry and for optimizing the timing and methods for harvesting RNA and protein from isolated cells for subsequent analysis of cellular gene expression and protein abundance profiles. With this information in hand, two groups of animals will be used in initial studies; one group to evaluate the response to a primary infection, and a second group to evaluate the response to a secondary infection initiated 42 days later. This strategy will provide information regarding the molecular mechanisms underlying innate immune responses and the character and degree of protection (adaptive immunity) provided by previous exposure to the virus.