1887

Abstract

The human cytomegalovirus (HCMV) genes UL128, UL130 and UL131A are essential for endothelial cell infection. Complementation of the defective UL131A gene of the non-endotheliotropic HCMV strain AD169 with wild-type UL131A in an ectopic position restored endothelial cell tropism. The UL131A protein was found in virions in a complex with gH. Coinfection of fibroblasts with UL131A-negative and -positive viruses restored the endothelial cell tropism of UL131A-negative virions by complementing the virions with UL131A protein. Virus entry into endothelial cells, but not into fibroblasts, was blocked by an antipeptide antiserum to pUL131A. AD169, -complemented with wild-type UL131A, showed an impaired release of infectious particles from fibroblasts. A comparable defect in virus release was observed when UL131A was expressed ectopically in a virus background already expressing an intact copy of UL131A. In contrast, virus release from infected endothelial cells was not affected by UL131A. These data suggest a dual role for pUL131A in virus entry and virus exit from infected cells.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.81921-0
2006-09-01
2020-10-22
Loading full text...

Full text loading...

/deliver/fulltext/jgv/87/9/2451.html?itemId=/content/journal/jgv/10.1099/vir.0.81921-0&mimeType=html&fmt=ahah

References

  1. Akter P., Cunningham C., McSharry B. P. & 8 other authors 2003; Two novel spliced genes in human cytomegalovirus. J Gen Virol 84:1117–1122 [CrossRef]
    [Google Scholar]
  2. Bodaghi B., Slobbe-van Drunen M. E. P., Topilko A. & 8 other authors 1999; Entry of human cytomegalovirus into retinal pigment epithelial and endothelial cells by endocytosis. Invest Ophthalmol Vis Sci 40:2598–2607
    [Google Scholar]
  3. Borst E.-M., Hahn G., Koszinowski U. H., Messerle M. 1999; Cloning of the human cytomegalovirus (HCMV) genome as an infectious bacterial artificial chromosome in Escherichia coli : a new approach for construction of HCMV mutants. J Virol 73:8320–8329
    [Google Scholar]
  4. Borza C. M., Hutt-Fletcher L. M. 2002; Alternate replication in B cells and epithelial cells switches tropism of Epstein–Barr virus. Nat Med 8:594–599 [CrossRef]
    [Google Scholar]
  5. Borza C. M., Morgan A. J., Turk S. M., Hutt-Fletcher L. M. 2004; Use of gHgL for attachment of Epstein-Barr virus to epithelial cells compromises infection. J Virol 78:5007–5014 [CrossRef]
    [Google Scholar]
  6. Bubeck A., Wagner M., Ruzsics Z., Lötzerich M., Iglesias M., Singh I. R., Koszinowski U. H. 2004; Comprehensive mutational analysis of a herpesvirus gene in the viral genome context reveals a region essential for virus replication. J Virol 78:8026–8035 [CrossRef]
    [Google Scholar]
  7. Bubić I., Wagner M., Krmpotić A., Saulig T., Kim S., Yokoyama W. M., Jonjić S., Koszinowski U. H. 2004; Gain of virulence caused by loss of a gene in murine cytomegalovirus. J Virol 78:7536–7544 [CrossRef]
    [Google Scholar]
  8. Cherepanov P. P., Wackernagel W. 1995; Gene disruption in Escherichia coli : TcR and KmR cassettes with the option of Flp-catalyzed excision of the antibiotic-resistance determinant. Gene 158:9–14 [CrossRef]
    [Google Scholar]
  9. Compton T., Nepomuceno R. R., Nowlin D. M. 1992; Human cytomegalovirus penetrates host cells by pH-independent fusion at the cell surface. Virology 191:387–395 [CrossRef]
    [Google Scholar]
  10. Gerna G., Percivalle E., Sarasini A., Revello M. G. 2002; Human cytomegalovirus and human umbilical vein endothelial cells: restriction of primary isolation to blood samples and susceptibilities of clinical isolates from other sources to adaptation. J Clin Microbiol 40:233–238 [CrossRef]
    [Google Scholar]
  11. Gerna G., Percivalle E., Lilleri D., Lozza L., Fornara C., Hahn G., Baldanti F., Revello M. G. 2005; Dendritic-cell infection by human cytomegalovirus is restricted to strains carrying functional UL131–128 genes and mediates efficient viral antigen presentation to CD8+ T cells. J Gen Virol 86:275–284 [CrossRef]
    [Google Scholar]
  12. Grazia Revello M., Baldanti F., Percivalle E., Sarasini A., De-Giuli L., Genini E., Lilleri D., Labò N., Gerna G. 2001; In vitro selection of human cytomegalovirus variants unable to transfer virus and virus products from infected cells to polymorphonuclear leukocytes and to grow in endothelial cells. J Gen Virol 82:1429–1438
