skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Herpes simplex virus 1 induces egress channels through marginalized host chromatin

Abstract

Lytic infection with herpes simplex virus type 1 (HSV-1) induces profound modification of the cell nucleus including formation of a viral replication compartment and chromatin marginalization into the nuclear periphery. Here, we used three-dimensional soft X-ray tomography, combined with cryogenic fluorescence, confocal and electron microscopy, to analyse the transformation of peripheral chromatin during HSV-1 infection. Our data showed an increased presence of low-density gaps in the marginalized chromatin at late infection. Advanced data analysis indicated the formation of virus-nucleocapsid-sized (or wider) channels extending through the compacted chromatin of the host. Importantly, confocal and electron microscopy analysis showed that these gaps frequently contained viral nucleocapsids. Our results demonstrated that HSV-1 infection induces the formation of channels penetrating the compacted layer of cellular chromatin and allowing for the passage of progeny viruses to the nuclear envelope, their site of nuclear egress.

Authors:
 [1];  [2];  [1];  [3];  [2];  [4];  [5];  [6];  [4];  [7];  [2]
  1. Univ. of Jyvaskyla (Finland). Dept. of Physics and Nanoscience Center
  2. Univ. of Jyvaskyla (Finland). Dept. of Biological and Environmental Science and Nanoscience Center
  3. Univ. of California, San Francisco, CA (United States). Dept. of Anatomy; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  4. Univ. of Turku (Finland)
  5. International Center for Research in Infectiology, Lyon (France); Ecole Normale Superieure, Lyon (France); Univ. of Lyon (France). LabEx Ecofect
  6. Univ. of Jyvaskyla (Finland). Dept. of Physics and Nanoscience Center; ITMO uUniv., St. Petersburg (Russia)
  7. Univ. of California, San Francisco, CA (United States). Dept. of Anatomy; Univ. of Turku (Finland)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
OSTI Identifier:
1414761
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 6; Journal Issue: 1; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; herpes virus; nuclear organization

Citation Formats

Myllys, Markko, Ruokolainen, Visa, Aho, Vesa, Smith, Elizabeth A., Hakanen, Satu, Peri, Piritta, Salvetti, Anna, Timonen, Jussi, Hukkanen, Veijo, Larabell, Carolyn A., and Vihinen-Ranta, Maija. Herpes simplex virus 1 induces egress channels through marginalized host chromatin. United States: N. p., 2016. Web. doi:10.1038/srep28844.
Myllys, Markko, Ruokolainen, Visa, Aho, Vesa, Smith, Elizabeth A., Hakanen, Satu, Peri, Piritta, Salvetti, Anna, Timonen, Jussi, Hukkanen, Veijo, Larabell, Carolyn A., & Vihinen-Ranta, Maija. Herpes simplex virus 1 induces egress channels through marginalized host chromatin. United States. doi:10.1038/srep28844.
Myllys, Markko, Ruokolainen, Visa, Aho, Vesa, Smith, Elizabeth A., Hakanen, Satu, Peri, Piritta, Salvetti, Anna, Timonen, Jussi, Hukkanen, Veijo, Larabell, Carolyn A., and Vihinen-Ranta, Maija. Tue . "Herpes simplex virus 1 induces egress channels through marginalized host chromatin". United States. doi:10.1038/srep28844. https://www.osti.gov/servlets/purl/1414761.
@article{osti_1414761,
title = {Herpes simplex virus 1 induces egress channels through marginalized host chromatin},
author = {Myllys, Markko and Ruokolainen, Visa and Aho, Vesa and Smith, Elizabeth A. and Hakanen, Satu and Peri, Piritta and Salvetti, Anna and Timonen, Jussi and Hukkanen, Veijo and Larabell, Carolyn A. and Vihinen-Ranta, Maija},
abstractNote = {Lytic infection with herpes simplex virus type 1 (HSV-1) induces profound modification of the cell nucleus including formation of a viral replication compartment and chromatin marginalization into the nuclear periphery. Here, we used three-dimensional soft X-ray tomography, combined with cryogenic fluorescence, confocal and electron microscopy, to analyse the transformation of peripheral chromatin during HSV-1 infection. Our data showed an increased presence of low-density gaps in the marginalized chromatin at late infection. Advanced data analysis indicated the formation of virus-nucleocapsid-sized (or wider) channels extending through the compacted chromatin of the host. Importantly, confocal and electron microscopy analysis showed that these gaps frequently contained viral nucleocapsids. Our results demonstrated that HSV-1 infection induces the formation of channels penetrating the compacted layer of cellular chromatin and allowing for the passage of progeny viruses to the nuclear envelope, their site of nuclear egress.},
doi = {10.1038/srep28844},
journal = {Scientific Reports},
number = 1,
volume = 6,
place = {United States},
year = {2016},
month = {6}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 7 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Viruses and the nucleolus: The fatal attraction
journal, June 2014

