Murine model of cytomegalovirus latency and reactivation.
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 establishment 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 immunoevasins, 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 a dynamic state characterized by episodes of viral gene desilencing and immune sensing of reactivated presentation of antigenic peptides at immunological checkpoints by CD8 T cells. This sensing maintains viral replicative latency by triggering antiviral effector functions that terminate the viral gene expression program before infectious viral progeny are assembled. According to the immune sensing hypothesis of latency control, immunological checkpoints are unique for each infected individual in reflection of host MHC (HLA) polymorphism and the proteome(s) of the viral variant(s) harbored in latency.
Reddehase
M J
MJ
Institute for Virology, Johannes Gutenberg-University, Obere Zahlbacher Strasse 67, Hochhaus am Augustusplatz, 55131, Mainz, Germany. Matthias.Reddehase@uni-mainz.de
Simon
C O
CO
Seckert
C K
CK
Lemmermann
N
N
Grzimek
N K A
NK
D000818:Animals; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000821:virology*; D004195:Disease Models, Animal; D051379:Mice; D014775:Virus Activation; D017735:Virus Latency