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Abstract

Nuclear egress of herpesvirus capsids across the intact nuclear envelope is an exceptional vesicle-mediated nucleocytoplasmic translocation resulting in the delivery of herpesvirus capsids into the cytosol. Budding of the (nucleo)capsid at and scission from the inner nuclear membrane (INM) is mediated by the viral nuclear egress complex (NEC) resulting in a transiently enveloped virus particle in the perinuclear space followed by fusion of the primary envelope with the outer nuclear membrane (ONM). The dimeric NEC oligomerizes into a honeycomb-shaped coat underlining the INM to induce membrane curvature and scission. Mutational analyses complemented structural data defining functionally important regions. Questions remain, including where and when the NEC is formed and how membrane curvature is mediated, vesicle formation is regulated, and directionality is secured. The composition of the primary enveloped virion and the machinery mediating fusion of the primary envelope with the ONM is still debated. While NEC-mediated budding apparently follows a highly conserved mechanism, species and/or cell type–specific differences complicate understanding of later steps.

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2023-09-29
2024-04-29
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Literature Cited

  1. 1.
    Stackpole CW. 1969. Herpes-type virus of the frog renal adenocarcinoma. I. Virus development in tumor transplants maintained at low temperature. J. Virol. 4:75–93
    [Google Scholar]
  2. 2.
    Campadelli-Fiume G, Roizman B. 2006. The egress of herpesviruses from cells: the unanswered questions. J. Virol. 80:6716–17
    [Google Scholar]
  3. 3.
    Campadelli-Fiume G, Roizman B. 2006. The egress of herpesviruses from cells: the unanswered questions—author's reply. J. Virol. 80:6717–19
    [Google Scholar]
  4. 4.
    Mettenleiter TC, Minson T. 2006. Egress of alphaherpesviruses. J. Virol. 80:1610–11
    [Google Scholar]
  5. 5.
    Mettenleiter TC, Minson T. 2006. Egress of alphaherpesviruses—author's reply. J. Virol. 80:1611–12
    [Google Scholar]
  6. 6.
    Roizman B, Sears AE 1990. Herpes simplex viruses and their replication. Fields’ Virology BN Fields, DM Knipe, RM Chanock, MS Hirsch, JL Melnick et al.1795–894. New York: Raven. , 2nd ed..
    [Google Scholar]
  7. 7.
    Newcomb WW, Fontana J, Winkler DC, Cheng N, Heymann JB, Steven AC. 2017. The primary enveloped virion of herpes simplex virus 1: its role in nuclear egress. mBio 8:3e00825–17
    [Google Scholar]
  8. 8.
    Reynolds AE, Wills EG, Roller RJ, Ryckman BJ, Baines JD. 2002. Ultrastructural localization of the herpes simplex virus type 1 UL31, UL34, and US3 proteins suggests specific roles in primary envelopment and egress of nucleocapsids. J. Virol. 76:8939–52
    [Google Scholar]
  9. 9.
    Klupp BG, Granzow H, Mettenleiter TC. 2000. Primary envelopment of pseudorabies virus at the nuclear membrane requires the UL34 gene product. J. Virol. 74:10063–73
    [Google Scholar]
  10. 10.
    Browne H, Bell S, Minson T, Wilson DW. 1996. An endoplasmic reticulum-retained herpes simplex virus glycoprotein H is absent from secreted virions: evidence for reenvelopment during egress. J. Virol. 70:4311–16
    [Google Scholar]
  11. 11.
    Skepper JN, Whiteley A, Browne H, Minson A. 2001. Herpes simplex virus nucleocapsids mature to progeny virions by an envelopment → deenvelopment → reenvelopment pathway. J. Virol. 75:5697–702
    [Google Scholar]
  12. 12.
    Maric M, Haugo AC, Dauer W, Johnson D, Roller RJ 2014. Nuclear envelope breakdown induced by herpes simplex virus type 1 involves the activity of viral fusion proteins. Virology 460–461:128–37
    [Google Scholar]
  13. 13.
    Klupp BG, Granzow H, Mettenleiter TC. 2011. Nuclear envelope breakdown can substitute for primary envelopment-mediated nuclear egress of herpesviruses. J. Virol. 85:8285–92
    [Google Scholar]
  14. 14.
    Wild P, Senn C, Manera CL, Sutter E, Schraner EM et al. 2009. Exploring the nuclear envelope of herpes simplex virus 1-infected cells by high-resolution microscopy. J. Virol. 83:408–19
    [Google Scholar]
  15. 15.
    Liang L, Tanaka M, Kawaguchi Y, Baines JD. 2004. Cell lines that support replication of a novel herpes simplex virus 1 UL31 deletion mutant can properly target UL34 protein to the nuclear rim in the absence of UL31. Virology 329:68–76
    [Google Scholar]
  16. 16.
    Fuchs W, Klupp BG, Granzow H, Osterrieder N, Mettenleiter TC. 2002. The interacting UL31 and UL34 gene products of pseudorabies virus are involved in egress from the host-cell nucleus and represent components of primary enveloped but not mature virions. J. Virol. 76:364–78
    [Google Scholar]
  17. 17.
