Home LiteratureArticle Details
PMID: 12970444 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Human cytomegalovirus UL99-encoded pp28 is required for the cytoplasmic envelopment of tegument-associated capsids.

Journal of virology ·Vol. 77 ·No. 19 ·2003-10-00 ·Pages 10594-605

Silva MC, Yu QC, Enquist L, Shenk T

Abstract

The human cytomegalovirus UL99-encoded pp28 is a myristylated phosphoprotein that is a constituent of the virion. The pp28 protein is positioned within the tegument of the virus particle, a protein structure that resides between the capsid and envelope. In the infected cell, pp28 is found in a cytoplasmic compartment derived from the Golgi apparatus, where the virus buds into vesicles to acquire its final membrane. We have constructed two mutants of human cytomegalovirus that fail to produce the pp28 protein, a substitution mutant (BADsubUL99) and a point mutant (BADpmUL99), and we have propagated them by complementation in pp28-expressing fibroblasts. Both mutant viruses are profoundly defective for growth in normal fibroblasts; no infectious virus could be detected after infection. Whereas normal levels of viral DNA and late proteins were observed in mutant virus-infected cells, large numbers of tegument-associated capsids accumulated in the cytoplasm that failed to acquire an envelope. We conclude that pp28 is required for the final envelopment of the human cytomegalovirus virion in the cytoplasm.