  • Salvetti, Anna; Greco, Anna
  • Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Vol. 1842, Issue 6
  • DOI: 10.1016/j.bbadis.2013.12.010

Herpesviruses remodel host membranes for virus egress
journal, April 2011

  • Johnson, David C.; Baines, Joel D.
  • Nature Reviews Microbiology, Vol. 9, Issue 5
  • DOI: 10.1038/nrmicro2559

Herpes simplex virus 2 UL13 protein kinase disrupts nuclear lamins
journal, September 2009


Correlative cryogenic tomography of cells using light and soft x-rays
journal, August 2014


Herpes Simplex Virus Reorganizes the Cellular DNA Repair and Protein Quality Control Machinery
journal, November 2010


Herpes Simplex Virus Replication: Roles of Viral Proteins and Nucleoporins in Capsid-Nucleus Attachment
journal, December 2008

  • Copeland, A. M.; Newcomb, W. W.; Brown, J. C.
  • Journal of Virology, Vol. 83, Issue 4
  • DOI: 10.1128/JVI.01139-08

Actin in Herpesvirus Infection
journal, April 2011

  • Roberts, Kari L.; Baines, Joel D.
  • Viruses, Vol. 3, Issue 4
  • DOI: 10.3390/v3040336

Remodeling nuclear architecture allows efficient transport of herpesvirus capsids by diffusion
journal, October 2015

  • Bosse, Jens B.; Hogue, Ian B.; Feric, Marina
  • Proceedings of the National Academy of Sciences, Vol. 112, Issue 42
  • DOI: 10.1073/pnas.1513876112

Snapshots: Chromatin control of viral infection
journal, January 2013


Active intranuclear movement of herpesvirus capsids
journal, April 2005

  • Forest, Thomas; Barnard, Sandra; Baines, Joel D.
  • Nature Cell Biology, Vol. 7, Issue 4
  • DOI: 10.1038/ncb1243

X-ray tomography of whole cells
journal, October 2005

  • Le Gros, Mark A.; McDermott, Gerry; Larabell, Carolyn A.
  • Current Opinion in Structural Biology, Vol. 15, Issue 5
  • DOI: 10.1016/j.sbi.2005.08.008

Herpesviral replication compartments move and coalesce at nuclear speckles to enhance export of viral late mRNA
journal, May 2011

  • Chang, L.; Godinez, W. J.; Kim, I. -H.
  • Proceedings of the National Academy of Sciences, Vol. 108, Issue 21
  • DOI: 10.1073/pnas.1103411108

Soft X-ray microscopy analysis of cell volume and hemoglobin content in erythrocytes infected with asexual and sexual stages of Plasmodium falciparum
journal, February 2012

  • Hanssen, Eric; Knoechel, Christian; Dearnley, Megan
  • Journal of Structural Biology, Vol. 177, Issue 2
  • DOI: 10.1016/j.jsb.2011.09.003

Typing of herpes simplex virus isolates with monoclonal antibodies and by nucleic acid spot hybridization
journal, October 1985


Virus strategies for passing the nuclear envelope barrier
journal, November 2012

  • Kobiler, Oren; Drayman, Nir; Butin-Israeli, Veronika
  • Nucleus, Vol. 3, Issue 6
  • DOI: 10.4161/nucl.21979

Soft X-ray tomography and cryogenic light microscopy: the cool combination in cellular imaging
journal, November 2009

  • McDermott, Gerry; Le Gros, Mark A.; Knoechel, Christian G.
  • Trends in Cell Biology, Vol. 19, Issue 11
  • DOI: 10.1016/j.tcb.2009.08.005

Nuclear pore complex composition: a new regulator of tissue-specific and developmental functions
journal, October 2012

  • Raices, Marcela; D'Angelo, Maximiliano A.
  • Nature Reviews Molecular Cell Biology, Vol. 13, Issue 11
  • DOI: 10.1038/nrm3461

