Cellular Mechanisms of Alpha Herpesvirus Egress: Live Cell Fluorescence Microscopy of Pseudorabies Virus Exocytosis
Pseudorabies virus, an alpha herpesvirus, is an important veterinary pathogen, and related to human varicella-zoster virus and herpes simplex viruses. New alpha herpesvirus particles are assembled inside an infected cell, and must exit from the infected cell by taking advantage of cellular mechanisms. How these virus particles are transported inside the infected cell and secreted at the cell surface is not understood in great detail. In particular, how this process unfolds over time is not easily observed using previous methods. In this study, we developed a new method to observe this egress process. Using this method, we described how virus particles move on their way out: individual virus particles travel to the cell surface, directly to the exit site, where they pause for several seconds before crossing out of the cell. We identified several cellular proteins that are involved in this process. After exiting, virus particles remained stuck to the outer cell surface. Finally, we draw connections between our observations and other recent studies to propose an integrated model of how alpha herpesvirus particles exit from infected cells.
Vyšlo v časopise:
Cellular Mechanisms of Alpha Herpesvirus Egress: Live Cell Fluorescence Microscopy of Pseudorabies Virus Exocytosis. PLoS Pathog 10(12): e32767. doi:10.1371/journal.ppat.1004535
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004535
Souhrn
Pseudorabies virus, an alpha herpesvirus, is an important veterinary pathogen, and related to human varicella-zoster virus and herpes simplex viruses. New alpha herpesvirus particles are assembled inside an infected cell, and must exit from the infected cell by taking advantage of cellular mechanisms. How these virus particles are transported inside the infected cell and secreted at the cell surface is not understood in great detail. In particular, how this process unfolds over time is not easily observed using previous methods. In this study, we developed a new method to observe this egress process. Using this method, we described how virus particles move on their way out: individual virus particles travel to the cell surface, directly to the exit site, where they pause for several seconds before crossing out of the cell. We identified several cellular proteins that are involved in this process. After exiting, virus particles remained stuck to the outer cell surface. Finally, we draw connections between our observations and other recent studies to propose an integrated model of how alpha herpesvirus particles exit from infected cells.
Zdroje
1. MettenleiterTC, MüllerF, GranzowH, KluppBG (2013) The way out: what we know and do not know about herpesvirus nuclear egress. Cell Microbiol 15: 170–178 doi:10.1111/cmi.12044
2. TurcotteS, LetellierJ, LippéR (2005) Herpes simplex virus type 1 capsids transit by the trans-Golgi network, where viral glycoproteins accumulate independently of capsid egress. J Virol 79: 8847–8860 doi:10.1128/JVI.79.14.8847-8860.2005
3. Rémillard-LabrosseG, LippéR (2009) Meeting of conventional and unconventional pathways at the TGN. Commun Integr Biol 2: 434–436.
