Deletion of the Pseudorabies Virus gE/gI-US9p complex disrupts kinesin KIF1A and KIF5C recruitment during egress, and alters the properties of microtubule-dependent transport in vitro.
Animals
Biological Transport, Active
Cell Line
Gene Deletion
Herpesvirus 1, Suid
/ genetics
Humans
Intracellular Signaling Peptides and Proteins
/ genetics
Kinesins
/ genetics
Lipoproteins
/ genetics
Microtubules
/ genetics
Pseudorabies
/ genetics
Viral Envelope Proteins
/ genetics
Viral Proteins
/ genetics
Virus Release
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
24
02
2020
accepted:
04
05
2020
revised:
18
06
2020
pubmed:
9
6
2020
medline:
11
8
2020
entrez:
9
6
2020
Statut:
epublish
Résumé
During infection of neurons by alphaherpesviruses including Pseudorabies virus (PRV) and Herpes simplex virus type 1 (HSV-1) viral nucleocapsids assemble in the cell nucleus, become enveloped in the cell body then traffic into and down axons to nerve termini for spread to adjacent epithelia. The viral membrane protein US9p and the membrane glycoprotein heterodimer gE/gI play critical roles in anterograde spread of both HSV-1 and PRV, and several models exist to explain their function. Biochemical studies suggest that PRV US9p associates with the kinesin-3 motor KIF1A in a gE/gI-stimulated manner, and the gE/gI-US9p complex has been proposed to recruit KIF1A to PRV for microtubule-mediated anterograde trafficking into or along the axon. However, as loss of gE/gI-US9p essentially abolishes delivery of alphaherpesviruses to the axon it is difficult to determine the microtubule-dependent trafficking properties and motor-composition of Δ(gE/gI-US9p) particles. Alternatively, studies in HSV-1 have suggested that gE/gI and US9p are required for the appearance of virions in the axon because they act upstream, to help assemble enveloped virions in the cell body. We prepared Δ(gE/gI-US9p) mutant, and control parental PRV particles from differentiated cultured neuronal or porcine kidney epithelial cells and quantitated the efficiency of virion assembly, the properties of microtubule-dependent transport and the ability of viral particles to recruit kinesin motors. We find that loss of gE/gI-US9p has no significant effect upon PRV particle assembly but leads to greatly diminished plus end-directed traffic, and enhanced minus end-directed and bidirectional movement along microtubules. PRV particles prepared from infected differentiated mouse CAD neurons were found to be associated with either kinesin KIF1A or kinesin KIF5C, but not both. Loss of gE/gI-US9p resulted in failure to recruit KIF1A and KF5C, but did not affect dynein binding. Unexpectedly, while KIF5C was expressed in undifferentiated and differentiated CAD neurons it was only found associated with PRV particles prepared from differentiated cells.
Identifiants
pubmed: 32511265
doi: 10.1371/journal.ppat.1008597
pii: PPATHOGENS-D-20-00366
pmc: PMC7302734
doi:
Substances chimiques
Intracellular Signaling Peptides and Proteins
0
KIF1A protein, human
0
Lipoproteins
0
US9 protein, Suid herpesvirus 1
0
Viral Envelope Proteins
0
Viral Proteins
0
glycoprotein E, Suid herpesvirus 1
0
KIF5C protein, human
EC 3.6.1.-
Kinesins
EC 3.6.4.4
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Video-Audio Media
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008597Subventions
Organisme : NIAID NIH HHS
ID : R01 AI125244
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK023026
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK041296
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007501
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK098408
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA013330
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Methods Mol Biol. 2010;634:421-30