MeSH Terms
Capsid/physiology Cells, Cultured Cytomegalovirus/physiology Cytoplasm/virology Humans Phosphoproteins/genetics,metabolism,physiology Viral Envelope Proteins/metabolism Viral Matrix Proteins/metabolism Viral Proteins/genetics,physiology Virus Assembly Virus Replication
Chemicals
Phosphoproteins Viral Envelope Proteins Viral Matrix Proteins Viral Proteins cytomegalovirus matrix protein 65kDa glycoprotein B, Simplexvirus human cytomegalovirus protein pp28
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Silva Maria C
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544-1014, USA.
Yu Qian-Chun
Enquist Lynn
Shenk Thomas
References (60)
60 references, click to expand
  1. Inhibition of human cytomegalovirus maturation by brefeldin A.
    J Gen Virol. 1992 Oct;73 ( Pt 10):2679-92 PMID: 1328480
  2. Herpes simplex virus and human cytomegalovirus replication in WI-38 cells. I. Sequence of viral replication.
    J Virol. 1973 Oct;12(4):919-30 PMID: 4359959
  3. A herpes simplex virus 1 US11-expressing cell line is resistant to herpes simplex virus infection at a step in viral entry mediated by glycoprotein D.
    J Virol. 1994 May;68(5):2830-9 PMID: 8151754
  4. The phospholipid composition of extracellular herpes simplex virions differs from that of host cell nuclei.
    Virology. 1994 May 1;200(2):831-6 PMID: 8178468
  5. Cloning, characterization, and expression of the murine cytomegalovirus homologue of the human cytomegalovirus 28-kDa matrix phosphoprotein (UL99).
    Virology. 1994 Dec;205(2):417-29 PMID: 7975245
  6. Electrophoretic analysis of polypeptides immune precipitated from cytomegalovirus-infected cell extracts by human sera.
    Infect Immun. 1982 Jun;36(3):933-42 PMID: 6284646
  7. Characterization of monoclonal antibodies and polyclonal immune sera directed against human cytomegalovirus virion proteins.
    Virology. 1984 Jan 30;132(2):325-38 PMID: 6322416
  8. Human immune response to cytomegalovirus structural polypeptides studied by immunoblotting.
    J Med Virol. 1985 Dec;17(4):303-11 PMID: 3001220
  9. Myristylation site in Pr65gag is essential for virus particle formation by Moloney murine leukemia virus.
    Proc Natl Acad Sci U S A. 1986 Oct;83(19):7246-50 PMID: 3489936
  10. Molecular cloning and analysis of three cDNA clones homologous to human cytomegalovirus RNAs present during late infection.
    J Virol. 1986 Nov;60(2):531-8 PMID: 3021986
  11. Human cytomegalovirus structural components: intracellular and intraviral localization of p28 and p65-69 by immunoelectron microscopy.
    Virus Res. 1987 Jul;8(1):15-23 PMID: 2821705
  12. Human cytomegalovirus morphogenesis: an ultrastructural study of the late cytoplasmic phases.
    Arch Virol. 1988;98(1-2):51-64 PMID: 2829797
  13. Identification and procaryotic expression of the gene coding for the highly immunogenic 28-kilodalton structural phosphoprotein (pp28) of human cytomegalovirus.
    J Virol. 1988 Jul;62(7):2243-50 PMID: 2836608
  14. Analysis of a region of the human cytomegalovirus (AD169) genome coding for a 25-kilodalton virion protein.
    J Virol. 1989 Jan;63(1):233-41 PMID: 2535729
  15. Gene UL11 of herpes simplex virus type 1 encodes a virion protein which is myristylated.
    J Gen Virol. 1989 Dec;70 ( Pt 12):3147-57 PMID: 2558153
  16. Myristoylation-dependent replication and assembly of human immunodeficiency virus 1.
    Proc Natl Acad Sci U S A. 1990 Jan;87(2):523-7 PMID: 2405382
  17. Analysis of the protein-coding content of the sequence of human cytomegalovirus strain AD169.
    Curr Top Microbiol Immunol. 1990;154:125-69 PMID: 2161319
  18. Effect of brefeldin A on alphaherpesvirus membrane protein glycosylation and virus egress.
    J Virol. 1991 Mar;65(3):1066-81 PMID: 1847436
  19. Brefeldin A arrests the maturation and egress of herpes simplex virus particles during infection.
    J Virol. 1991 Apr;65(4):1893-904 PMID: 1848309
  20. Human cytomegalovirus strain Towne pp28 gene: sequence comparison to pp28 of HCMV AD169 and stable expression in Chinese hamster ovary cells.
    Virology. 1991 Oct;184(2):762-7 PMID: 1653497
  21. The myristylated virion proteins of herpes simplex virus type 1: investigation of their role in the virus life cycle.
    J Gen Virol. 1992 Mar;73 ( Pt 3):539-47 PMID: 1312117
  22. Human cytomegalovirus contains a tegument protein that enhances transcription from promoters with upstream ATF and AP-1 cis-acting elements.
    J Virol. 1992 Jul;66(7):4434-44 PMID: 1318413
  23. The UL11 gene of herpes simplex virus 1 encodes a function that facilitates nucleocapsid envelopment and egress from cells.
    J Virol. 1992 Aug;66(8):5168-74 PMID: 1321297
  24. Analysis and mapping of a family of 3'-coterminal transcripts containing coding sequences for human cytomegalovirus open reading frames UL93 through UL99.
    J Virol. 1995 Mar;69(3):1521-31 PMID: 7853485
  25. Proteins associated with purified human cytomegalovirus particles.
    J Virol. 1996 Sep;70(9):6097-105 PMID: 8709233
  26. Episomal vectors rapidly and stably produce high-titer recombinant retrovirus.
    Hum Gene Ther. 1996 Aug 1;7(12):1405-13 PMID: 8844199
  27. Cytomegalovirus selectively blocks antigen processing and presentation of its immediate-early gene product.
    Nature. 1996 Oct 24;383(6602):720-2 PMID: 8878482
  28. Analysis of the complete DNA sequence of murine cytomegalovirus.
    J Virol. 1996 Dec;70(12):8833-49 PMID: 8971012
  29. Translational regulation of the human cytomegalovirus pp28 (UL99) late gene.
    J Virol. 1997 Feb;71(2):981-7 PMID: 8995616
