1887

Abstract

Herpes simplex virus type 1 (HSV-1) capsids assemble in the nucleus but acquire their teguments from various cellular compartments. Unfortunately, little is known about their exact arrangement and when they coat the newly produced capsids. The complexity of the virions is further highlighted by our recent proteomics analysis that detected the presence of several novel or controversial components in extracellular HSV-1 virions. The present study probes the localization and linkage to the virus particles of some of these incorporated proteins. We confirm the recently reported tight association of infected cell polypeptide (ICP)0 with the capsid and show that this property extends to ICP4. We also confirm our proteomics data and show biochemically that UL7 and UL23 are indeed mature virion tegument components that, unlike ICP0 and ICP4, are salt-extractable. Interestingly, treatment with -ethylmaleimide, which covalently modifies reduced cysteines, strongly prevented the release of UL7 and UL23 by salts, but did not perturb the interactions of ICP0 and ICP4 with the virus particles. This hitheir at distinct biochemical properties of the virion constituents and the selective implication of reduced cysteines in their organization and dynamics. Finally, the data revealed, by two independent means, the presence of ICP0 and ICP4 on intranuclear capsids, consistent with the possibility that they may at least partially be recruited to the virus particles early on. These findings add significantly to our understanding of HSV-1 virion assembly and to the debate about the incorporation of ICP0 and ICP4 in virus particles.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.039776-0
2012-03-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/93/3/624.html?itemId=/content/journal/jgv/10.1099/vir.0.039776-0&mimeType=html&fmt=ahah

References

  1. Bechtel J. T., Winant R. C., Ganem D. 2005; Host and viral proteins in the virion of Kaposi’s sarcoma-associated herpesvirus. J Virol 79:4952–4964 [View Article][PubMed]
    [Google Scholar]
  2. Bergman A.-C., Nyman P. O., Larsson G. 1998; Kinetic properties and stereospecificity of the monomeric dUTPase from herpes simplex virus type 1. FEBS Lett 441:327–330 [View Article][PubMed]
    [Google Scholar]
  3. Bjerke S. L., Roller R. J. 2006; Roles for herpes simplex virus type 1 UL34 and US3 proteins in disrupting the nuclear lamina during herpes simplex virus type 1 egress. Virology 347:261–276 [View Article][PubMed]
    [Google Scholar]
  4. Björnberg O., Bergman A. C., Rosengren A. M., Persson R., Lehman I. R., Nyman P. O. 1993; dUTPase from herpes simplex virus type 1; purification from infected green monkey kidney (Vero) cells and from an overproducing Escherichia coli strain. Protein Expr Purif 4:149–159 [View Article][PubMed]
    [Google Scholar]
  5. Boehmer P. E., Lehman I. R. 1997; Herpes simplex virus DNA replication. Annu Rev Biochem 66:347–384 [View Article][PubMed]
    [Google Scholar]
  6. Bucks M. A., O’Regan K. J., Murphy M. A., Wills J. W., Courtney R. J. 2007; Herpes simplex virus type 1 tegument proteins VP1/2 and UL37 are associated with intranuclear capsids. Virology 361:316–324 [View Article][PubMed]
    [Google Scholar]
  7. Bulaj G., Kortemme T., Goldenberg D. P. 1998; Ionization-reactivity relationships for cysteine thiols in polypeptides. Biochemistry 37:8965–8972 [View Article][PubMed]
    [Google Scholar]
  8. Coppock D. L., Pardee A. B. 1987; Control of thymidine kinase mRNA during the cell cycle. Mol Cell Biol 7:2925–2932[PubMed]
