title: Resolving the assembly state of herpes simplex virus during axon transport by live-cell imaging.
abstract: Neurotropic herpesviruses depend on long-distance axon transport for the initial establishment of latency in peripheral ganglia (retrograde transport) and for viral spread in axons to exposed body surfaces following reactivation (anterograde transport). Images of neurons infected with herpes simplex virus type 1 (HSV-1), acquired using electron microscopy, have led to a debate regarding why different types of viral structures are seen in axons and which of these particles are relevant to the axon transport process. In this study, we applied time-lapse fluorescence microscopy to image HSV-1 virion components actively translocating to distal axons in primary neurons and neuronal cell lines. Key to these findings, only a small fraction of viral particles were engaged in anterograde transport during the egress phase of infection at any given time. By selective analysis of the composition of the subpopulation of actively transporting capsids, a link between transport of fully assembled HSV-1 virions and the neuronal secretory pathway was identified. Last, we have evaluated the seemingly opposing findings made in previous studies of HSV-1 axon transport in fixed cells and demonstrate a limitation to assessing the composition of individual HSV-1 particles using antibody detection methods.
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, 303 E. Chicago Ave., Chicago, IL 60611, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Antinone
authors.forename: Sofia V
authors.initials: SV
authors.lastname: Zaichick
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Smith
mesh_terms: D000818:Animals; D001370:Axonal Transport; D001369:Axons / Q000821:virology*; D015153:Blotting, Western; D002213:Capsid / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D005455:Fluorescent Antibody Technique; D006561:Herpes Simplex / Q000821:virology*; D008854:Microscopy, Electron; D009474:Neurons / Q000821:virology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018139:Simplexvirus / Q000502:physiology*; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000378:metabolism; D014771:Virion / Q000502:physiology*; D014779:Virus Replication
chemical_list: D012333:RNA, Messenger; D014759:Viral Envelope Proteins
references.citation: Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6529-33
references.pmid: 7517552
references.citation: J Virol. 2006 Nov;80(22):11235-40
references.pmid: 16971439
references.citation: J Virol. 1974 Oct;14(4):945-56
references.pmid: 4370986
references.citation: J Virol. 1989 Aug;63(8):3435-43
references.pmid: 2545914
references.citation: J Virol. 2005 Aug;79(15):9566-71
references.pmid: 16014918
references.citation: J Virol. 2003 Jan;77(2):1382-91
references.pmid: 12502854
references.citation: J Gen Virol. 1984 Jan;65 ( Pt 1):55-64
references.pmid: 6319574
references.citation: J Virol. 2005 Apr;79(7):3903-19
references.pmid: 15767393
references.citation: Endocrinology. 2001 Feb;142(2):864-73
references.pmid: 11159860
references.citation: Proc Natl Acad Sci U S A. 1987 Aug;84(15):5454-8
references.pmid: 3037552
references.citation: J Virol. 2007 Jul;81(13):6846-57
references.pmid: 17459934
references.citation: J Neurosci. 1990 Jun;10(6):1974-94
references.pmid: 2162388
references.citation: Brain Res. 2001 Apr 27;899(1-2):260-3
references.pmid: 11311889
references.citation: PLoS One. 2008 Jun 18;3(6):e2382
references.pmid: 18560518
references.citation: J Virol. 2008 Mar;82(6):3109-24
references.pmid: 18160444
references.citation: Arch Virol. 1988;101(1-2):87-104
references.pmid: 2843151
references.citation: J Virol. 2006 Apr;80(7):3592-606
references.pmid: 16537627
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10559-64
references.pmid: 18653756
references.citation: J Virol. 2005 Sep;79(17):11142-50
references.pmid: 16103165
references.citation: J Virol. 2002 Mar;76(6):3065-71
references.pmid: 11861875
references.citation: Future Virol. 2009 Nov 1;4(6):591
references.pmid: 20161665
