Interactions Between Mouse Cytomegalovirus (mCMV) and its Host as a Function of Infection Route, Age and Virus Reactivation

Abstract

A number of variables, including viral dose, route of infection, and age at infection have profound impacts on host-pathogen interactions and can exert significant influence over the outcome and severity of viral infections. 1) Viral dose can directly influence initial viral burden and subsequent replication within the host, influencing the severity of infection and magnitude of immune resources needed to limit replication 2) route of infection (whether through inhalation, ingestion, or direct contact) determines the site of viral entry and ensuing dissemination, 3) age at infection is a critical determinant of host susceptibility, with neonates and young individuals, as well as older adults, exhibiting impaired antiviral responses, rendering them more vulnerable to severe disease outcomes. As such, achieving a more complete understanding of host/pathogen interactions demands an exploration of the relative contribution of these variables independently and in tandem to the development and maintenance of immune responses. The goal of this dissertation is to present research that has taken these factors into account. Here I will highlight how these variables shape the immune response to cytomegalovirus infection from early acute infection into latency, and how the longitudinal reactivation of cytomegalovirus influences immunity over the lifespan. Each chapter of this dissertation will contain relevant background information for topics covered therein.