4. SugimotoK, UemaM, SagaraH, TanakaM, SataT, et al. (2008) Simultaneous tracking of capsid, tegument, and envelope protein localization in living cells infected with triply fluorescent herpes simplex virus 1. J Virol 82: 5198–5211 doi:10.1128/JVI.02681-07
5. HollinsheadM, JohnsHL, SayersCL, Gonzalez-LopezC, SmithGL, et al. (2012) Endocytic tubules regulated by Rab GTPases 5 and 11 are used for envelopment of herpes simplex virus. EMBO J 31: 4204–4220 doi:10.1038/emboj.2012.262
6. JohnsHL, Gonzalez-LopezC, SayersCL, HollinsheadM, ElliottG (2014) Rab6 dependent post-Golgi trafficking of HSV1 envelope proteins to sites of virus envelopment. Traffic 15: 157–178 doi:10.1111/tra.12134
7. HutagalungAH, NovickPJ (2011) Role of Rab GTPases in membrane traffic and cell physiology. Physiol Rev 91: 119–149 doi:10.1152/physrev.00059.2009
8. StegenC, YakovaY, HenaffD, NadjarJ, DuronJ, et al. (2013) Analysis of virion-incorporated host proteins required for herpes simplex virus type 1 infection through a RNA interference screen. PLoS ONE 8: e53276 doi:10.1371/journal.pone.0053276
9. ZennerHL, YoshimuraS-I, BarrFA, CrumpCM (2011) Analysis of Rab GTPase-activating proteins indicates that Rab1a/b and Rab43 are important for herpes simplex virus 1 secondary envelopment. J Virol 85: 8012–8021 doi:10.1128/JVI.00500-11
10. MingoRM, HanJ, NewcombWW, BrownJC (2012) Replication of herpes simplex virus: egress of progeny virus at specialized cell membrane sites. J Virol 86: 7084–7097 doi:10.1128/JVI.00463-12
11. SankaranarayananS, De AngelisD, RothmanJE, RyanTA (2000) The Use of pHluorins for Optical Measurements of Presynaptic Activity. Biophys J 79: 2199–2208 doi:10.1016/S0006-3495(00)76468-X
12. del RioT, Ch'ngTH, FloodEA, GrossSP, EnquistLW (2005) Heterogeneity of a fluorescent tegument component in single pseudorabies virus virions and enveloped axonal assemblies. J Virol 79: 3903–3919 doi:10.1128/JVI.79.7.3903-3919.2005
13. CrumpCM, BruunB, BellS, PomeranzLE, MinsonT, et al. (2004) Alphaherpesvirus glycoprotein M causes the relocalization of plasma membrane proteins. J Gen Virol 85: 3517–3527 doi:10.1099/vir.0.80361-0
14. SzilágyiJF, CunninghamC (1991) Identification and characterization of a novel non-infectious herpes simplex virus-related particle. J Gen Virol 72 (Pt 3) 661–668.
15. RixonFJ, AddisonC, McLauchlanJ (1992) Assembly of enveloped tegument structures (L particles) can occur independently of virion maturation in herpes simplex virus type 1-infected cells. J Gen Virol 73 (Pt 2) 277–284.
16. ParoutisP, TouretN, GrinsteinS (2004) The pH of the secretory pathway: measurement, determinants, and regulation. Physiology (Bethesda) 19: 207–215 doi:10.1152/physiol.00005.2004
17. TumaPL, HubbardAL (2003) Transcytosis: crossing cellular barriers. Physiol Rev 83: 871–932 doi:10.1152/physrev.00001.2003
18. McNabAR, DesaiP, PersonS, RoofLL, ThomsenDR, et al. (1998) The product of the herpes simplex virus type 1 UL25 gene is required for encapsidation but not for cleavage of replicated viral DNA. J Virol 72: 1060–1070.
19. KluppBG, GranzowH, KeilGM, MettenleiterTC (2006) The capsid-associated UL25 protein of the alphaherpesvirus pseudorabies virus is nonessential for cleavage and encapsidation of genomic DNA but is required for nuclear egress of capsids. J Virol 80: 6235–6246 doi:10.1128/JVI.02662-05