    [Google Scholar]
  9. Delboy M. G., Nicola A. V. 2011; A pre-immediate-early role for tegument ICP0 in the proteasome-dependent entry of herpes simplex virus. J Virol 85:5910–5918 [View Article][PubMed]
    [Google Scholar]
  10. Delboy M. G., Siekavizza-Robles C. R., Nicola A. V. 2010; Herpes simplex virus tegument ICP0 is capsid associated, and its E3 ubiquitin ligase domain is important for incorporation into virions. J Virol 84:1637–1640 [View Article][PubMed]
    [Google Scholar]
  11. Döhner K., Wolfstein A., Prank U., Echeverri C., Dujardin D., Vallee R., Sodeik B. 2002; Function of dynein and dynactin in herpes simplex virus capsid transport. Mol Biol Cell 13:2795–2809 [View Article][PubMed]
    [Google Scholar]
  12. Donnelly M., Elliott G. 2001; Nuclear localization and shuttling of herpes simplex virus tegument protein VP13/14. J Virol 75:2566–2574 [View Article][PubMed]
    [Google Scholar]
  13. Dry I., Haig D. M., Inglis N. F., Imrie L., Stewart J. P., Russell G. C. 2008; Proteomic analysis of pathogenic and attenuated alcelaphine herpesvirus 1. J Virol 82:5390–5397 [View Article][PubMed]
    [Google Scholar]
  14. Elliott G., Hafezi W., Whiteley A., Bernard E. 2005; Deletion of the herpes simplex virus VP22-encoding gene (UL49) alters the expression, localization, and virion incorporation of ICP0. J Virol 79:9735–9745 [View Article][PubMed]
    [Google Scholar]
  15. Everett R. D. 2000; ICP0, a regulator of herpes simplex virus during lytic and latent infection. Bioessays 22:761–770 [View Article][PubMed]
    [Google Scholar]
  16. Fuchs W., Granzow H., Klopfleisch R., Klupp B. G., Rosenkranz D., Mettenleiter T. C. 2005; The UL7 gene of pseudorabies virus encodes a nonessential structural protein which is involved in virion formation and egress. J Virol 79:11291–11299 [View Article][PubMed]
    [Google Scholar]
  17. Geoffroy M. C., Epstein A. L., Toublanc E., Moullier P., Salvetti A. 2004; Herpes simplex virus type 1 ICP0 protein mediates activation of adeno-associated virus type 2 rep gene expression from a latent integrated form. J Virol 78:10977–10986 [View Article][PubMed]
    [Google Scholar]
  18. Greber U. F., Webster P., Weber J., Helenius A. 1996; The role of the adenovirus protease on virus entry into cells. EMBO J 15:1766–1777[PubMed]
    [Google Scholar]
  19. Guo H., Shen S., Wang L., Deng H. 2010; Role of tegument proteins in herpesvirus assembly and egress. Protein Cell 1:987–998 [View Article][PubMed]
    [Google Scholar]
  20. Hwang S., Kim K. S., Flano E., Wu T. T., Tong L. M., Park A. N., Song M. J., Sanchez D. J., O’Connell R. M.other authors 2009; Conserved herpesviral kinase promotes viral persistence by inhibiting the IRF-3-mediated type I interferon response. Cell Host Microbe 5:166–178 [View Article][PubMed]
    [Google Scholar]
  21. Johannsen E., Luftig M., Chase M. R., Weicksel S., Cahir-McFarland E., Illanes D., Sarracino D., Kieff E. 2004; Proteins of purified Epstein–Barr virus. Proc Natl Acad Sci U S A 101:16286–16291 [View Article][PubMed]
    [Google Scholar]
  22. Jöns A., Mettenleiter T. C. 1996; Identification and characterization of pseudorabies virus dUTPase. J Virol 70:1242–1245[PubMed]
    [Google Scholar]
  23. Kalamvoki M., Roizman B. 2010; Role of herpes simplex virus ICP0 in the transactivation of genes introduced by infection or transfection: a reappraisal. J Virol 84:4222–4228 [View Article][PubMed]
    [Google Scholar]
