Biology Reference
In-Depth Information
Murine Model of Cytomegalovirus Latency
and Reactivation
M. J. Reddehase (
ΓΌ
), C. O. Simon , C. K. Seckert , N. Lemmermann ,
N. K. A. Grzimek
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 316
Definitions and Caveats: The Difference Between Latency and Persistence . . . . . . . . . . . . . 317
Latent Viral Genome Load Defining the Risk of Recurrence. . . . . . . . . . . . . . . . . . . . . . . . . 320
Bidirectional Gene Pair Architecture of the Regulatory Major Immediate Early Locus . . . . 321
Stochastic Desilencing of the Major Immediate Early Locus During Latency . . . . . . . . . . . 323
Extrinsic Signals Triggering Transcriptional Reactivation and Recurrence . . . . . . . . . . . . . . 323
Role of Viral Chromatin Remodeling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
Dynamic Control of Latency at Immunological Checkpoints:
The Immune Sensing Hypothesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
Concluding Thoughts and Perspectives. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 328
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 328
Abstract
Efficient resolution of acute cytopathogenic cytomegalovirus infection
through innate and adaptive host immune mechanisms is followed by lifelong
maintenance of the viral genome in host tissues in a state of
replicative latency
,
which is interrupted by episodes of virus reactivation for transmission. The estab-
lishment of latency is the result of aeons of co-evolution of cytomegaloviruses and
their respective host species. Genetic adaptation of a particular cytomegalovirus to
its specific host is reflected by
private
gene families not found in other members
of the cytomegalovirus group, whereas basic functions of the viral replicative cycle
are encoded by
public
gene families shared between different cytomegaloviruses or
even with herpesviruses in general. Private genes include genes coding for immu-
noevasins, a group of glycoproteins specifically dedicated to dampen recognition
by the host's innate and adaptive immune surveillance to protect the virus against
elimination. Recent data in the mouse model of cytomegalovirus latency have
indicated that viral replicative latency established in the immunocompetent host is
M.J. Reddehase
Institute for Virology , Johannes Gutenberg-University, Obere Zahlbacher Strasse 67,
Hochhaus am Augustusplatz, 55131 , Mainz , Germany
Matthias.Reddehase@uni-mainz.de