20. RadtkeK, DöhnerK, SodeikB (2006) Viral interactions with the cytoskeleton: a hitchhiker's guide to the cell. Cell Microbiol 8: 387–400 doi:10.1111/j.1462-5822.2005.00679.x
21. SmithG (2012) Herpesvirus Transport to the Nervous System and Back Again. Annu Rev Microbiol 66: 153–176 doi:10.1146/annurev-micro-092611-150051
22. KramerT, EnquistLW (2013) Directional spread of alphaherpesviruses in the nervous system. Viruses 5: 678–707 doi:10.3390/v5020678
23. GrigorievI, YuKL, Martinez-SanchezE, Serra-MarquesA, SmalI, et al. (2011) Rab6, Rab8, and MICAL3 Cooperate in Controlling Docking and Fusion of Exocytotic Carriers. Current Biology 21: 967–974 doi:10.1016/j.cub.2011.04.030
24. GrigorievI, SplinterD, KeijzerN, WulfPS, DemmersJ, et al. (2007) Rab6 Regulates Transport and Targeting of Exocytotic Carriers. Developmental Cell 13: 305–314 doi:10.1016/j.devcel.2007.06.010
25. ToomreD, SteyerJA, KellerP, AlmersW, SimonsK (2000) Fusion of constitutive membrane traffic with the cell surface observed by evanescent wave microscopy. The Journal of Cell Biology 149: 33–40 doi:10.1083/jcb.149.1.33
26. GranzowH, KluppBG, FuchsW, VeitsJ, OsterriederN, et al. (2001) Egress of alphaherpesviruses: comparative ultrastructural study. J Virol 75: 3675–3684 doi:10.1128/JVI.75.8.3675-3684.2001
27. ZennerHL, MauricioR, BantingG, CrumpCM (2013) Herpes simplex virus 1 counteracts tetherin restriction via its virion host shutoff activity. J Virol 87: 13115–13123 doi:10.1128/JVI.02167-13
28. ShuklaD, SpearPG (2001) Herpesviruses and heparan sulfate: an intimate relationship in aid of viral entry. J Clin Invest 108: 503–510 doi:10.1172/JCI13799
29. RobertsKL, BainesJD (2010) Myosin Va enhances secretion of herpes simplex virus 1 virions and cell surface expression of viral glycoproteins. J Virol 84: 9889–9896 doi:10.1128/JVI.00732-10
30. TaylorMP, KoyuncuOO, EnquistLW (2011) Subversion of the actin cytoskeleton during viral infection. Nat Rev Microbiol 9: 427–439 doi:10.1038/nrmicro2574
31. FavoreelHW, EnquistLW, FeierbachB (2007) Actin and Rho GTPases in herpesvirus biology. Trends Microbiol 15: 426–433 doi:10.1016/j.tim.2007.08.003
32. Ohara-ImaizumiM, OhtsukaT, MatsushimaS, AkimotoY, NishiwakiC, et al. (2005) ELKS, a protein structurally related to the active zone-associated protein CAST, is expressed in pancreatic beta cells and functions in insulin exocytosis: interaction of ELKS with exocytotic machinery analyzed by total internal reflection fluorescence microscopy. Mol Biol Cell 16: 3289–3300 doi:10.1091/mbc.E04-09-0816
33. Miserey-LenkeiS, ChalanconG, BardinS, FormstecherE, GoudB, et al. (2010) Rab and actomyosin-dependent fission of transport vesicles at the Golgi complex. Nat Cell Biol 12: 645–654 doi:10.1038/ncb2067
34. HsuVW, PrekerisR (2010) Transport at the recycling endosome. Curr Opin Cell Biol 22: 528–534 doi:10.1016/j.ceb.2010.05.008
35. SahlenderDA, RobertsRC, ArdenSD, SpudichG, TaylorMJ, et al. (2005) Optineurin links myosin VI to the Golgi complex and is involved in Golgi organization and exocytosis. The Journal of Cell Biology 169: 285–295 doi:10.1083/jcb.200501162
36. HuberLA, PimplikarS, PartonRG, VirtaH, ZerialM, et al. (1993) Rab8, a small GTPase involved in vesicular traffic between the TGN and the basolateral plasma membrane. The Journal of Cell Biology 123: 35–45.
