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