Abstract
Herpes simplex virus (HSV) is a neurotropic virus that establishes lifelong latent infection in human ganglion sensory neurons. This unique life cycle necessitates an intimate relation between the host defenses and virus counteractions over the long course of infection. Two important aspects of host anti-viral defense, nuclear substructure restriction and epigenetic chromatin regulation, have been intensively studied in the recent years. Upon viral DNA entering the nucleus, components of discrete nuclear bodies termed nuclear domain 10 (ND10), converge at viral DNA and place restrictions on viral gene expression. Meanwhile the infected cell mobilizes its histones and histone-associated repressors to force the viral DNA into nucleosome-like structures and also represses viral transcription. Both anti-viral strategies are negated by various HSV countermeasures. One HSV gene transactivator, infected cell protein 0 (ICP0), is a key player in antagonizing both the ND10 restriction and chromatin repression. On one hand, ICP0 uses its E3 ubiquitin ligase activity to target major ND10 components for proteasome-dependent degradation and thereafter disrupts the ND10 nuclear bodies. On the other hand, ICP0 participates in de-repressing the HSV chromatin by changing histone composition or modification and therefore activates viral transcription. Involvement of a single viral protein in two seemingly different pathways suggests that there is coordination in host anti-viral defense mechanisms and also cooperation in viral counteraction strategies. In this review, we summarize recent advances in understanding the role of chromatin regulation and ND10 dynamics in both lytic and latent HSV infection. We focus on the new observations showing that ND10 nuclear bodies play a critical role in cellular chromatin regulation. We intend to find the connections between the two major anti-viral defense pathways, chromatin remodeling and ND10 structure, in order to achieve a better understanding of how host orchestrates a concerted defense and how HSV adapts with and overcomes the host immunity.
Highlights
Herpes simplex virus (HSV) is a member of family Herpesviridae, genus Simplexvirus
The second observation that chromatin formation represses Herpes Simplex Virus-1 (HSV-1) expression is the fact that inhibitors targeting chromatin deactivating enzymes, such as histone deacetylases (HDACs) [16, 17], promoted viral gene expression and DNA replication for a recombinant HSV-1 containing a growth defect [18], indicating the significance of the reversal of histone deacetylation in lytic HSV-1 infection
In latent infection HSV genome DNA is clearly packed into chromatin and HSV genes are fully regulated through the host epigenetic machineries, the processes of how chromatinization is initiated to establish latency and how chromatin repression is released to reactivate from latency are largely unknown
Summary
Herpes simplex virus (HSV) is a member of family Herpesviridae, genus Simplexvirus. After the primary infection at oral, genital or ocular mucosa, HSV establishes latency in ganglion sensory neurons. Chromatin-regulated gene repressions and nuclear domain 10 (ND10)-associated anti-viral restrictions are two
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