Temporal Viral Genome-Protein Interactions Define Distinct Stages of Productive Herpesviral Infection

MBio
Jill A Dembowski, Neal A DeLuca

Abstract

Herpesviruses utilize multiple mechanisms to redirect host proteins for use in viral processes and to avoid recognition and repression by the host. To investigate dynamic interactions between herpes simplex virus type 1 (HSV-1) DNA and viral and host proteins throughout infection, we developed an approach to identify proteins that associate with the infecting viral genome from nuclear entry through packaging. To accomplish this, virus stocks were prepared in the presence of ethynyl-modified nucleotides to enable covalent tagging of viral genomes after infection for analysis of viral genome-protein interactions by imaging or affinity purification. Affinity purification was combined with stable isotope labeling of amino acids in cell culture (SILAC) mass spectrometry to enable the distinction between proteins that were brought into the cell by the virus or expressed within the infected cell before or during infection. We found that input viral DNA progressed within 6 h through four temporal stages where the genomes sequentially (i) interacted with intrinsic antiviral and DNA damage response proteins, (ii) underwent a robust transcriptional switch mediated largely by ICP4, (iii) engaged in replication, repair, and continued transc...Continue Reading

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Citations

Jun 4, 2019·PLoS Pathogens·Oren Kobiler, Matthew D Weitzman
Nov 21, 2019·Proceedings of the National Academy of Sciences of the United States of America·Thejaswi NagarajuBill Sugden
Nov 26, 2019·FEBS Letters·Matthew CharmanMatthew D Weitzman
Feb 6, 2020·Viruses·Matthew Charman, Matthew D Weitzman
Apr 19, 2020·Human Gene Therapy·Anna C Maurer, Matthew D Weitzman
Nov 6, 2018·Frontiers in Microbiology·Francisco J IbáñezPablo A González
Sep 11, 2019·Journal of Clinical Medicine·Florian Full, Armin Ensser
May 21, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Enosh TomerOren Kobiler
Feb 28, 2019·Proceedings of the National Academy of Sciences of the United States of America·Sarah E Dremel, Neal A DeLuca
Sep 1, 2021·Current Opinion in Virology·Katinka DöhnerBeate Sodeik
Jun 16, 2021·Annual Review of Virology·Alice Fletcher-Etherington, Michael P Weekes

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Methods Mentioned

BETA
PCR
affinity purification

Software Mentioned

Huygens Essential
Scaffold
GraphPad Prism
Mascot
STRING
MaxQuant
Decon
Tableau
Adobe Illustrator
Render

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