37. KramerT, GrecoTM, TaylorMP, AmbrosiniAE, CristeaIM, et al. (2012) Kinesin-3 mediates axonal sorting and directional transport of alphaherpesvirus particles in neurons. Cell Host Microbe 12: 806–814 doi:10.1016/j.chom.2012.10.013
38. NaghaviMH, GundersenGG, WalshD (2013) Plus-end tracking proteins, CLASPs, and a viral Akt mimic regulate herpesvirus-induced stable microtubule formation and virus spread. Proc Natl Acad Sci USA 110: 18268–18273 doi:10.1073/pnas.1310760110
39. LansbergenG, GrigorievI, Mimori-KiyosueY, OhtsukaT, HigaS, et al. (2006) CLASPs attach microtubule plus ends to the cell cortex through a complex with LL5beta. Developmental Cell 11: 21–32 doi:10.1016/j.devcel.2006.05.012
40. ZerboniL, SenN, OliverSL, ArvinAM (2014) Molecular mechanisms of varicella zoster virus pathogenesis. Nat Rev Microbiol 12: 197–210 doi:10.1038/nrmicro3215
41. JollyC, SattentauQJ (2007) Regulated secretion from CD4+ T cells. Trends Immunol 28: 474–481 doi:10.1016/j.it.2007.08.008
42. KoyuncuOO, HogueIB, EnquistLW (2013) Virus infections in the nervous system. Cell Host Microbe 13: 379–393 doi:10.1016/j.chom.2013.03.010
43. HidaY, OhtsukaT (2010) CAST and ELKS proteins: structural and functional determinants of the presynaptic active zone. J Biochem 148: 131–137 doi:10.1093/jb/mvq065
44. FukudaM (2008) Regulation of secretory vesicle traffic by Rab small GTPases. Cell Mol Life Sci 65: 2801–2813 doi:10.1007/s00018-008-8351-4
45. Miranda-SaksenaM, BoadleRA, AggarwalA, TijonoB, RixonFJ, et al. (2009) Herpes simplex virus utilizes the large secretory vesicle pathway for anterograde transport of tegument and envelope proteins and for viral exocytosis from growth cones of human fetal axons. J Virol 83: 3187–3199 doi:10.1128/JVI.01579-08
46. Bello-MoralesR, CrespilloAJ, Fraile-RamosA, TabarésE, AlcinaA, et al. (2012) Role of the small GTPase Rab27a during herpes simplex virus infection of oligodendrocytic cells. BMC Microbiol 12: 265 doi:10.1186/1471-2180-12-265
47. GoedhartJ, Stetten vonD, Noirclerc-SavoyeM, LelimousinM, JoosenL, et al. (2012) Structure-guided evolution of cyan fluorescent proteins towards a quantum yield of 93%. Nat Comms 3: 751 doi:10.1038/ncomms1738
48. SmithGA, EnquistLW (2000) A self-recombining bacterial artificial chromosome and its application for analysis of herpesvirus pathogenesis.
49. CollerKE, LeeJI-H, UedaA, SmithGA (2007) The capsid and tegument of the alphaherpesviruses are linked by an interaction between the UL25 and VP1/2 proteins. J Virol 81: 11790–11797 doi:10.1128/JVI.01113-07
50. MatovA, ApplegateK, KumarP, ThomaC, KrekW (2010) Analysis of microtubule dynamic instability using a plus-end growth marker. Nat methods 7: 761–768.
51. TsuboiT, FukudaM (2006) Rab3A and Rab27A cooperatively regulate the docking step of dense-core vesicle exocytosis in PC12 cells. Journal of Cell Science 119: 2196–2203 doi:10.1242/jcs.02962
52. ChoudhuryA, DominguezM, PuriV, SharmaDK, NaritaK, et al. (2002) Rab proteins mediate Golgi transport of caveola-internalized glycosphingolipids and correct lipid trafficking in Niemann-Pick C cells. J Clin Invest 109: 1541–1550 doi:10.1172/JCI15420
53. NachuryMV, LoktevAV, ZhangQ, WestlakeCJ, PeränenJ, et al. (2007) A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis. Cell 129: 1201–1213 doi:10.1016/j.cell.2007.03.053
54. KratchmarovR, TaylorMP, EnquistLW (2013) Role of Us9 phosphorylation in axonal sorting and anterograde transport of pseudorabies virus. PLoS ONE 8: e58776 doi:10.1371/journal.pone.0058776
55. TaylorMP, KratchmarovR, EnquistLW (2013) Live cell imaging of alphaherpes virus anterograde transport and spread. J Vis Exp doi:10.3791/50723
56. SchindelinJ, Arganda-CarrerasI, FriseE, KaynigV, LongairM, et al. (2012) Fiji: an open-source platform for biological-image analysis. Nat Meth 9: 676–682 doi:10.1038/nmeth.2019
57. MeijeringE, DzyubachykO, SmalI (2012) Methods for cell and particle tracking. Meth Enzymol 504: 183–200 doi:10.1016/B978-0-12-391857-4.00009-4
58. TarantinoN, TinevezJ-Y, CrowellEF, BoissonB, HenriquesR, et al. (2014) TNF and IL-1 exhibit distinct ubiquitin requirements for inducing NEMO-IKK supramolecular structures. The Journal of Cell Biology 204: 231–245 doi:10.1083/jcb.201307172
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