  24. Kalamvoki M., Qu J., Roizman B. 2008; Translocation and colocalization of ICP4 and ICP0 in cells infected with herpes simplex virus 1 mutants lacking glycoprotein E, glycoprotein I, or the virion host shutoff product of the UL41 gene. J Virol 82:1701–1713 [View Article][PubMed]
    [Google Scholar]
  25. Kelly B. J., Fraefel C., Cunningham A. L., Diefenbach R. J. 2009; Functional roles of the tegument proteins of herpes simplex virus type 1. Virus Res 145:173–186 [View Article][PubMed]
    [Google Scholar]
  26. Kramer T., Greco T. M., Enquist L. W., Cristea I. M. 2011; Proteomic characterization of pseudorabies virus extracellular virions. J Virol 85:6427–6441 [View Article][PubMed]
    [Google Scholar]
  27. Lamberti C., Weller S. K. 1998; The herpes simplex virus type 1 cleavage/packaging protein, UL32, is involved in efficient localization of capsids to replication compartments. J Virol 72:2463–2473[PubMed]
    [Google Scholar]
  28. Lee J. H., Vittone V., Diefenbach E., Cunningham A. L., Diefenbach R. J. 2008; Identification of structural protein–protein interactions of herpes simplex virus type 1. Virology 378:347–354 [View Article][PubMed]
    [Google Scholar]
  29. Leopardi R., Van Sant C., Roizman B. 1997; The herpes simplex virus 1 protein kinase US3 is required for protection from apoptosis induced by the virus. Proc Natl Acad Sci U S A 94:7891–7896 [View Article][PubMed]
    [Google Scholar]
  30. Liashkovich I., Hafezi W., Kühn J. M., Oberleithner H., Shahin V. 2011; Nuclear delivery mechanism of herpes simplex virus type 1 genome. J Mol Recognit 24:414–421 [View Article][PubMed]
    [Google Scholar]
  31. Loret S., Guay G., Lippé R. 2008; Comprehensive characterization of extracellular herpes simplex virus type 1 virions. J Virol 82:8605–8618 [View Article][PubMed]
    [Google Scholar]
  32. Maringer K., Elliott G. 2010; Recruitment of herpes simplex virus type 1 immediate-early protein ICP0 to the virus particle. J Virol 84:4682–4696 [View Article][PubMed]
    [Google Scholar]
  33. McCombs R. M., Williams G. A. 1973; Disruption of herpes virus nucleocapsids using lithium iodide, guanidine and mercaptoethanol. J Gen Virol 20:395–400 [View Article][PubMed]
    [Google Scholar]
  34. Meckes D. G. Jr, Wills J. W. 2007; Dynamic interactions of the UL16 tegument protein with the capsid of herpes simplex virus. J Virol 81:13028–13036 [View Article][PubMed]
    [Google Scholar]
  35. Meckes D. G. Jr, Wills J. W. 2008; Structural rearrangement within an enveloped virus upon binding to the host cell. J Virol 82:10429–10435 [View Article][PubMed]
    [Google Scholar]
  36. Mettenleiter T. C. 2002; Herpesvirus assembly and egress. J Virol 76:1537–1547 [View Article][PubMed]
    [Google Scholar]
  37. Mettenleiter T. C. 2004; Budding events in herpesvirus morphogenesis. Virus Res 106:167–180 [View Article][PubMed]
    [Google Scholar]
  38. Mettenleiter T. C. 2006; Intriguing interplay between viral proteins during herpesvirus assembly or: the herpesvirus assembly puzzle. Vet Microbiol 113:163–169 [View Article][PubMed]
    [Google Scholar]
  39. Mettenleiter T. C., Klupp B. G., Granzow H. 2006; Herpesvirus assembly: a tale of two membranes. Curr Opin Microbiol 9:423–429 [View Article][PubMed]
    [Google Scholar]
  40. Mettenleiter T. C., Klupp B. G., Granzow H. 2009; Herpesvirus assembly: an update. Virus Res 143:222–234 [View Article][PubMed]
    [Google Scholar]
  41. Morcock D. R., Thomas J. A., Gagliardi T. D., Gorelick R. J., Roser J. D., Chertova E. N., Bess J. W. Jr, Ott D. E., Sattentau Q. J.other authors 2005; Elimination of retroviral infectivity by N-ethylmaleimide with preservation of functional envelope glycoproteins. J Virol 79:1533–1542 [View Article][PubMed]