    Mettenleiter TC, Klupp BG, Granzow H. 2009. Herpesvirus assembly: an update. Virus Res. 143:222–34
    [Google Scholar]
  18. 18.
    Hage S, Marschall M. 2022.. ‘ Come together’—The regulatory interaction of herpesviral nuclear egress proteins comprises both essential and accessory functions. Cells 11:1837
    [Google Scholar]
  19. 19.
    Roller RJ, Baines JD. 2017. Herpesvirus nuclear egress. Adv. Anat. Embryol. Cell Biol. 223:143–69
    [Google Scholar]
  20. 20.
    Lee CP, Chen MR. 2021. Conquering the nuclear envelope barriers by EBV lytic replication. Viruses 13:4702
    [Google Scholar]
  21. 21.
    Mettenleiter TC. 2016. Breaching the barrier—the nuclear envelope in virus infection. J. Mol. Biol. 428:1949–61
    [Google Scholar]
  22. 22.
    Mettenleiter TC, Muller F, Granzow H, Klupp BG. 2013. The way out: what we know and do not know about herpesvirus nuclear egress. Cell. Microbiol. 15:170–78
    [Google Scholar]
  23. 23.
    Hellberg T, Passvogel L, Schulz KS, Klupp BG, Mettenleiter TC. 2016. Nuclear egress of herpesviruses: the prototypic vesicular nucleocytoplasmic transport. Adv. Virus Res. 94:81–140
    [Google Scholar]
  24. 24.
    Lv Y, Zhou S, Gao S, Deng H. 2019. Remodeling of host membranes during herpesvirus assembly and egress. Protein Cell 10:315–26
    [Google Scholar]
  25. 25.
    Sanchez V, Britt W. 2021. Human cytomegalovirus egress: overcoming barriers and co-opting cellular functions. Viruses 14:115
    [Google Scholar]
  26. 26.
    Roller RJ, Johnson DC. 2021. Herpesvirus nuclear egress across the outer nuclear membrane. Viruses 13:122356
    [Google Scholar]
  27. 27.
    Draganova EB, Thorsen MK, Heldwein EE. 2021. Nuclear egress. Curr. Issues Mol. Biol. 41:125–70
    [Google Scholar]
  28. 28.
    Bigalke JM, Heldwein EE. 2016. Nuclear exodus: Herpesviruses lead the way. Annu. Rev. Virol. 3:387–409
    [Google Scholar]
  29. 29.
    Arii J. 2021. Host and viral factors involved in nuclear egress of herpes simplex virus 1. Viruses 13:5754
    [Google Scholar]
  30. 30.
    Farkas A, Bohnsack KE. 2021. Capture and delivery of tail-anchored proteins to the endoplasmic reticulum. J. Cell Biol. 220:8e202105004
    [Google Scholar]
  31. 31.
    Katta SS, Smoyer CJ, Jaspersen SL. 2014. Destination: inner nuclear membrane. Trends Cell Biol. 24:221–29
    [Google Scholar]
  32. 32.
    Schmeiser C, Borst E, Sticht H, Marschall M, Milbradt J. 2013. The cytomegalovirus egress proteins pUL50 and pUL53 are translocated to the nuclear envelope through two distinct modes of nuclear import. J. Gen. Virol. 94:2056–69
    [Google Scholar]
  33. 33.
    Funk C, Marques da Silveira ESD, Ott M, Raschbichler V, Bailer SM 2021. The HSV1 tail-anchored membrane protein pUL34 contains a basic motif that supports active transport to the inner nuclear membrane prior to formation of the nuclear egress complex. Viruses 13:81544
    [Google Scholar]
  34. 34.
    Blenski M, Kehlenbach RH. 2019. Targeting of LRRC59 to the endoplasmic reticulum and the inner nuclear membrane. Int. J. Mol. Sci. 20:2334
    [Google Scholar]
  35. 35.
    Haugo AC, Szpara ML, Parsons L, Enquist LW, Roller RJ. 2011. Herpes simplex virus 1 pUL34 plays a critical role in cell-to-cell spread of virus in addition to its role in virus replication. J. Virol. 85:7203–15
    [Google Scholar]
  36. 36.
    Arii J, Takeshima K, Maruzuru Y, Koyanagi N, Nakayama Y et al. 2022. Role of the arginine cluster in the disordered domain of herpes simplex virus 1 UL34 for the recruitment of ESCRT-III for viral primary envelopment. J. Virol. 96:e0170421
    [Google Scholar]
  37. 37.
    Thorsen MK, Lai A, Lee MW, Hoogerheide DP, Wong GCL et al. 2021. Highly basic clusters in the herpes simplex virus 1 nuclear egress complex drive membrane budding by inducing lipid ordering. mBio 12:e0154821
    [Google Scholar]
  38. 38.
    Bjerke SL, Cowan JM, Kerr JK, Reynolds AE, Baines JD, Roller RJ. 2003. Effects of charged cluster mutations on the function of herpes simplex virus type 1 U(L)34 protein. J. Virol. 77:7601–10
    [Google Scholar]
  39. 39.