  30. Intracellular localization and expression of the human cytomegalovirus matrix phosphoprotein pp71 (ppUL82): evidence for its translocation into the nucleus.
    J Gen Virol. 1996 Dec;77 ( Pt 12):3087-97 PMID: 9000101
  31. Nuclear localization of the human cytomegalovirus tegument protein pp150 (ppUL32).
    J Gen Virol. 1995 Jul;76 ( Pt 7):1591-601 PMID: 9049366
  32. Structure and assembly of the virion.
    Intervirology. 1996;39(5-6):389-400 PMID: 9130048
  33. Human cytomegalovirus tegument protein pp71 (ppUL82) enhances the infectivity of viral DNA and accelerates the infectious cycle.
    J Virol. 1997 Jun;71(6):4400-8 PMID: 9151830
  34. Localization of human cytomegalovirus structural proteins to the nuclear matrix of infected human fibroblasts.
    J Virol. 1998 Apr;72(4):3321-9 PMID: 9525659
  35. Infection and spread of alphaherpesviruses in the nervous system.
    Adv Virus Res. 1998;51:237-347 PMID: 9891589
  36. Capsid structure of simian cytomegalovirus from cryoelectron microscopy: evidence for tegument attachment sites.
    J Virol. 1999 Mar;73(3):2181-92 PMID: 9971801
  37. Expression and characterization of a novel structural protein of human cytomegalovirus, pUL25.
    J Virol. 1999 May;73(5):3800-9 PMID: 10196274
  38. DNA microarrays of the complex human cytomegalovirus genome: profiling kinetic class with drug sensitivity of viral gene expression.
    J Virol. 1999 Jul;73(7):5757-66 PMID: 10364327
  39. Construction and transposon mutagenesis in Escherichia coli of a full-length infectious clone of pseudorabies virus, an alphaherpesvirus.
    J Virol. 1999 Aug;73(8):6405-14 PMID: 10400733
  40. Three-dimensional visualization of tegument/capsid interactions in the intact human cytomegalovirus.
    Virology. 1999 Jul 20;260(1):10-6 PMID: 10405351
  41. The herpes simplex virus 1 UL11 proteins are associated with cytoplasmic and nuclear membranes and with nuclear bodies of infected cells.
    J Virol. 1995 Feb;69(2):825-33 PMID: 7815549
  42. Accumulation of virion tegument and envelope proteins in a stable cytoplasmic compartment during human cytomegalovirus replication: characterization of a potential site of virus assembly.
    J Virol. 2000 Jan;74(2):975-86 PMID: 10623760
  43. ERGIC-53 and traffic in the secretory pathway.
    J Cell Sci. 2000 Feb;113 ( Pt 4):587-96 PMID: 10652252
  44. Human cytomegalovirus UL69 protein is required for efficient accumulation of infected cells in the G1 phase of the cell cycle.
    Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2692-6 PMID: 10706637
  45. Human cytomegalovirus pp28 (UL99) localizes to a cytoplasmic compartment which overlaps the endoplasmic reticulum-golgi-intermediate compartment.
    J Virol. 2000 Apr;74(8):3842-51 PMID: 10729158
  46. A self-recombining bacterial artificial chromosome and its application for analysis of herpesvirus pathogenesis.
    Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4873-8 PMID: 10781094
  47. Membrane targeting properties of a herpesvirus tegument protein-retrovirus Gag chimera.
    J Virol. 2000 Sep;74(18):8692-9 PMID: 10954570
  48. UL82 virion protein activates expression of immediate early viral genes in human cytomegalovirus-infected cells.
    Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14506-11 PMID: 11121054
  49. Herpes simplex virus nucleocapsids mature to progeny virions by an envelopment --> deenvelopment --> reenvelopment pathway.
    J Virol. 2001 Jun;75(12):5697-702 PMID: 11356979
  50. Cytomegalovirus basic phosphoprotein (pUL32) binds to capsids in vitro through its amino one-third.
    J Virol. 2001 Aug;75(15):6865-73 PMID: 11435566
  51. Intracellular trafficking of the UL11 tegument protein of herpes simplex virus type 1.
    J Virol. 2001 Dec;75(24):12209-19 PMID: 11711612
  52. Human cytomegalovirus UL47 tegument protein functions after entry and before immediate-early gene expression.
    J Virol. 2002 Feb;76(3):1043-50 PMID: 11773380
  53. Herpesvirus assembly and egress.
    J Virol. 2002 Feb;76(4):1537-47 PMID: 11799148
  54. Construction of a self-excisable bacterial artificial chromosome containing the human cytomegalovirus genome and mutagenesis of the diploid TRL/IRL13 gene.
    J Virol. 2002 Mar;76(5):2316-28 PMID: 11836410
  55. The products of human cytomegalovirus genes UL23, UL24, UL43 and US22 are tegument components.
    J Gen Virol. 2002 Jun;83(Pt 6):1315-24 PMID: 12029146
  56. 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. 2002 Sep;76(17):8939-52 PMID: 12163613
  57. The human cytomegalovirus genome revisited: comparison with the chimpanzee cytomegalovirus genome.
    J Gen Virol. 2003 Jan;84(Pt 1):17-28 PMID: 12533697
  58. Envelopment of human cytomegalovirus occurs by budding into Golgi-derived vacuole compartments positive for gB, Rab 3, trans-golgi network 46, and mannosidase II.
    J Virol. 2003 Mar;77(5):3191-203 PMID: 12584343
  59. Human cytomegalovirus pp71 stimulates cell cycle progression by inducing the proteasome-dependent degradation of the retinoblastoma family of tumor suppressors.
    Mol Cell Biol. 2003 Mar;23(6):1885-95 PMID: 12612064
  60. Progeny vaccinia and human cytomegalovirus particles utilize early endosomal cisternae for their envelopes.
    Eur J Cell Biol. 1993 Feb;60(1):163-78 PMID: 8385018
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
Published
2003-10-00
Pages
10594-605
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC228509
Subset
IM
Grants
NCI NIH HHS · R01 CA082396 · United States
NCI NIH HHS · CA82396 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com