HSV-1 single-cell analysis reveals the activation of anti-viral and developmental programs in distinct sub-populations.
Animals
Antiviral Agents
/ metabolism
Cell Cycle
Cell Line
Cell Nucleus
/ metabolism
Gene Expression Regulation, Viral
Herpes Simplex
/ virology
Herpesvirus 1, Human
/ physiology
Humans
Mutation
/ genetics
Signal Transduction
Single-Cell Analysis
Transcription, Genetic
Virus Replication
beta Catenin
/ metabolism
HSV-1
Herpes Simplex
RNA-sequencing
anti-viral
computational biology
development
human
infectious disease
microbiology
single-cell
systems biology
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
15 05 2019
15 05 2019
Historique:
received:
22
02
2019
accepted:
11
05
2019
pubmed:
16
5
2019
medline:
20
2
2020
entrez:
16
5
2019
Statut:
epublish
Résumé
Viral infection is usually studied at the population level by averaging over millions of cells. However, infection at the single-cell level is highly heterogeneous, with most infected cells giving rise to no or few viral progeny while some cells produce thousands. Analysis of Herpes Simplex virus 1 (HSV-1) infection by population-averaged measurements has taught us a lot about the course of viral infection, but has also produced contradictory results, such as the concurrent activation and inhibition of type I interferon signaling during infection. Here, we combine live-cell imaging and single-cell RNA sequencing to characterize viral and host transcriptional heterogeneity during HSV-1 infection of primary human cells. We find extreme variability in the level of viral gene expression among individually infected cells and show that these cells cluster into transcriptionally distinct sub-populations. We find that anti-viral signaling is initiated in a rare group of abortively infected cells, while highly infected cells undergo cellular reprogramming to an embryonic-like transcriptional state. This reprogramming involves the recruitment of β-catenin to the host nucleus and viral replication compartments, and is required for late viral gene expression and progeny production. These findings uncover the transcriptional differences in cells with variable infection outcomes and shed new light on the manipulation of host pathways by HSV-1.
Identifiants
pubmed: 31090537
doi: 10.7554/eLife.46339
pii: 46339
pmc: PMC6570482
doi:
pii:
Substances chimiques
Antiviral Agents
0
beta Catenin
0
Banques de données
GEO
['GSE126042']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK042086
Pays : United States
Organisme : Human Frontier Science Program
ID : post-doctoral fellowship
Pays : International
Informations de copyright
© 2019, Drayman et al.
Déclaration de conflit d'intérêts
ND, PP, LV, ST No competing interests declared
Références
J Virol. 2016 Sep 29;90(20):9406-19
pubmed: 27512060
J Virol. 2013 Dec;87(24):13141-9
pubmed: 24067967
Virology. 2009 Mar 1;385(1):39-46
pubmed: 19070881
Elife. 2018 Feb 16;7:
pubmed: 29451492
mBio. 2018 Mar 13;9(2):
pubmed: 29535194
Proc Natl Acad Sci U S A. 2011 Apr 12;108(15):5954-63
pubmed: 21393571
J Virol. 2016 Jul 27;90(16):7084-7097
pubmed: 27226375
J Virol. 1995 Jan;69(1):49-59
pubmed: 7983745
Mol Cell Proteomics. 2017 Apr;16(4 suppl 1):S92-S107
pubmed: 28179408
Nat Commun. 2015 Nov 20;6:8938
pubmed: 26586423
J Virol. 2018 Mar 28;92(8):
pubmed: 29437966
J Virol. 1980 Oct;36(1):189-203
pubmed: 6255206
Cell. 2015 May 21;161(5):1202-1214
pubmed: 26000488
Crit Rev Oncol Hematol. 2016 Mar;99:141-9
pubmed: 26775730
PLoS One. 2018 Jan 11;13(1):e0191010
pubmed: 29324866
Elife. 2019 May 15;8:
pubmed: 31090537
Science. 2008 Dec 5;322(5907):1511-6
pubmed: 19023046
Sci Signal. 2015 Feb 10;8(363):ra16
pubmed: 25670204
PLoS Pathog. 2013;9(9):e1003611
pubmed: 24086132
PLoS Pathog. 2017 Jan 17;13(1):e1006166
pubmed: 28095497
Gene. 2001 Jun 27;271(2):117-30
pubmed: 11418233
J Virol. 2004 Feb;78(4):1675-84
pubmed: 14747533
PLoS Pathog. 2018 Mar 26;14(3):e1006954
pubmed: 29579120
Cold Spring Harb Perspect Biol. 2012 Sep 01;4(9):a013011
pubmed: 22952399
Nature. 1970 Apr 25;226(5243):325-7
