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  • Review Article
  • Published:

Herpesviruses remodel host membranes for virus egress

Key Points

  • Herpesvirus capsids containing genomic DNA assemble in the nucleus. These capsids obtain an initial envelope by budding through the inner nuclear membrane into the perinuclear space.

  • The nascent perinuclear virions then loses their envelope by fusion with the outer nuclear membrane, delivering nucleocapsids into the cytplasm. Capsids then acquire a second envelope studded with viral glycoproteins by budding into trans-Golgi network (TGN)-derived membranes.

  • Virions within the TGN-derived vesicles are then transported by exocytosis to the extracellular space.

  • In polarized epithelial cells and neurons, there is directed sorting of virus progeny toward specific cell surfaces, such as the epithelial cell–cell or neuron–epithelial cell junctions.

  • During many of these processes, herpesviruses modify cellular membranes to augment viral replication and egress, and cellular processes are exploited to promote viral secretion.

Abstract

Herpesviruses replicate their DNA and package this DNA into capsids in the nucleus. These capsids then face substantial obstacles to their release from cells. Unlike other DNA viruses, herpesviruses do not depend on disruption of nuclear and cytoplasmic membranes for their release. Enveloped particles are formed by budding through inner nuclear membranes, and then these perinuclear enveloped particles fuse with outer nuclear membranes. Unenveloped capsids in the cytoplasm are decorated with tegument proteins and then undergo secondary envelopment by budding into trans-Golgi network membranes, producing infectious particles that are released. In this Review, we describe the remodelling of host membranes that facilitates herpesvirus egress.

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Figure 1: Overview of the egress pathway of herpesviruses.
Figure 2: Electron micrographs of the steps of herpesvirus egress.
Figure 3: Primary envelopment.
Figure 4: De-envelopment.
Figure 5: Secondary envelopment.
Figure 6: Sorting of virions within host cells.

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Acknowledgements

Studies in the Baines laboratory were supported by US National Institutes of Health (NIH) grants R01 AI52341 and R01 GM50740. The work in the Johnson laboratory was supported by NIH grants R01 EY018755 and R01 AI081517. We thank T. Howard for helping to create the figures, and M. Webb for the electron microscopy images in figure 2.

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Johnson, D., Baines, J. Herpesviruses remodel host membranes for virus egress. Nat Rev Microbiol 9, 382–394 (2011). https://doi.org/10.1038/nrmicro2559

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