Biology Reference
In-Depth Information
a dynamic state characterized by episodes of viral gene desilencing and immune
sensing of reactivated presentation of antigenic peptides at immunological check-
points 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 hypoth-
esis 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.
Introduction
Cytomegalovirus (CMV) disease is an accident for both the virus and its host, and
occurs only if the intricate balance between them is disrupted in an immunologi-
cally immature or immunocompromised individual. Disease is obviously harmful
for the host, but self-limiting replication by lethal infection of the host was appar-
ently also not a successful survival strategy in the evolutionary selection of virus
strains, at least not for the members of the herpesvirus family, including the
CMVs. The establishment of latent infection after resolution of the acute infection
by the host's innate and adaptive immune mechanisms is a hallmark of herpesvirus
biology. Resolution of acute infection implies that productively infected cells are
recognized by cells of the immune system, resulting in an interruption of the
viral productive replication cycle by cytolytic or noncytolytic immune effector
mechanisms. Ideally, this occurs at a stage prior to completion of the replicative
cycle and to virion exit. On the other hand, establishment of a latent infection
implies that the virus escapes elimination through mechanisms of immune
evasion, which may be manifold.
CMVs are host-specific and the adaptation to their respective host species
appears to be particularly highly evolved, as is suggested by a very significant
number of
private
genes not shared between different species of CMVs. In the case
of murine CMV (mCMV), the nomenclature introduced by Rawlinson and
colleagues (1996), who have greatly expedited the field by sequencing the Smith
strain, is instructive, as mCMV's private genes are marked by lowercase letter “m”,
whereas genes with homology to genes of human CMV (hCMV) are marked by
capital letter “M”. As a rule of thumb, we expect that private genes are
host
adaptation genes
, and, indeed, viral open reading frames (ORFs) encoding
proteins involved in the modulation of the murine host's innate and adaptive
immune surveillance usually belong to the group of private genes. For most genes
of this category, however, the function is still unknown; moreover, most of them
appear to be dispensable for virus replication in cell culture (Brune et al. 2006).
It is predictable that for many of the private genes a function will be revealed only
by in vivo studies, and a great deal of scientific intuition and creativity will be
necessary to design the proper experiments. In our view, every viral gene has its
role in virus biology, the problem only is to find it! An intriguing example presenting
