Biology Reference
In-Depth Information
individual strains remained absolutely stable over time in vitro and in vivo, which
indicates that sequence drift is not a mechanism for the observed sequence hyper-
variability (Lurain et al. 2006). UL146 was found to be the more rapidly evolving
paralog (Arav-Boger et al. 2005). Despite the observed hypervariability, no specific
UL146 or UL147 genotype was associated with disease outcome in newborns with
CMV-associated congenital disorders (Arav-Boger et al. 2006; He et al. 2006).
Interestingly, a single CXC vCK-like gene (rh156.2) and two CXC vCK-like genes
(UL156 and UL157) have been identified in RhCMV and CCMV, respectively
(Table 1). While these genes share significant similarity with UL146-like genes,
they do not have counterparts in HCMV or rodent CMVs. This indicates that in
contrast to UL128-like genes, the UL146-like and UL147-like genes are rapidly
evolving in vivo. Finally, a distinct CC vCK was reported to be encoded by guinea
pig cytomegalovirus (GpCMV; Haggerty and Schleiss 2002). Both the genomic
localization and the DNA sequence of the MIP gene are unique for GpCMV. No
counterparts have been found on the genomes of other herpesviruses (Table 1).
The Role of vCKs During CMV Infection
The HCMV UL128 is functionally clustered within the UL128/UL130/UL131A
locus. Three mutant HCMV strains were generated in which any of these genes was
disrupted. Each of these strains completely lost its ability to replicate in human
umbilical cord endothelial cells, as well as its ability to transfer from one cell to
another in cultured polymorphonuclear leukocytes (PMNs) and monocytes (Hahn
et al. 2004 ). Thus, these genes appear to determine endothelial cell tropism as well
as cell-to-cell passage in vitro (Hahn et al. 2004). The mechanisms by which the
UL128, UL130 and UL131A genes govern these processes have recently been
addressed. It was suggested that the proteins encoded by the UL128/UL130/
UL131A locus might act as ligands for receptors that convey signals into endothelial
cells to facilitate intracellular transport or inactivation of innate intracellular antivi-
ral immunity (Patrone et al. 2005). Moreover, these proteins are a component of the
attachment/entry machinery, either by acting as a soluble factor or as a virion
component, permitting a viral entry pathway that differs from that used in fibroblasts
(Patrone et al. 2005). These proteins were also suggested to be involved in the final
stages of virus morphogenesis and maturation at membranes (Hahn et al. 2004), as
well as in attraction-adhesion of leukocytes to endothelial cells (Hahn et al. 2004).
Finally, UL128, UL130 (Wang and Shenk, 2005) and UL131 (Adler et al. 2006)
have been shown to be part of a complex with gH/gL in the virion and to play a
direct role in entry into epithelial and endothelial cells. The chemotactic activity of
each individual gene product of the UL131-128 locus, as well as the potential
cooperation with other viral or cellular gene signaling molecules, remains to be
elucidated. The HHV-6 counterpart of UL128, U83A, was found to encode a potent
CC chemokine capable of inducing Ca
2+
mobilization and chemotaxis in T lymphocytes
(Derwin et al. 2006). However, this provides little insight in the function of