Chromatin control of herpes simplex virus lytic and latent infection
journal, March 2008

  • Knipe, David M.; Cliffe, Anna
  • Nature Reviews Microbiology, Vol. 6, Issue 3
  • DOI: 10.1038/nrmicro1794

Innate responses to small interfering RNA pools inhibiting herpes simplex virus infection in astrocytoid and epithelial cells
journal, June 2014

  • Paavilainen, Henrik; Romanovskaya, Alesia; Nygårdas, Michaela
  • Innate Immunity, Vol. 21, Issue 4
  • DOI: 10.1177/1753425914537921

Compensation for Nonuniform Resolution Using Penalized-Likelihood Reconstruction in Space-Variant Imaging Systems
journal, March 2004

  • Stayman, J. W.; Fessler, J. A.
  • IEEE Transactions on Medical Imaging, Vol. 23, Issue 3
  • DOI: 10.1109/TMI.2003.823063

Herpesvirus Entry: an Update
journal, September 2003


Imaging cellular architecture with X-rays
journal, October 2010

  • Larabell, Carolyn A.; Nugent, Keith A.
  • Current Opinion in Structural Biology, Vol. 20, Issue 5
  • DOI: 10.1016/j.sbi.2010.08.008

Micro-organization and visco-elasticity of the interphase nucleus revealed by particle nanotracking
journal, March 2004


A guided tour into subcellular colocalization analysis in light microscopy
journal, December 2006


Nuclear Egress and Envelopment of Herpes Simplex Virus Capsids Analyzed with Dual-Color Fluorescence HSV1(17+)
journal, December 2007

  • Nagel, C. -H.; Dohner, K.; Fathollahy, M.
  • Journal of Virology, Vol. 82, Issue 6
  • DOI: 10.1128/JVI.02124-07

Role for A-Type Lamins in Herpesviral DNA Targeting and Heterochromatin Modulation
journal, May 2008


Herpesviruses carrying a Brainbow cassette reveal replication and expression of limited numbers of incoming genomes
journal, December 2010

  • Kobiler, Oren; Lipman, Yaron; Therkelsen, Kate
  • Nature Communications, Vol. 1, Issue 1
  • DOI: 10.1038/ncomms1145

Vesicle formation from the nuclear membrane is induced by coexpression of two conserved herpesvirus proteins
journal, April 2007

  • Klupp, B. G.; Granzow, H.; Fuchs, W.
  • Proceedings of the National Academy of Sciences, Vol. 104, Issue 17
  • DOI: 10.1073/pnas.0701757104

Visualizing and quantifying cell phenotype using soft X-ray tomography
journal, January 2012


Computer Visualization of Three-Dimensional Image Data Using IMOD
journal, January 1996

  • Kremer, James R.; Mastronarde, David N.; McIntosh, J. Richard
  • Journal of Structural Biology, Vol. 116, Issue 1
  • DOI: 10.1006/jsbi.1996.0013

The Topological Organization of the Inactive X Chromosome in its Native State
journal, January 2014


Conformational Changes in the Nuclear Lamina Induced by Herpes Simplex Virus Type 1 Require Genes UL31 and UL34
journal, May 2004


Annexation of the interchromosomal space during viral infection
journal, August 2000

  • Monier, Karine; Armas, Juan Carlos González; Etteldorf, Susanne
  • Nature Cell Biology, Vol. 2, Issue 9
  • DOI: 10.1038/35023615

Automatic alignment and reconstruction of images for soft X-ray tomography
journal, February 2012

  • Parkinson, Dilworth Y.; Knoechel, Christian; Yang, Chao
  • Journal of Structural Biology, Vol. 177, Issue 2
  • DOI: 10.1016/j.jsb.2011.11.027

A Herpes Simplex Virus-Derived Replicative Vector Expressing LIF Limits Experimental Demyelinating Disease and Modulates Autoimmunity
journal, May 2013


Herpesvirus Replication Compartments Originate with Single Incoming Viral Genomes
journal, December 2011


Fixation and Permeabilization of Cells and Tissues
journal, May 2008

  • Fischer, A. H.; Jacobson, K. A.; Rose, J.
  • Cold Spring Harbor Protocols, Vol. 2008, Issue 6
  • DOI: 10.1101/pdb.top36