Biology Reference
In-Depth Information
Initiation of Cytomegalovirus Infection at ND10
G. G. Maul
Contents
Structural Observations in the First Hours After CMV Infection and Their Limits
in Interpretative Value . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
Are ND10 Really the Start Sites of CMV Transcription?. . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
Structural and Functional Aspects of IE1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
IE1 Counteracts the Host Cell's Silencing Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
Effect of ND10-Associated Proteins on CMV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
PML . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
Daxx . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
ATRX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
Sp100 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
HDAC. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128
Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
Abstract
As a large double-stranded DNA virus, CMV replicates in the nucleus, a
highly structured environment. Diffusional and solid phases exist as interdependent
sets of interactions between many components that determine either replicative suc-
cess of an infecting virus or the defensive success of the host cell. In their extremes,
cell death may be part of the lytic release of viral particles, or, in defense terms, the
ultimate sacrifice preventing virus release. Between these extremes exists an evolu-
tionarily derived standoff between virus and cell. Exogenous shifts in homeostasis
can disturb this balance, diminishing the cell's defensive powers and reactivating
the silenced viral genome. Many of the solid-phase aspects of this process can be
seen in situ and analyzed. This review evaluates structural information derived from
CMV-infected cells in situ at very early times of infection and the conceptional
advances derived from them, mostly centering on the major immediate early gene
products, specifically IE1. A scientific basis for considering the major immediate
early proteins as potential targets in suppressing CMV disease is discussed.
G.G. Maul
The Wistar Institute , 3601 Spruce Street, Philadelphia , PA 19014 , USA
maul@wistar.org