    Meyer GA, Radsak KD. 2000. Identification of a novel signal sequence that targets transmembrane proteins to the nuclear envelope inner membrane. J. Biol. Chem. 275:3857–66
    [Google Scholar]
  40. 40.
    Passvogel L, Trube P, Schuster F, Klupp BG, Mettenleiter TC. 2013. Mapping of sequences in Pseudorabies virus pUL34 that are required for formation and function of the nuclear egress complex. J. Virol. 87:4475–85
    [Google Scholar]
  41. 41.
    Ye GJ, Roizman B. 2000. The essential protein encoded by the UL31 gene of herpes simplex virus 1 depends for its stability on the presence of UL34 protein. PNAS 97:11002–7
    [Google Scholar]
  42. 42.
    Ott M, Tascher G, Hassdenteufel S, Zimmermann R, Haas J, Bailer SM. 2011. Functional characterization of the essential tail anchor of the herpes simplex virus type 1 nuclear egress protein pUL34. J. Gen. Virol. 92:2734–45
    [Google Scholar]
  43. 43.
    Gonnella R, Farina A, Santarelli R, Raffa S, Feederle R et al. 2005. Characterization and intracellular localization of the Epstein-Barr virus protein BFLF2: interactions with BFRF1 and with the nuclear lamina. J. Virol. 79:3713–27
    [Google Scholar]
  44. 44.
    Luitweiler EM, Henson BW, Pryce EN, Patel V, Coombs G et al. 2013. Interactions of the Kaposi's sarcoma-associated herpesvirus nuclear egress complex: ORF69 is a potent factor for remodeling cellular membranes. J. Virol. 87:3915–29
    [Google Scholar]
  45. 45.
    Stiekema M, Houben F, Verheyen F, Borgers M, Menzel J et al. 2022. The role of lamins in the nucleoplasmic reticulum, a pleiomorphic organelle that enhances nucleo-cytoplasmic interplay. Front. Cell Dev. Biol. 10:914286
    [Google Scholar]
  46. 46.
    Simpson-Holley M, Colgrove RC, Nalepa G, Harper JW, Knipe DM. 2005. Identification and functional evaluation of cellular and viral factors involved in the alteration of nuclear architecture during herpes simplex virus 1 infection. J. Virol. 79:12840–51
    [Google Scholar]
  47. 47.
    Funk C, Ott M, Raschbichler V, Nagel CH, Binz A et al. 2015. The herpes simplex virus protein pUL31 escorts nucleocapsids to sites of nuclear egress, a process coordinated by its N-terminal domain. PLOS Pathog. 11:e1004957
    [Google Scholar]
  48. 48.
    Passvogel L, Klupp BG, Granzow H, Fuchs W, Mettenleiter TC. 2015. Functional characterization of nuclear trafficking signals in pseudorabies virus pUL31. J. Virol. 89:2002–12
    [Google Scholar]
  49. 49.
    Lotzerich M, Ruzsics Z, Koszinowski UH. 2006. Functional domains of murine cytomegalovirus nuclear egress protein M53/p38. J. Virol. 80:73–84
    [Google Scholar]
  50. 50.
    Klupp BG, Hellberg T, Ronfeldt S, Franzke K, Fuchs W, Mettenleiter TC. 2018. Function of the nonconserved N-terminal domain of pseudorabies virus pUL31 in nuclear egress. J. Virol. 92:15e00566–18
    [Google Scholar]
  51. 51.
    Bailer SM. 2017. Venture from the interior—Herpesvirus pUL31 escorts capsids from nucleoplasmic replication compartments to sites of primary envelopment at the inner nuclear membrane. Cells 6:446
    [Google Scholar]
  52. 52.
    Wang J, Yuan S, Zhu D, Tang H, Wang N et al. 2018. Structure of the herpes simplex virus type 2 C-capsid with capsid-vertex-specific component. Nat. Commun. 9:3668
    [Google Scholar]
  53. 53.
    Yang K, Wills E, Lim HY, Zhou ZH, Baines JD. 2014. Association of herpes simplex virus pUL31 with capsid vertices and components of the capsid vertex-specific complex. J. Virol. 88:3815–25
    [Google Scholar]
  54. 54.
    Leelawong M, Guo D, Smith GA. 2011. A physical link between the pseudorabies virus capsid and the nuclear egress complex. J. Virol. 85:11675–84
    [Google Scholar]
  55. 55.
    Lye MF, Sharma M, El Omari K, Filman DJ, Schuermann JP et al. 2015. Unexpected features and mechanism of heterodimer formation of a herpesvirus nuclear egress complex. EMBO J. 34:2937–52
    [Google Scholar]
  56. 56.
    Walzer SA, Egerer-Sieber C, Sticht H, Sevvana M, Hohl K et al. 2015. Crystal structure of the human cytomegalovirus pUL50-pUL53 core nuclear egress complex provides insight into a unique assembly scaffold for virus-host protein interactions. J. Biol. Chem. 290:27452–58
    [Google Scholar]
  57. 57.