    [Google Scholar]
  42. Mou F., Forest T., Baines J. D. 2007; US3 of herpes simplex virus type 1 encodes a promiscuous protein kinase that phosphorylates and alters localization of lamin A/C in infected cells. J Virol 81:6459–6470 [View Article][PubMed]
    [Google Scholar]
  43. Munch-Petersen B., Cloos L., Jensen H. K., Tyrsted G. 1995; Human thymidine kinase 1. Regulation in normal and malignant cells. Adv Enzyme Regul 35:69–89 [View Article][PubMed]
    [Google Scholar]
  44. Nagahara N., Matsumura T., Okamoto R., Kajihara Y. 2009; Protein cysteine modifications: (2) reactivity specificity and topics of medicinal chemistry and protein engineering. Curr Med Chem 16:4490–4501 [View Article][PubMed]
    [Google Scholar]
  45. Newcomb W. W., Brown J. C. 2009; Time-dependent transformation of the herpesvirus tegument. J Virol 83:8082–8089 [View Article][PubMed]
    [Google Scholar]
  46. Newcomb W. W., Homa F. L., Thomsen D. R., Ye Z., Brown J. C. 1994; Cell-free assembly of the herpes simplex virus capsid. J Virol 68:6059–6063[PubMed]
    [Google Scholar]
  47. Newcomb W. W., Homa F. L., Brown J. C. 2006; Herpes simplex virus capsid structure: DNA packaging protein UL25 is located on the external surface of the capsid near the vertices. J Virol 80:6286–6294 [View Article][PubMed]
    [Google Scholar]
  48. Ogg P. D., McDonell P. J., Ryckman B. J., Knudson C. M., Roller R. J. 2004; The HSV-1 Us3 protein kinase is sufficient to block apoptosis induced by overexpression of a variety of Bcl-2 family members. Virology 319:212–224 [View Article][PubMed]
    [Google Scholar]
  49. Ojala P. M., Sodeik B., Ebersold M. W., Kutay U., Helenius A. 2000; Herpes simplex virus type 1 entry into host cells: reconstitution of capsid binding and uncoating at the nuclear pore complex in vitro. Mol Cell Biol 20:4922–4931 [View Article][PubMed]
    [Google Scholar]
  50. Orvedahl A., Alexander D., Tallóczy Z., Sun Q., Wei Y., Zhang W., Burns D., Leib D. A., Levine B. 2007; HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein. Cell Host Microbe 1:23–35 [View Article][PubMed]
    [Google Scholar]
  51. Pinter A., Kopelman R., Li Z., Kayman S. C., Sanders D. A. 1997; Localization of the labile disulfide bond between SU and TM of the murine leukemia virus envelope protein complex to a highly conserved CWLC motif in SU that resembles the active-site sequence of thiol-disulfide exchange enzymes. J Virol 71:8073–8077[PubMed]
    [Google Scholar]
  52. Radtke K., Kieneke D., Wolfstein A., Michael K., Steffen W., Scholz T., Karger A., Sodeik B. 2010; Plus- and minus-end directed microtubule motors bind simultaneously to herpes simplex virus capsids using different inner tegument structures. PLoS Pathog 6:e1000991 [View Article][PubMed]
    [Google Scholar]
  53. Rémillard-Labrosse G., Guay G., Lippé R. 2006; Reconstitution of herpes simplex virus type 1 nuclear capsid egress in vitro. J Virol 80:9741–9753 [View Article][PubMed]
    [Google Scholar]
  54. Ren Y., Bell S., Zenner H. L., Lau S.-Y. K., Crump C. M. 2012; Glycoprotein M is important for the efficient incorporation of glycoprotein H–L into herpes simplex virus type 1 particles. J Gen Virol 93:319–329 [View Article][PubMed]
    [Google Scholar]
  55. Roizman B., Gu H., Mandel G. 2005; The first 30 minutes in the life of a virus: unREST in the nucleus. Cell Cycle 4:1019–1021 [View Article][PubMed]
    [Google Scholar]
