Biology Reference
In-Depth Information
Concluding Thoughts
Cytomegalovirus devotes much of its coding potential to functions required to produce
infectious progeny. Delineating the molecular composition of the mature virus
particle, the organization of its components, and the processes required to enable
its formation will provide new insights into biological assembly mechanisms and
critical virus-host interactions, and new leads for antiviral strategies.
Advances in the sensitivity of detecting and quantifying constituents of the vir-
ion have led to a more detailed inventory of its composition. However, much
remains to be discovered about how those components associate into substructures,
what processes drive their associations and dissociations, and what functions are
served by the resulting changes.
Ripe for further investigation are several new and less-well understood aspects
of how the virus particle is formed and delivers its DNA cargo to the host cell
nucleus:
1. What targets the infecting nucleocapsid to the nuclear pore and what triggers
DNA release at that destination?
2. What triggers maturational cleavage by the capsid protease, pUL80a, and what
drives elimination of the scaffolding elements from the interior of the nascent
capsid?
3. What is the function of the CMV-specific basic phosphoprotein (pUL32) that is
tightly associated with the outer surface of the capsid and might it help stabilize the
capsid to pressure from within exerted by the comparatively large CMV DNA?
4. How is the recently discovered ubiquitin-specific cysteine protease activity of
pUL48 involved in virus replication?
5. What are the mechanistic details of nuclear egress by the nucleocapsid?
6. What are the critical interactions between capsid and tegument components,
tegument constituents with themselves, and tegument constituents with
envelope?
Answers to these and related questions will speed progress toward identifying
new targets and strategies for antiviral drugs, and broaden our understanding of this
medically important class of viruses.
Acknowledgements
Electron micrographs were prepared by Donna Woods. Joe Dieter and Amy
Loveland helped me with the illustrations. Contributions of many colleagues to published and
unpublished work from our lab are gratefully acknowledged and were aided by Public Health
Service research grants AI13718 and AI032957.
References
Baines J, Poon A, Rovnak J, Roizman B (1994) The herpes virus 1 UL15 gene encodes two
proteins and is required for cleavage of genomic viral DNA. J Virol 68:8118-8124
Baxter MK, Gibson W (1997) The putative human cytomegalovirus triplex proteins, minor capsid
