Infection-induced chromatin modifications facilitate translocation of herpes simplex virus capsids to the inner nuclear membrane

PLoS Pathog. 2021 Dec 15;17(12):e1010132. doi: 10.1371/journal.ppat.1010132. eCollection 2021 Dec.

Abstract

Herpes simplex virus capsids are assembled and packaged in the nucleus and move by diffusion through the nucleoplasm to the nuclear envelope for egress. Analyzing their motion provides conclusions not only on capsid transport but also on the properties of the nuclear environment during infection. We utilized live-cell imaging and single-particle tracking to characterize capsid motion relative to the host chromatin. The data indicate that as the chromatin was marginalized toward the nuclear envelope it presented a restrictive barrier to the capsids. However, later in infection this barrier became more permissive and the probability of capsids to enter the chromatin increased. Thus, although chromatin marginalization initially restricted capsid transport to the nuclear envelope, a structural reorganization of the chromatin counteracted that to promote capsid transport later. Analyses of capsid motion revealed that it was subdiffusive, and that the diffusion coefficients were lower in the chromatin than in regions lacking chromatin. In addition, the diffusion coefficient in both regions increased during infection. Throughout the infection, the capsids were never enriched at the nuclear envelope, which suggests that instead of nuclear export the transport through the chromatin is the rate-limiting step for the nuclear egress of capsids. This provides motivation for further studies by validating the importance of intranuclear transport to the life cycle of HSV-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport, Active / physiology*
  • Capsid / metabolism*
  • Chlorocebus aethiops
  • Chromatin / metabolism*
  • Herpes Simplex
  • Nuclear Envelope / metabolism*
  • Simplexvirus / metabolism*
  • Vero Cells
  • Virus Replication / physiology

Substances

  • Chromatin

Grants and funding

This work was financed by the Jane and Aatos Erkko Foundation (MVR); Academy of Finland under the award number 330896 (MVR); European Union’s Horizon 2020 research and innovation programme under grant agreement No 101017116, project CoCID (Compact Cell-Imaging Device, MVR); the Graduate School of the University of Jyvaskyla (SM). JBB is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy – EXC 2155 – project number 390874280. FF is holding a graduate student fellowship by the Studienstiftung des deutschen Volkes. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.