    Bigalke JM, Heldwein EE. 2015. Structural basis of membrane budding by the nuclear egress complex of herpesviruses. EMBO J. 34:2921–36
    [Google Scholar]
  58. 58.
    Zeev-Ben-Mordehai T, Weberruss M, Lorenz M, Cheleski J, Hellberg T et al. 2015. Crystal structure of the herpesvirus nuclear egress complex provides insights into inner nuclear membrane remodeling. Cell Rep. 13:2645–52
    [Google Scholar]
  59. 59.
    Muller YA, Hage S, Alkhashrom S, Hollriegl T, Weigert S et al. 2020. High-resolution crystal structures of two prototypical β- and γ-herpesvirus nuclear egress complexes unravel the determinants of subfamily specificity. J. Biol. Chem. 295:3189–201
    [Google Scholar]
  60. 60.
    Thorsen MK, Draganova EB, Heldwein EE. 2022. The nuclear egress complex of Epstein-Barr virus buds membranes through an oligomerization-driven mechanism. PLOS Pathog. 18:e1010623
    [Google Scholar]
  61. 61.
    Schweininger J, Kriegel M, Hage S, Conrad M, Alkhashrom S et al. 2022. The crystal structure of the varicella-zoster Orf24-Orf27 nuclear egress complex spotlights multiple determinants of herpesvirus subfamily specificity. J. Biol. Chem. 298:101625
    [Google Scholar]
  62. 62.
    Bigalke JM, Heldwein EE. 2017. Have NEC coat, will travel: structural basis of membrane budding during nuclear egress in herpesviruses. Adv. Virus Res. 97:107–41
    [Google Scholar]
  63. 63.
    Diewald B, Socher E, Soldner CA, Sticht H. 2018. Conformational dynamics of herpesviral NEC proteins in different oligomerization states. Int. J. Mol. Sci. 19:102908
    [Google Scholar]
  64. 64.
    Roller RJ, Bjerke SL, Haugo AC, Hanson S 2010. Analysis of a charge cluster mutation of herpes simplex virus type 1 UL34 and its extragenic suppressor suggests a novel interaction between pUL34 and pUL31 that is necessary for membrane curvature around capsids. J. Virol. 84:3921–34
    [Google Scholar]
  65. 65.
    Roller RJ, Haugo AC, Kopping NJ. 2011. Intragenic and extragenic suppression of a mutation in herpes simplex virus 1 UL34 that affects both nuclear envelope targeting and membrane budding. J. Virol. 85:11615–25
    [Google Scholar]
  66. 66.
    Ronfeldt S, Franzke K, Holper JE, Klupp BG, Mettenleiter TC. 2020. Mutational functional analysis of the pseudorabies virus nuclear egress complex-nucleocapsid interaction. J. Virol. 94:8e01910–19
    [Google Scholar]
  67. 67.
    Ronfeldt S, Klupp BG, Franzke K, Mettenleiter TC. 2017. Lysine 242 within helix 10 of the pseudorabies virus nuclear egress complex pUL31 component is critical for primary envelopment of nucleocapsids. J. Virol. 91:22e01182–17
    [Google Scholar]
  68. 68.
    Schnee M, Ruzsics Z, Bubeck A, Koszinowski UH. 2006. Common and specific properties of herpesvirus UL34/UL31 protein family members revealed by protein complementation assay. J. Virol. 80:11658–66
    [Google Scholar]
  69. 69.
    Marschall M, Muller YA, Diewald B, Sticht H, Milbradt J. 2017. The human cytomegalovirus nuclear egress complex unites multiple functions: recruitment of effectors, nuclear envelope rearrangement, and docking to nuclear capsids. Rev. Med. Virol. 27:4e1934
    [Google Scholar]
  70. 70.
    Leach N, Bjerke SL, Christensen DK, Bouchard JM, Mou F et al. 2007. Emerin is hyperphosphorylated and redistributed in herpes simplex virus type 1-infected cells in a manner dependent on both UL34 and US3. J. Virol. 81:10792–803
    [Google Scholar]
  71. 71.
    Morris JB, Hofemeister H, O'Hare P. 2007. Herpes simplex virus infection induces phosphorylation and delocalization of emerin, a key inner nuclear membrane protein. J. Virol. 81:4429–37
    [Google Scholar]
  72. 72.
    Kopp M, Klupp BG, Granzow H, Fuchs W, Mettenleiter TC. 2002. Identification and characterization of the pseudorabies virus tegument proteins UL46 and UL47: role for UL47 in virion morphogenesis in the cytoplasm. J. Virol. 76:8820–33
    [Google Scholar]
  73. 73.
    Gruenbaum Y, Foisner R. 2015. Lamins: nuclear intermediate filament proteins with fundamental functions in nuclear mechanics and genome regulation. Annu. Rev. Biochem. 84:131–64
    [Google Scholar]
  74. 74.
    Park R, Baines JD. 2006. Herpes simplex virus type 1 infection induces activation and recruitment of protein kinase C to the nuclear membrane and increased phosphorylation of lamin B. J. Virol. 80:494–504
    [Google Scholar]
  75. 75.
