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Review
. 2012 Mar;40(6):2369-76.
doi: 10.1093/nar/gkr1076. Epub 2011 Nov 23.

Chromatin structure of adenovirus DNA throughout infection

Andrea N Giberson  1 , Adam R Davidson, Robin J Parks
Affiliations
Review

Chromatin structure of adenovirus DNA throughout infection

Andrea N Giberson et al. Nucleic Acids Res. 2012 Mar.

Abstract

For more than half a century, researchers have studied the basic biology of Adenovirus (Ad), unraveling the subtle, yet profound, interactions between the virus and the host. These studies have uncovered previously unknown proteins and pathways crucial for normal cell function that the virus manipulates to achieve optimal virus replication and gene expression. In the infecting virion, the viral DNA is tightly condensed in a virally encoded protamine-like protein which must be remodeled within the first few hours of infection to allow for efficient expression of virus-encoded genes and subsequent viral DNA replication. This review discusses our current knowledge of Ad DNA-protein complex within the infected cell nucleus, the cellular proteins the virus utilizes to achieve chromatinization, and how this event contributes to efficient gene expression and progression of the virus life cycle.

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Figures

Figure 1.
Figure 1.
Schematic of the adenovirus genome and virion. (A) A simplified map of the Ad5 genome showing the early genes (E1–E4) and the region from which the major late transcript is produced (the extensively spliced L1–L5 transcripts produced from alternative splicing of the major late transcript are not shown). The relative position of pIX, VA RNA I and II and IVa2 are indicated. Also shown are the viral inverted terminal repeats (ITR) located at each end of the genome, the viral packaging element (Ψ) located adjacent to the left ITR, and the position of the major late promoter (MLP). Please note that these features are not drawn to scale. (B) Model of the Ad5 virion, adapted from (9), with modifications based on additional data provided by (8,10,11).
Figure 2.
Figure 2.
Adenovirus DNA chromatin structure throughout infection. In black—elements that we know. In blue and italics—speculation/areas of future research. DNA in the Ad capsid is highly condensed with core protein VII (1), along with protein V and µ (not shown). The protein VII-DNA complex transits to the nucleus (2), and undergoes remodeling to decondense the core before transcription of early genes can begin (3). Remodeling may involve loss of at least some VII. At the time when viral gene expression is first detected, histones can be found bound to the viral DNA along with VII. Histone variant H3.3 is preferentially deposited on the viral DNA, through the action of HIRA and CHD1 (4). Onset of viral DNA replication may be accompanied by a shift to deposition of H3.1 by the CAF1 complex on the DNA, as is observed for HSV1 (5). As the histone pool is depleted and the intracellular levels of newly synthesized pre-protein VII increase, there is a transition of Ad DNA association from nucleosomes to pre-protein VII, possibly mediated by TAF-III (6). The viral DNA condensed with pre-protein VII is packaged into the Ad capsid (1).
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