Murine Model of Cytomegalovirus Latency and Reactivation: The Silencing/Desilencing and Immune Sensing Hypothesis
Christian O. Simon, Christof K. Seckert, Natascha K.A. Grzimek, and Matthias J. Reddehase
from: Cytomegaloviruses: Molecular Biology and Immunology (Edited by: Matthias J. Reddehase). Caister Academic Press, U.K. (2006)
Abstract
Productive CMV infection is resolved and fatal disease is prevented by a functional immune system, primarily by CD8 T cells, but a magic hat appears to preserve the virus from being eliminated. The viral genome persists for the lifetime of its host in the presence of a fully developed, protective antiviral immune memory. This phenomenon, - known as virus latency -, is a hallmark that CMVs share with all other members of the herpesvirus family. Invisibility for CD8 T cells implies the absence of peptide presentation through MHC class I molecules. Theoretically, this could be accomplished by hiding in cells that are negative or at least low for class I expression, by actively downmodulating the MHC class-I pathway of antigen processing and presentation or, most easily, by gene expression quiescence. Yet, persistence and even accumulation of activated effector-memory CD8 T cells in latently infected host tissues in concert with complete transcriptional reactivation and virus recurrence after immunodepletion rather suggest that the immune system is permanently engaged in scanning latently infected cells for presented epitopes to detect and eliminate cells in which the virus attempts to reactivate. Here we summarize data from the murine model in support of a hypothesis that combines gene silencing/desilencing and immune sensing to explain CMV latency and reactivation read more ...