    Muranyi W, Haas J, Wagner M, Krohne G, Koszinowski UH. 2002. Cytomegalovirus recruitment of cellular kinases to dissolve the nuclear lamina. Science 297:854–57
    [Google Scholar]
  76. 76.
    Skiba M, Mettenleiter TC, Karger A. 2008. Quantitative whole-cell proteome analysis of pseudorabies virus-infected cells. J. Virol. 82:9689–99
    [Google Scholar]
  77. 77.
    Sutter E, de Oliveira AP, Tobler K, Schraner EM, Sonda S et al. 2012. Herpes simplex virus 1 induces de novo phospholipid synthesis. Virology 429:124–35
    [Google Scholar]
  78. 78.
    Morimoto T, Arii J, Tanaka M, Sata T, Akashi H et al. 2009. Differences in the regulatory and functional effects of the Us3 protein kinase activities of herpes simplex virus 1 and 2. J. Virol. 83:11624–34
    [Google Scholar]
  79. 79.
    Nishiyama Y, Yamada Y, Kurachi R, Daikoku T. 1992. Construction of a US3 lacZ insertion mutant of herpes simplex virus type 2 and characterization of its phenotype in vitro and in vivo. Virology 190:256–68
    [Google Scholar]
  80. 80.
    Sehl J, Portner S, Klupp BG, Granzow H, Franzke K et al. 2020. Roles of the different isoforms of the pseudorabies virus protein kinase pUS3 in nuclear egress. J. Virol. 94:7e02029–19
    [Google Scholar]
  81. 81.
    Longnecker R, Roizman B. 1987. Clustering of genes dispensable for growth in culture in the S component of the HSV-1 genome. Science 236:573–76
    [Google Scholar]
  82. 82.
    Purves FC, Spector D, Roizman B. 1991. The herpes simplex virus 1 protein kinase encoded by the US3 gene mediates posttranslational modification of the phosphoprotein encoded by the UL34 gene. J. Virol. 65:5757–64
    [Google Scholar]
  83. 83.
    Ryckman BJ, Roller RJ. 2004. Herpes simplex virus type 1 primary envelopment: UL34 protein modification and the US3-UL34 catalytic relationship. J. Virol. 78:399–412
    [Google Scholar]
  84. 84.
    Mou F, Wills E, Baines JD. 2009. Phosphorylation of the U(L)31 protein of herpes simplex virus 1 by the U(S)3-encoded kinase regulates localization of the nuclear envelopment complex and egress of nucleocapsids. J. Virol. 83:5181–91
    [Google Scholar]
  85. 85.
    Wisner TW, Wright CC, Kato A, Kawaguchi Y, Mou F et al. 2009. Herpesvirus gB-induced fusion between the virion envelope and outer nuclear membrane during virus egress is regulated by the viral US3 kinase. J. Virol. 83:3115–26
    [Google Scholar]
  86. 86.
    Muradov JH, Finnen RL, Gulak MA, Hay TJM, Banfield BW. 2021. pUL21 regulation of pUs3 kinase activity influences the nature of nuclear envelope deformation by the HSV-2 nuclear egress complex. PLOS Pathog. 17:e1009679
    [Google Scholar]
  87. 87.
    Benedyk TH, Muenzner J, Connor V, Han Y, Brown K et al. 2021. pUL21 is a viral phosphatase adaptor that promotes herpes simplex virus replication and spread. PLOS Pathog. 17:e1009824
    [Google Scholar]
  88. 88.
    Klupp BG, Bottcher S, Granzow H, Kopp M, Mettenleiter TC. 2005. Complex formation between the UL16 and UL21 tegument proteins of pseudorabies virus. J. Virol. 79:1510–22
    [Google Scholar]
  89. 89.
    Baines JD, Koyama AH, Huang T, Roizman B. 1994. The UL21 gene products of herpes simplex virus 1 are dispensable for growth in cultured cells. J. Virol. 68:2929–36
    [Google Scholar]
  90. 90.
    Gao J, Finnen RL, Sherry MR, Le Sage V, Banfield BW 2020. Differentiating the roles of UL16, UL21, and Us3 in the nuclear egress of herpes simplex virus capsids. J. Virol. 94:13e00738–20
    [Google Scholar]
  91. 91.
    Bigalke JM, Heuser T, Nicastro D, Heldwein EE. 2014. Membrane deformation and scission by the HSV-1 nuclear egress complex. Nat. Commun. 5:4131
    [Google Scholar]
  92. 92.
    Lorenz M, Vollmer B, Unsay JD, Klupp BG, Garcia-Saez AJ et al. 2015. A single herpesvirus protein can mediate vesicle formation in the nuclear envelope. J. Biol. Chem. 290:6962–74
    [Google Scholar]
  93. 93.
    Desai PJ, Pryce EN, Henson BW, Luitweiler EM, Cothran J. 2012. Reconstitution of the Kaposi's sarcoma-associated herpesvirus nuclear egress complex and formation of nuclear membrane vesicles by coexpression of ORF67 and ORF69 gene products. J. Virol. 86:594–98
    [Google Scholar]
  94. 94.