  56. Roller R. J., Zhou Y., Schnetzer R., Ferguson J., DeSalvo D. 2000; Herpes simplex virus type 1 U(L)34 gene product is required for viral envelopment. J Virol 74:117–129 [View Article][PubMed]
    [Google Scholar]
  57. Ruyechan W. T. 1988; N-Ethylmaleimide inhibition of the DNA-binding activity of the herpes simplex virus type 1 major DNA-binding protein. J Virol 62:810–817[PubMed]
    [Google Scholar]
  58. Salmon B., Cunningham C., Davison A. J., Harris W. J., Baines J. D. 1998; The herpes simplex virus type 1 U(L)17 gene encodes virion tegument proteins that are required for cleavage and packaging of viral DNA. J Virol 72:3779–3788[PubMed]
    [Google Scholar]
  59. Scholtes L. D., Yang K., Li L. X., Baines J. D. 2010; The capsid protein encoded by U(L)17 of herpes simplex virus 1 interacts with tegument protein VP13/14. J Virol 84:7642–7650 [View Article][PubMed]
    [Google Scholar]
  60. Sedlackova L., Rice S. A. 2008; Herpes simplex virus type 1 immediate-early protein ICP27 is required for efficient incorporation of ICP0 and ICP4 into virions. J Virol 82:268–277 [View Article][PubMed]
    [Google Scholar]
  61. Sevier C. S., Kaiser C. A. 2002; Formation and transfer of disulphide bonds in living cells. Nat Rev Mol Cell Biol 3:836–847 [View Article][PubMed]
    [Google Scholar]
  62. Shanda S. K., Wilson D. W. 2008; UL36p is required for efficient transport of membrane-associated herpes simplex virus type 1 along microtubules. J Virol 82:7388–7394 [View Article][PubMed]
    [Google Scholar]
  63. Sheaffer A. K., Newcomb W. W., Brown J. C., Gao M., Weller S. K., Tenney D. J. 2000; Evidence for controlled incorporation of herpes simplex virus type 1 UL26 protease into capsids. J Virol 74:6838–6848 [View Article][PubMed]
    [Google Scholar]
  64. Skepper J. N., Whiteley A., Browne H., Minson A. 2001; Herpes simplex virus nucleocapsids mature to progeny virions by an envelopment → deenvelopment → reenvelopment pathway. J Virol 75:5697–5702 [View Article][PubMed]
    [Google Scholar]
  65. Smiley J. R. 2004; Herpes simplex virus virion host shutoff protein: immune evasion mediated by a viral RNase?. J Virol 78:1063–1068 [View Article][PubMed]
    [Google Scholar]
  66. Smith G. A., Enquist L. W. 2002; Break ins and break outs: viral interactions with the cytoskeleton of mammalian cells. Annu Rev Cell Dev Biol 18:135–161 [View Article][PubMed]
    [Google Scholar]
  67. Sodeik B., Ebersold M. W., Helenius A. 1997; Microtubule-mediated transport of incoming herpes simplex virus 1 capsids to the nucleus. J Cell Biol 136:1007–1021 [View Article][PubMed]
    [Google Scholar]
  68. Stackpole C. W. 1969; Herpes-type virus of the frog renal adenocarcinoma. I. Virus development in tumor transplants maintained at low temperature. J Virol 4:75–93[PubMed]
    [Google Scholar]
  69. Szczepaniak R., Nellissery J., Jadwin J. A., Makhov A. M., Kosinski A., Conway J. F., Weller S. K. 2011; Disulfide bond formation contributes to herpes simplex virus capsid stability and retention of pentons. J Virol 85:8625–8634 [View Article][PubMed]
    [Google Scholar]
  70. Tanaka M., Sata T., Kawaguchi Y. 2008; The product of the Herpes simplex virus 1 UL7 gene interacts with a mitochondrial protein, adenine nucleotide translocator 2. Virol J 5:125 [View Article][PubMed]
    [Google Scholar]
  71. Tatman J. D., Preston V. G., Nicholson P., Elliott R. M., Rixon F. J. 1994; Assembly of herpes simplex virus type 1 capsids using a panel of recombinant baculoviruses. J Gen Virol 75:1101–1113 [View Article][PubMed]
    [Google Scholar]
