Evaluating The Kinetics Of Proinflammatory Immune Responses To Simian Immunodeficiency Virus Infection In Rhesus Macaques By Transcrptional Analysis

Evaluating the Kinetics of Proinflammatory Immune Responses to Simian Immunodeficiency Virus Infection in Rhesus Macaques by Transcrptional Analysis

Understanding the host response immediately following mucosal HIV-1 infection will be pivotal in determining whether the immune response induced by a vaccine will successfully sense and control viral replication. In order for effective vaccine strategies and modalities to be developed, these earliest immunological events must be fully assessed in a non-biased manner. Nonhuman primates (NHP), specifically Rhesus macaques (RM), serve as a model to investigate the immunological landscape immediately post-challenge and to define the spatiotemporal path of simian immunodeficiency virus (SIV). SIV infection of RM serves as a model of human HIV infection as it recapitulates many of the virological, immunological, and pathological features of HIV infection vii in the human host. In this thesis I will test the hypothesis whether transcriptional analysis will allow a sensitive measure of the early innate immune responses that accompany detection of the SIV virus in the periphery. I have determined that an early inflammatory profile arises early in tissues proximal to the challenge site that precedes widespread immune activation and the systemic antiviral interferon response. This study defines in detail the spatiotemporal relationship between virus and host immune response and may be a valuable resource in guiding future vaccine design strategies.

Immune and intrinsic correlates of protection in Rhesus macaques immunised against Simian Immunodeficiency Virus

Patterns of Cytokine Gene Expression in Lymphoid Tissues of Normal and Simian Immunodeficiency Virus (SIV)-infected Rhesus Macaques