    Klupp BG, Granzow H, Fuchs W, Keil GM, Finke S, Mettenleiter TC. 2007. Vesicle formation from the nuclear membrane is induced by coexpression of two conserved herpesvirus proteins. PNAS 104:7241–46
    [Google Scholar]
  95. 95.
    Granzow H, Klupp BG, Fuchs W, Veits J, Osterrieder N, Mettenleiter TC. 2001. Egress of alphaherpesviruses: comparative ultrastructural study. J. Virol. 75:3675–84
    [Google Scholar]
  96. 96.
    Draganova EB, Zhang J, Zhou ZH, Heldwein EE. 2020. Structural basis for capsid recruitment and coat formation during HSV-1 nuclear egress. eLife 9:e56627
    [Google Scholar]
  97. 97.
    Vu A, White S, Cassmann T, Roller RJ. 2021. Herpes simplex virus 1 UL34 mutants that affect membrane budding regulation and nuclear lamina disruption. J. Virol. 95:e0087321
    [Google Scholar]
  98. 98.
    Takeshima K, Arii J, Maruzuru Y, Koyanagi N, Kato A, Kawaguchi Y. 2019. Identification of the capsid binding site in the herpes simplex virus 1 nuclear egress complex and its role in viral primary envelopment and replication. J. Virol. 93:21e01290–19
    [Google Scholar]
  99. 99.
    Padula ME, Sydnor ML, Wilson DW. 2009. Isolation and preliminary characterization of herpes simplex virus 1 primary enveloped virions from the perinuclear space. J. Virol. 83:4757–65
    [Google Scholar]
  100. 100.
    Sucharita S, Zhang K, van Drunen Littel-van den Hurk S. 2021. VP8, the major tegument protein of bovine herpesvirus-1, is partially packaged during early tegument formation in a VP22-dependent manner. Viruses 13:91854
    [Google Scholar]
  101. 101.
    Abaitua F, Hollinshead M, Bolstad M, Crump CM, O'Hare P. 2012. A nuclear localization signal in herpesvirus protein VP1-2 is essential for infection via capsid routing to the nuclear pore. J. Virol. 86:8998–9014
    [Google Scholar]
  102. 102.
    Mohl BS, Bottcher S, Granzow H, Kuhn J, Klupp BG, Mettenleiter TC. 2009. Intracellular localization of the pseudorabies virus large tegument protein pUL36. J. Virol. 83:9641–51
    [Google Scholar]
  103. 103.
    Radtke K, Kieneke D, Wolfstein A, Michael K, Steffen W et al. 2010. Plus- and minus-end directed microtubule motors bind simultaneously to herpes simplex virus capsids using different inner tegument structures. PLOS Pathog. 6:e1000991
    [Google Scholar]
  104. 104.
    Luxton GW, Lee JI, Haverlock-Moyns S, Schober JM, Smith GA. 2006. The pseudorabies virus VP1/2 tegument protein is required for intracellular capsid transport. J. Virol. 80:201–9
    [Google Scholar]
  105. 105.
    Desai PJ. 2000. A null mutation in the UL36 gene of herpes simplex virus type 1 results in accumulation of unenveloped DNA-filled capsids in the cytoplasm of infected cells. J. Virol. 74:11608–18
    [Google Scholar]
  106. 106.
    Fuchs W, Klupp BG, Granzow H, Mettenleiter TC. 2004. Essential function of the pseudorabies virus UL36 gene product is independent of its interaction with the UL37 protein. J. Virol. 78:11879–89
    [Google Scholar]
  107. 107.
    Klupp B, Altenschmidt J, Granzow H, Fuchs W, Mettenleiter TC. 2008. Glycoproteins required for entry are not necessary for egress of pseudorabies virus. J. Virol. 82:6299–309
    [Google Scholar]
  108. 108.
    Vallbracht M, Backovic M, Klupp BG, Rey FA, Mettenleiter TC. 2019. Common characteristics and unique features: a comparison of the fusion machinery of the alphaherpesviruses Pseudorabies virus and Herpes simplex virus. Adv. Virus Res. 104:225–281
    [Google Scholar]
  109. 109.
    Vallbracht M, Lotzsch H, Klupp BG, Fuchs W, Vollmer B et al. 2021. In vitro viral evolution identifies a critical residue in the alphaherpesvirus fusion glycoprotein B ectodomain that controls gH/gL-independent entry. mBio 12:3e00557–21
    [Google Scholar]
  110. 110.
    Galdiero S, Falanga A, Vitiello M, Browne H, Pedone C, Galdiero M. 2005. Fusogenic domains in herpes simplex virus type 1 glycoprotein H. J. Biol. Chem. 280:28632–43
    [Google Scholar]
  111. 111.
    Farnsworth A, Wisner TW, Webb M, Roller R, Cohen G et al. 2007. Herpes simplex virus glycoproteins gB and gH function in fusion between the virion envelope and the outer nuclear membrane. PNAS 104:10187–92
    [Google Scholar]
  112. 112.
    Peeters B, de Wind N, Hooisma M, Wagenaar F, Gielkens A, Moormann R. 1992. Pseudorabies virus envelope glycoproteins gp50 and gII are essential for virus penetration, but only gII is involved in membrane fusion. J. Virol. 66:894–905
    [Google Scholar]
  113. 113.
