Immune Sensing of Latent Cytomegalovirus Reactivation and its Possible Impact on Immune Senescence
M.J. Reddehase
Institute for Virology, Johannes Gutenberg-University, Obere Zahlbacher Str. 67 (Hochhaus am Augustusplatz), 55131 Mainz, Germany
Productive cytomegalovirus (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 could be accomplished by hiding in cell types 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 viral gene silencing. 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 I will 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. Recurring restimulation of memory CD8 T cells by epitopes
presented during viral latency can explain the expansion of the pool of
CMV-specific CD8 T cells with ageing, and the associated high number of
cell divisions of each clonotypic memory cell may directly relate to
the phenomenon of immune senescence.
Key words:
Cytomegalovirus, Latency, Memory Cells, Silencing, Reactivation
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