pubmed: 5439728
Cell Syst. 2018 Jun 27;6(6):679-691.e4
pubmed: 29886109
Nucleic Acids Res. 2013 May 1;41(10):e108
pubmed: 23558742
J Virol. 2000 Nov;74(21):10041-54
pubmed: 11024133
PLoS Pathog. 2015 May 27;11(5):e1004939
pubmed: 26018390
Arch Virol. 2017 Oct;162(10):2937-2947
pubmed: 28685286
Front Pharmacol. 2017 May 16;8:270
pubmed: 28559846
J Virol. 2019 Mar 5;93(6):
pubmed: 30626670
J Exp Med. 1938 Apr 30;67(5):725-38
pubmed: 19870751
Cell. 1988 Dec 2;55(5):857-68
pubmed: 2847874
Genome Biol. 2017 Oct 31;18(1):209
pubmed: 29089033
Elife. 2018 Feb 16;7:
pubmed: 29451494
Curr Opin Genet Dev. 2011 Dec;21(6):753-8
pubmed: 22005655
Virology. 2010 Jan 5;396(1):21-9
pubmed: 19879619
J Virol. 2004 Jul;78(13):6744-57
pubmed: 15194749
Nucleus. 2012 Nov-Dec;3(6):526-39
pubmed: 22929056
J Virol. 2013 Dec;87(24):13911-6
pubmed: 24109241
Nature. 1980 May 29;285(5763):329-30
pubmed: 6246451
Int J Mol Med. 2011 Oct;28(4):595-8
pubmed: 21725588
J Virol. 2006 Aug;80(15):7600-12
pubmed: 16840339
J Virol. 1985 Nov;56(2):558-70
pubmed: 2997476
PLoS Biol. 2012 Jan;10(1):e1001249
pubmed: 22291574
Cell Rep. 2014 Aug 21;8(4):1026-36
pubmed: 25127138
Sci Rep. 2016 Jun 29;6:28075
pubmed: 27354008
Nat Microbiol. 2019 Jan;4(1):164-176
pubmed: 30420784
J Virol. 2014 Jun;88(11):6205-12
pubmed: 24648454
Nat Rev Clin Oncol. 2015 Aug;12(8):445-64
pubmed: 25850553
Mol Syst Biol. 2012 Apr 24;8:579
pubmed: 22531119
Virol J. 2016 Mar 08;13:38
pubmed: 26952111
J Virol. 2015 Dec 16;90(5):2503-13
pubmed: 26676778
Viruses. 2017 Aug 07;9(8):
pubmed: 28783105
Development. 2011 Oct;138(20):4341-50
pubmed: 21903672
Oncoimmunology. 2015 Dec 8;5(1):e1115641
pubmed: 26942095
Adv Exp Med Biol. 2018;1045:63-84
pubmed: 29896663
J Virol. 2017 Nov 14;91(23):
pubmed: 28904192
Cells. 2014 May 20;3(2):438-54
pubmed: 24852129
Nat Rev Microbiol. 2013 May;11(5):327-36
pubmed: 23524517
PLoS Pathog. 2016 Dec 6;12(12):e1006082
pubmed: 27923068
J Gen Virol. 1986 Dec;67 ( Pt 12):2571-85
pubmed: 3025339
Science. 2002 Aug 16;297(5584):1183-6
pubmed: 12183631
Nat Immunol. 2018 Jan;19(1):53-62
pubmed: 29180807
Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):17031-6
pubmed: 12481033
Cell Signal. 2014 Mar;26(3):570-9
pubmed: 24308963
J Immunother Cancer. 2015 Sep 15;3:43
pubmed: 26380088
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Cell Host Microbe. 2015 Oct 14;18(4):424-32
pubmed: 26468746
J Virol. 2019 Jun 28;93(14):
pubmed: 31068418
Proc Natl Acad Sci U S A. 1975 Apr;72(4):1276-80
pubmed: 165503
Cell. 2015 Jan 29;160(3):381-92
pubmed: 25635454
Rev Med Virol. 2016 Sep;26(5):340-55
pubmed: 27273590
Nature. 2005 Apr 14;434(7035):843-50
pubmed: 15829953
EMBO J. 2016 Jul 1;35(13):1385-99
pubmed: 27234299
Science. 2016 Apr 8;352(6282):189-96
pubmed: 27124452
J Virol. 2014 Jun;88(12):6847-61
pubmed: 24719411
Nature. 2010 Jul 8;466(7303):267-71
pubmed: 20581820
J Virol. 1974 Jul;14(1):8-19
pubmed: 4365321
Virus Res. 2018 Sep 2;256:29-37
pubmed: 30077727
Proteomics. 2015 Jun;15(12):1957-67
pubmed: 25809282
J Virol. 1987 Feb;61(2):276-84
pubmed: 3027360
Nat Commun. 2016 Nov 10;7:13348
pubmed: 27830700
J Gen Microbiol. 1959 Feb;20(1):105-12
pubmed: 13631187
mBio. 2017 Nov 7;8(6):
pubmed: 29114028
J Virol. 2018 Sep 12;92(19):
pubmed: 29997210
J Virol. 2003 Mar;77(6):3680-9
pubmed: 12610143
mBio. 2018 Jul 17;9(4):
pubmed: 30018111
J Virol. 1996 Mar;70(3):1759-67
pubmed: 8627698
Nature. 2015 Jul 9;523(7559):231-5
pubmed: 25970248
Virology. 2012 Mar 1;424(1):11-7
pubmed: 22222212
Nature. 2009 Sep 24;461(7263):520-3
pubmed: 19710653
Nat Commun. 2015 May 20;6:7126
pubmed: 25989971
Proc Natl Acad Sci U S A. 2005 May 24;102(21):7571-6
pubmed: 15897453
Cell Syst. 2018 Dec 26;7(6):627-642.e6
pubmed: 30471916
Cell Rep. 2017 Nov 7;21(6):1692-1704
pubmed: 29117571
Nat Commun. 2018 Nov 28;9(1):5037
pubmed: 30487586
Virology. 2008 May 10;374(2):487-94
pubmed: 18279905
Mol Cell Proteomics. 2017 Dec;16(12):2079-2097
pubmed: 28972080
Dermatol Clin. 2019 Jan;37(1):73-82
pubmed: 30466690
J Bacteriol. 1945 Aug;50(2):131-5
pubmed: 16560982