    Hutchinson L, Johnson DC. 1995. Herpes simplex virus glycoprotein K promotes egress of virus particles. J. Virol. 69:5401–13
    [Google Scholar]
  114. 114.
    Melancon JM, Luna RE, Foster TP, Kousoulas KG. 2005. Herpes simplex virus type 1 gK is required for gB-mediated virus-induced cell fusion, while neither gB and gK nor gB and UL20p function redundantly in virion de-envelopment. J. Virol. 79:299–313
    [Google Scholar]
  115. 115.
    Fuchs W, Klupp BG, Granzow H, Mettenleiter TC. 1997. The UL20 gene product of pseudorabies virus functions in virus egress. J. Virol. 71:5639–46
    [Google Scholar]
  116. 116.
    Klupp BG, Baumeister J, Dietz P, Granzow H, Mettenleiter TC. 1998. Pseudorabies virus glycoprotein gK is a virion structural component involved in virus release but is not required for entry. J. Virol. 72:1949–58
    [Google Scholar]
  117. 117.
    Butt BG, Owen DJ, Jeffries CM, Ivanova L, Hill CH et al. 2020. Insights into herpesvirus assembly from the structure of the pUL7:pUL51 complex. eLife 9:e53789
    [Google Scholar]
  118. 118.
    Sosa BA, Kutay U, Schwartz TU. 2013. Structural insights into LINC complexes. Curr. Opin. Struct. Biol. 23:285–91
    [Google Scholar]
  119. 119.
    Rothballer A, Schwartz TU, Kutay U. 2013. LINCing complex functions at the nuclear envelope: what the molecular architecture of the LINC complex can reveal about its function. Nucleus 4:29–36
    [Google Scholar]
  120. 120.
    Buchkovich NJ, Maguire TG, Alwine JC. 2010. Role of the endoplasmic reticulum chaperone BiP, SUN domain proteins, and dynein in altering nuclear morphology during human cytomegalovirus infection. J. Virol. 84:7005–17
    [Google Scholar]
  121. 121.
    Klupp BG, Hellberg T, Granzow H, Franzke K, Dominguez Gonzalez B et al. 2017. Integrity of the linker of nucleoskeleton and cytoskeleton is required for efficient herpesvirus nuclear egress. J. Virol. 91:19e00330–17
    [Google Scholar]
  122. 122.
    Cruz-Palomar K, Hawkins J, Vandal C, Quenneville J, Gagnon E, Lippe R. 2022. SUN2 modulates the propagation of HSV-1. J. Virol. 96:e0045322
    [Google Scholar]
  123. 123.
    Rampello AJ, Prophet SM, Schlieker C. 2020. The role of torsin AAA+ proteins in preserving nuclear envelope integrity and safeguarding against disease. Biomolecules 10:3468
    [Google Scholar]
  124. 124.
    Goodchild RE, Kim CE, Dauer WT. 2005. Loss of the dystonia-associated protein torsinA selectively disrupts the neuronal nuclear envelope. Neuron 48:923–32
    [Google Scholar]
  125. 125.
    Atai NA, Ryan SD, Kothary R, Breakefield XO, Nery FC. 2012. Untethering the nuclear envelope and cytoskeleton: biologically distinct dystonias arising from a common cellular dysfunction. Int. J. Cell Biol. 2012:634214
    [Google Scholar]
  126. 126.
    Turner EM, Brown RS, Laudermilch E, Tsai PL, Schlieker C. 2015. The torsin activator LULL1 is required for efficient growth of herpes simplex virus 1. J. Virol. 89:8444–52
    [Google Scholar]
  127. 127.
    Holper JE, Klupp BG, Luxton GWG, Franzke K, Mettenleiter TC. 2020. Function of torsin AAA+ ATPases in pseudorabies virus nuclear egress. Cells 9:3738
    [Google Scholar]
  128. 128.
    Lev S, Ben Halevy D, Peretti D, Dahan N 2008. The VAP protein family: from cellular functions to motor neuron disease. Trends Cell Biol. 18:282–90
    [Google Scholar]
  129. 129.
    Saiz-Ros N, Czapiewski R, Epifano I, Stevenson A, Swanson SK et al. 2019. Host vesicle fusion protein VAPB contributes to the nuclear egress stage of herpes simplex virus type-1 (HSV-1) replication. Cells 8:2120
    [Google Scholar]
  130. 130.
    Dorsch AD, Holper JE, Franzke K, Zaeck LM, Mettenleiter TC, Klupp BG. 2021. Role of vesicle-associated membrane protein-associated proteins (VAP) A and VAPB in nuclear egress of the alphaherpesvirus pseudorabies virus. Viruses 13:61117
    [Google Scholar]
  131. 131.
    Olmos Y. 2022. The ESCRT machinery: remodeling, repairing, and sealing membranes. Membranes 12:6633
    [Google Scholar]
  132. 132.