references.citation: Biotechniques. 2006 Feb;40(2):191-7
references.pmid: 16526409
references.citation: J Virol. 2007 Nov;81(21):11790-7
references.pmid: 17715218
references.citation: J Biol Chem. 1990 Jan 25;265(3):1777-82
references.pmid: 2153143
references.citation: J Neurosci. 1993 Jun;13(6):2515-39
references.pmid: 8388923
references.citation: Traffic. 2008 Sep;9(9):1458-70
references.pmid: 18564370
references.citation: Vet Microbiol. 2002 Apr 22;86(1-2):5-16
references.pmid: 11888685
references.citation: J Neurosci. 1997 Feb 15;17(4):1217-25
references.pmid: 9006967
references.citation: J Virol. 2009 Jan;83(1):250-61
references.pmid: 18945776
references.citation: J Virol. 1997 Apr;71(4):2731-9
references.pmid: 9060626
references.citation: J Gen Virol. 1974 May;23(2):145-57
references.pmid: 4833604
references.citation: Rev Med Virol. 2008 Jan-Feb;18(1):35-51
references.pmid: 17992661
references.citation: J Virol. 1999 Oct;73(10):8503-11
references.pmid: 10482603
references.citation: J Virol. 2002 Oct;76(19):9934-51
references.pmid: 12208970
references.citation: Mol Biol Cell. 2002 Aug;13(8):2795-809
references.pmid: 12181347
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5832-7
references.pmid: 15795370
references.citation: J Virol. 2005 Sep;79(17):10875-89
references.pmid: 16103140
references.citation: Proc Natl Acad Sci U S A. 1987 Aug;84(16):5675-9
references.pmid: 3039500
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10187-92
references.pmid: 17548810
references.citation: J Virol. 1988 Aug;62(8):2596-604
references.pmid: 2839688
references.citation: Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):16034-9
references.pmid: 15505210
references.citation: J Virol. 1998 Jan;72(1):873-5
references.pmid: 9420303
references.citation: J Virol. 2007 Oct;81(20):11363-71
references.pmid: 17686845
references.citation: J Gen Virol. 1991 Mar;72 ( Pt 3):661-8
references.pmid: 1848601
references.citation: J Virol. 2008 Nov;82(21):10613-24
references.pmid: 18753205
references.citation: J Neurosci. 1994 Jan;14(1):318-25
references.pmid: 8283239
references.citation: J Virol. 2006 Nov;80(22):11165-77
references.pmid: 16971450
references.citation: J Neurosci Res. 1997 Aug 15;49(4):485-96
references.pmid: 9285524
references.citation: Infect Immun. 1973 Feb;7(2):272-88
references.pmid: 4348966
references.citation: J Virol. 2000 Feb;74(4):1827-39
references.pmid: 10644356
references.citation: J Virol. 2005 Jun;79(12):7609-16
references.pmid: 15919913
references.citation: J Virol. 2004 Nov;78(21):11519-35
references.pmid: 15479793
references.citation: Nat Neurosci. 2000 May;3(5):445-51
references.pmid: 10769383
references.citation: Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3466-70
references.pmid: 11248101
references.citation: J Virol. 2010 Jun;84(11):5528-39
references.pmid: 20237081
references.citation: J Cell Biol. 1998 Feb 9;140(3):659-74
references.pmid: 9456325
references.citation: J Virol. 2010 Dec;84(24):13031-5
references.pmid: 20943987
references.citation: J Virol Methods. 2002 Aug;105(1):13-23
references.pmid: 12176138
references.citation: J Virol. 1968 May;2(5):507-16
references.pmid: 4301316
references.citation: J Gen Virol. 1972 Jun;15(3):233-5
references.pmid: 4114320
references.citation: Brain Res. 1974 Apr 5;69(2):189-201
references.pmid: 4362812
references.citation: J Virol. 2005 Mar;79(5):3200-5
references.pmid: 15709042
references.citation: Annu Rev Cell Dev Biol. 2002;18:135-61
references.pmid: 12142276
references.citation: Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):7877-82
references.pmid: 12060735
references.citation: J Virol. 2008 Jun;82(11):5198-211
references.pmid: 18353954
references.citation: J Virol. 2009 Apr;83(7):3187-99
references.pmid: 19176621
references.citation: J Virol. 2009 Jul;83(13):6610-23
references.pmid: 19386703
references.citation: J Virol. 2007 Aug;81(15):8337-40
references.pmid: 17522199
references.citation: J Virol. 1999 Aug;73(8):6405-14
references.pmid: 10400733
references.citation: J Virol. 2010 Feb;84(3):1504-12
references.pmid: 19923187