  72. Trgovcich J., Johnson D., Roizman B. 2002; Cell surface major histocompatibility complex class II proteins are regulated by the products of the γ134.5 and UL41 genes of herpes simplex virus 1. J Virol 76:6974–6986 [View Article][PubMed]
    [Google Scholar]
  73. Turcotte S., Letellier J., Lippé R. 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 [View Article][PubMed]
    [Google Scholar]
  74. Vittone V., Diefenbach E., Triffett D., Douglas M. W., Cunningham A. L., Diefenbach R. J. 2005; Determination of interactions between tegument proteins of herpes simplex virus type 1. J Virol 79:9566–9571 [View Article][PubMed]
    [Google Scholar]
  75. Wolfstein A., Nagel C. H., Radtke K., Döhner K., Allan V. J., Sodeik B. 2006; The inner tegument promotes herpes simplex virus capsid motility along microtubules in vitro. Traffic 7:227–237 [View Article][PubMed]
    [Google Scholar]
  76. Wurth C., Thomas R. M., Folkers G., Scapozza L. 2001; Folding and self-assembly of herpes simplex virus type 1 thymidine kinase. J Mol Biol 313:657–670 [View Article][PubMed]
    [Google Scholar]
  77. Wysocka J., Herr W. 2003; The herpes simplex virus VP16-induced complex: the makings of a regulatory switch. Trends Biochem Sci 28:294–304 [View Article][PubMed]
    [Google Scholar]
  78. Yang T. Y., Courtney R. J. 1995; Influence of the host cell on the association of ICP4 and ICP0 with herpes simplex virus type 1. Virology 211:209–217 [View Article][PubMed]
    [Google Scholar]
  79. Yang C. C., Yang Y. Y., Lin K. L., Lin S. J. 2000; Different forms of HSV-1 VP22a within purified virion and infected cells. J Microbiol Immunol Infect 33:141–148[PubMed]
    [Google Scholar]
  80. Yao F., Courtney R. J. 1989; A major transcriptional regulatory protein (ICP4) of herpes simplex virus type 1 is associated with purified virions. J Virol 63:3338–3344[PubMed]
    [Google Scholar]
  81. Yao F., Courtney R. J. 1991; Association of a major transcriptional regulatory protein, ICP4, of herpes simplex virus type 1 with the plasma membrane of virus-infected cells. J Virol 65:1516–1524[PubMed]
    [Google Scholar]
  82. Yao F., Courtney R. J. 1992; Association of ICP0 but not ICP27 with purified virions of herpes simplex virus type 1. J Virol 66:2709–2716[PubMed]
    [Google Scholar]
  83. Yedowitz J. C., Kotsakis A., Schlegel E. F., Blaho J. A. 2005; Nuclear localizations of the herpes simplex virus type 1 tegument proteins VP13/14, vhs, and VP16 precede VP22-dependent microtubule reorganization and VP22 nuclear import. J Virol 79:4730–4743 [View Article][PubMed]
    [Google Scholar]
  84. Yeh P. C., Meckes D. G. Jr, Wills J. W. 2008; Analysis of the interaction between the UL11 and UL16 tegument proteins of herpes simplex virus. J Virol 82:10693–10700 [View Article][PubMed]
    [Google Scholar]
  85. Yu D., Weller S. K. 1998; Herpes simplex virus type 1 cleavage and packaging proteins UL15 and UL28 are associated with B but not C capsids during packaging. J Virol 72:7428–7439[PubMed]
    [Google Scholar]
  86. Zhu F. X., Chong J. M., Wu L., Yuan Y. 2005; Virion proteins of Kaposi’s sarcoma-associated herpesvirus. J Virol 79:800–811 [View Article][PubMed]
    [Google Scholar]
  87. Zweig M., Heilman C. J. Jr, Hampar B. 1979; Identification of disulfide-linked protein complexes in the nucleocapsids of herpes simplex virus type 2. Virology 94:442–450 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.039776-0
Loading
/content/journal/jgv/10.1099/vir.0.039776-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error