    Rose KM. 2021. When in need of an ESCRT: The nature of virus assembly sites suggests mechanistic parallels between nuclear virus egress and retroviral budding. Viruses 13:61138
    [Google Scholar]
  133. 133.
    Crump CM, Yates C, Minson T. 2007. Herpes simplex virus type 1 cytoplasmic envelopment requires functional Vps4. J. Virol. 81:7380–87
    [Google Scholar]
  134. 134.
    Pawliczek T, Crump CM. 2009. Herpes simplex virus type 1 production requires a functional ESCRT-III complex but is independent of TSG101 and ALIX expression. J. Virol. 83:11254–64
    [Google Scholar]
  135. 135.
    Tandon R, AuCoin DP, Mocarski ES. 2009. Human cytomegalovirus exploits ESCRT machinery in the process of virion maturation. J. Virol. 83:10797–807
    [Google Scholar]
  136. 136.
    Streck NT, Carmichael J, Buchkovich NJ. 2018. Nonenvelopment role for the ESCRT-III complex during human cytomegalovirus infection. J. Virol. 92:12e02096–17
    [Google Scholar]
  137. 137.
    Fraile-Ramos A, Pelchen-Matthews A, Risco C, Rejas MT, Emery VC et al. 2007. The ESCRT machinery is not required for human cytomegalovirus envelopment. Cell. Microbiol. 9:2955–67
    [Google Scholar]
  138. 138.
    Lee CP, Liu PT, Kung HN, Su MT, Chua HH et al. 2012. The ESCRT machinery is recruited by the viral BFRF1 protein to the nucleus-associated membrane for the maturation of Epstein-Barr virus. PLOS Pathog. 8:e1002904
    [Google Scholar]
  139. 139.
    Arii J, Watanabe M, Maeda F, Tokai-Nishizumi N, Chihara T et al. 2018. ESCRT-III mediates budding across the inner nuclear membrane and regulates its integrity. Nat. Commun. 9:3379
    [Google Scholar]
  140. 140.
    Kharkwal H, Smith CG, Wilson DW. 2014. Blocking ESCRT-mediated envelopment inhibits microtubule-dependent trafficking of alphaherpesviruses in vitro. J. Virol. 88:14467–78
    [Google Scholar]
  141. 141.
    Hirohata Y, Arii J, Liu Z, Shindo K, Oyama M et al. 2015. Herpes simplex virus 1 recruits CD98 heavy chain and β1 integrin to the nuclear membrane for viral de-envelopment. J. Virol. 89:7799–812
    [Google Scholar]
  142. 142.
    Egusquiza-Alvarez CA, Robles-Flores M. 2022. An approach to p32/gC1qR/HABP1: a multifunctional protein with an essential role in cancer. J. Cancer Res. Clin. Oncol. 148:1831–54
    [Google Scholar]
  143. 143.
    Milbradt J, Kraut A, Hutterer C, Sonntag E, Schmeiser C et al. 2014. Proteomic analysis of the multimeric nuclear egress complex of human cytomegalovirus. Mol. Cell. Proteom. 13:2132–46
    [Google Scholar]
  144. 144.
    Liu Z, Kato A, Oyama M, Kozuka-Hata H, Arii J, Kawaguchi Y. 2015. Role of host cell p32 in herpes simplex virus 1 de-envelopment during viral nuclear egress. J. Virol. 89:8982–98
    [Google Scholar]
  145. 145.
    Wang Y, Yang Y, Wu S, Pan S, Zhou C et al. 2014. p32 is a novel target for viral protein ICP34.5 of herpes simplex virus type 1 and facilitates viral nuclear egress. J. Biol. Chem. 289:35795–805
    [Google Scholar]
  146. 146.
    Anand D, Chaudhuri A. 2022. Grease in the nucleus: insights into the dynamic life of nuclear membranes. J. Membr. Biol. 4:1–9
    [Google Scholar]
  147. 147.
    Larijani B, Pytowski L, Vaux DJ. 2022. The enigma of phosphoinositides and their derivatives: their role in regulation of subcellular compartment morphology. Biochim. Biophys. Acta Biomembr. 1864:183780
    [Google Scholar]
  148. 148.
    Grimm KS, Klupp BG, Granzow H, Muller FM, Fuchs W, Mettenleiter TC. 2012. Analysis of viral and cellular factors influencing herpesvirus-induced nuclear envelope breakdown. J. Virol. 86:6512–21
    [Google Scholar]
  149. 149.
    Schulz KS, Klupp BG, Granzow H, Mettenleiter TC. 2013. Glycoproteins gB and gH are required for syncytium formation but not for herpesvirus-induced nuclear envelope breakdown. J. Virol. 87:9733–41
    [Google Scholar]
  150. 150.
    Panagaki D, Croft JT, Keuenhof K, Larsson Berglund L, Andersson S et al. 2021. Nuclear envelope budding is a response to cellular stress. PNAS 118:30e2020997118
    [Google Scholar]
  151. 151.
    Fradkin LG, Budnik V. 2016. This bud's for you: mechanisms of cellular nucleocytoplasmic trafficking via nuclear envelope budding. Curr. Opin. Cell Biol. 41:125–31
    [Google Scholar]
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