pubmed: 20677001
J Virol. 2007 Oct;81(20):11363-71
pubmed: 17686845
Neuron. 2010 Nov 18;68(4):610-38
pubmed: 21092854
Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3466-70
pubmed: 11248101
J Virol. 2006 May;80(9):4264-75
pubmed: 16611885
Nat Rev Microbiol. 2011 May;9(5):382-94
pubmed: 21494278
J Neurosci. 2005 Mar 2;25(9):2386-95
pubmed: 15745965
J Virol. 2001 Feb;75(3):1236-51
pubmed: 11152497
J Virol. 2015 Aug;89(15):8088-91
pubmed: 25995254
J Gen Virol. 2012 Jan;93(Pt 1):124-129
pubmed: 21976610
J Virol. 2013 Jan;87(1):403-14
pubmed: 23077321
J Virol. 2008 Aug;82(15):7388-94
pubmed: 18495763
Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11462-7
pubmed: 16055558
Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4873-8
pubmed: 10781094
J Virol. 2001 Jan;75(2):821-33
pubmed: 11134295
J Virol. 2017 May 12;91(11):
pubmed: 28331094
Proc Natl Acad Sci U S A. 2019 Mar 26;116(13):6152-6161
pubmed: 30850543
Physiol Rev. 2008 Jul;88(3):1089-118
pubmed: 18626067
J Virol. 2015 Dec 09;90(4):2102-11
pubmed: 26656703
J Virol. 2015 Nov;89(22):11372-82
pubmed: 26339048
J Virol. 2003 Aug;77(15):8481-94
pubmed: 12857917
J Virol. 2006 Apr;80(7):3167-79
pubmed: 16537585
Mol Biol Cell. 2007 May;18(5):1839-49
pubmed: 17360972
J Neurosci. 1997 Feb 15;17(4):1217-25
pubmed: 9006967
J Virol. 2014 Dec;88(24):14467-78
pubmed: 25297998
J Virol. 2019 Jun 14;93(13):
pubmed: 30996099
PLoS One. 2011 Mar 31;6(3):e17966
pubmed: 21483850
Biophys J. 2010 Jun 2;98(11):2610-8
pubmed: 20513405
Curr Top Membr. 2016;77:185-233
pubmed: 26781833
J Virol. 2018 Sep 26;92(20):
pubmed: 30068641
J Virol. 2007 Jan;81(1):319-31
pubmed: 17035313
Methods Mol Biol. 2007;392:143-58
pubmed: 17951716
Aging Cell. 2003 Dec;2(6):305-18
pubmed: 14677633
IEEE Trans Image Process. 2005 Sep;14(9):1372-83
pubmed: 16190472
J Neurosci Res. 2007 Sep;85(12):2601-9
pubmed: 17335077
Nat Rev Mol Cell Biol. 2009 Oct;10(10):682-96
pubmed: 19773780
J Neurosci. 2006 Jul 5;26(27):7139-42
pubmed: 16822968
J Virol. 2015 Dec 23;90(5):2653-63
pubmed: 26699637
mBio. 2012 May 02;3(2):
pubmed: 22448044
Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5832-7
pubmed: 15795370
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
J Virol. 2005 Sep;79(17):10875-89
pubmed: 16103140
Viruses. 2019 Dec 17;11(12):
pubmed: 31861082
J Virol. 2000 Dec;74(23):10975-83
pubmed: 11069992
PLoS Pathog. 2008 May 16;4(5):e1000065
pubmed: 18483549
J Virol. 2008 Nov;82(21):10613-24
pubmed: 18753205
PLoS Pathog. 2020 Jan 29;16(1):e1007985
pubmed: 31995633
PLoS Biol. 2009 Oct;7(10):e1000216
pubmed: 19823565
J Virol. 2020 Apr 16;94(9):
pubmed: 32075931
J Virol. 2000 Jan;74(2):834-45
pubmed: 10623746
Trends Mol Med. 2002 Apr;8(4):152-5
pubmed: 11927267
Neurochem Int. 2003 Jan;42(1):9-17
pubmed: 12441163
Annu Rev Microbiol. 2012;66:153-76
pubmed: 22726218
J Virol. 2009 Sep;83(17):8315-26
pubmed: 19570876
Cell. 2009 Mar 20;136(6):1148-60
pubmed: 19268344
Virology. 2010 Sep 30;405(2):269-79
pubmed: 20598729
J Virol. 1995 Nov;69(11):7087-98
pubmed: 7474128
J Virol. 1997 Sep;71(9):6455-64
pubmed: 9261363
J Virol. 1997 May;71(5):3603-12
pubmed: 9094633
J Cell Biol. 2006 May 22;173(4):459-61
pubmed: 16717123
J Virol. 2013 Sep;87(17):9431-40
pubmed: 23804637
J Biol Chem. 2019 Apr 19;294(16):6353-6363
pubmed: 30770469
Curr Biol. 2004 Jul 13;14(13):R525-37
pubmed: 15242636
J Neurosci. 2018 Feb 28;38(9):2135-2145
pubmed: 29378864
Adv Virus Res. 1998;51:237-347
pubmed: 9891589
Nat Methods. 2012 Jul;9(7):671-5
pubmed: 22930834
Drug Metab Dispos. 2014 Jan;42(1):62-9
pubmed: 24115750
J Virol. 1999 Aug;73(8):6405-14
pubmed: 10400733
Cell Host Microbe. 2012 Dec 13;12(6):806-14
pubmed: 23245325
J Virol. 2005 Jul;79(14):8835-46
pubmed: 15994777
J Virol. 2020 Jan 31;94(4):
pubmed: 31748394