Biology Reference
In-Depth Information
constituents of the viral envelope, are delivered to the cellular membrane immediately
after fusion of envelope and membrane at the initial stage of infection. Upon
this rapid delivery, modulation of intracellular processes may take place even
before the immediate early stage of CMV infection commences. Interestingly,
it was shown that HCMV US28-expressing cells were able to enhance the
transcriptional activities regulated by the HCMV major immediate early promoter
via the p38/MAPK and NFk-B pathways (Boomker et al. 2006a). This observation
supports a role for virion-borne vGPCR delivery for preimmediate early
infection events.
Perspectives
The vCKs and vGPCRs described in this chapter are the result of an ever-continuing
arms race between cytomegaloviruses and the host organism. The roles of the
UL128-, UL146- and UL147-encoded vCKs will likely remain uncertain until
the phenotypes of relevant deletion mutant CMVs are examined in vivo. Since
UL33- and UL78-like genes are conserved in rodent CMV species, their contribution
to viral dissemination and replication have been well established in vivo.
Interestingly, a pantheon of phenomena has been attributed to HCMV US28.
Similar to the vCKs, more in vivo work needs to be done to determine how these
phenomena benefit CMV growth and survival in the host. CCMV is the most appropriate
model virus to address these questions.
Most existing antiviral agents against CMV disease target the viral replication
cycle. vCKs and vGPCRs are interesting targets in the development of a new class
of antiviral agents, such as synthetic small molecule GPCR ligands and chemokine
antagonists and inverse agonists. These agents could inhibit viral reactivation or
dissemination rather than replication, thereby increasing the range of available
drugs and their effectiveness against CMV disease.
References
Adler B, Scrivano L, Ruzcics Z, Rupp B, Sinzger C, Koszinowski U (2006) Role of human cytome-
galovirus UL131A in cell type-specific virus entry and release. J Gen Virol 87:2451-2460
Ahuja SK, Murphy PM (1993) Molecular piracy of mammalian interleukin-8 receptor type B by
herpesvirus saimiri. J Biol Chem 268:20691-20694
Akter P, Cunningham C, McSharry BP, Dolan A, Addison C, Dargan DJ, Hassan-Walker AF,
Emery VC, Griffiths PD, Wilkinson GW, Davison AJ. (2003) Two novel spliced genes in
human cytomegalovirus. J Gen Virol 84:1117-1122
Arav-Boger R, Zong JC, Foster CB (2005) Loss of linkage disequilibrium and accelerated protein
divergence in duplicated cytomegalovirus chemokine genes. Virus Genes 31:65-72
Arav-Boger R, Foster CB, Zong JC, Pass RF (2006) Human cytomegalovirus-encoded alpha -chemokines
exhibit high sequence variability in congenitally infected newborns. J Infect Dis 193:788-791