    [Google Scholar]
  13. Hahn G., Khan H., Baldanti F., Koszinowski U. H., Grazia Revello M., Gerna G. 2002; The human cytomegalovirus ribonucleotide reductase homolog UL45 is dispensable for growth in endothelial cells, as determined by a BAC-cloned clinical isolate of human cytomegalovirus with preserved wild-type characteristics. J Virol 76:9551–9555 [CrossRef]
    [Google Scholar]
  14. Hahn G., Grazia Revello M., Patrone M. & 9 other authors 2004; Human cytomegalovirus UL131-128 genes are indispensable for virus growth in endothelial cells and virus transfer to leukocytes. J Virol 78:10023–10033 [CrossRef]
    [Google Scholar]
  15. Hirt B. 1967; Selective extraction of polyoma DNA from infected mouse cell cultures. J Mol Biol 26:365–369 [CrossRef]
    [Google Scholar]
  16. Kahl M., Siegel-Axel D., Stenglein S., Jahn G., Sinzger C. 2000; Efficient lytic infection of human arterial endothelial cells by human cytomegalovirus strains. J Virol 74:7628–7635 [CrossRef]
    [Google Scholar]
  17. MacCormac L. P., Grundy J. E. 1999; Two clinical isolates and the Toledo strain of cytomegalovirus contain endothelial cell tropic variants that are not present in the AD169, Towne, or Davis strains. J Med Virol 57:298–307 [CrossRef]
    [Google Scholar]
  18. Messerle M., Crnkovic I., Hammerschmidt W., Ziegler H., Koszinowski U. H. 1997; Cloning and mutagenesis of a herpesvirus genome as an infectious bacterial artificial chromosome. Proc Natl Acad Sci U S A 94:14759–14763 [CrossRef]
    [Google Scholar]
  19. Mori Y., Akkapaiboon P., Yang X., Yamanishi K. 2003; The human herpesvirus 6 U100 gene product is the third component of the gH-gL glycoprotein complex on the viral envelope. J Virol 77:2452–2458 [CrossRef]
    [Google Scholar]
  20. Mori Y., Akkapaiboon P., Yonemoto S. & 7 other authors 2004; Discovery of a second form of tripartite complex containing gH-gL of human herpesvirus 6 and observations on CD46. J Virol 78:4609–4616 [CrossRef]
    [Google Scholar]
  21. Pass R. F. 2001; Cytomegalovirus. In Fields Virology , 4th edn. pp  2675–2705 Edited by Knipe D. M., Howley P. M., Griffin D. E., Martin M. A., Lamb R. A., Roizman B., Straus S. E. Philadelphia, PA: Lippincott Williams & Wilkins;
    [Google Scholar]
  22. Patrone M., Secchi M., Fiorina L., Ierardi M., Milanesi G., Gallina A. 2005; Human cytomegalovirus UL130 protein promotes endothelial cell infection through a producer cell modification of the virion. J Virol 79:8361–8373 [CrossRef]
    [Google Scholar]
  23. Plachter B., Sinzger C., Jahn G. 1996; Cell types involved in replication and distribution of human cytomegalovirus. Adv Virus Res 46:195–261
    [Google Scholar]
  24. Rupp B., Ruzsics Z., Sacher T., Koszinowski U. H. 2005; Conditional cytomegalovirus replication in vitro and in vivo. J Virol 79:486–494 [CrossRef]
    [Google Scholar]
  25. Ryckman B. J., Jarvis M. A., Drummond D. D., Nelson J. A., Johnson D. C. 2006; Human cytomegalovirus entry into epithelial and endothelial cells depends on genes UL128 to UL150 and occurs by endocytosis and low-pH fusion. J Virol 80:710–722 [CrossRef]
    [Google Scholar]
  26. Sanchez V., Greis K. D., Sztul E., Britt W. J. 2000; 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 74:975–986 [CrossRef]
    [Google Scholar]
  27. Sinzger C., Schmidt K., Knapp J., Kahl M., Beck R., Waldman J., Hebart H., Einsele H., Jahn G. 1999; Modification of human cytomegalovirus tropism through propagation in vitro is associated with changes in the viral genome. J Gen Virol 80:2867–2877
    [Google Scholar]
  28. Sinzger C., Kahl M., Laib K., Klingel K., Rieger P., Plachter B., Jahn G. 2000; Tropism of human cytomegalovirus for endothelial cells is determined by a post-entry step dependent on efficient translocation to the nucleus. J Gen Virol 81:3021–3035
    [Google Scholar]
  29. Spear P. G., Longnecker R. 2003; Herpesvirus entry: an update. J Virol 77:10179–10185 [CrossRef]
    [Google Scholar]
  30. Venetsanakos E., Mirza A., Fanton C., Romanov S. R., Tlsty T., McMahon M. 2002; Induction of tubulogenesis in telomerase-immortalized human microvascular endothelial cells by glioblastoma cells. Exp Cell Res 273:21–33 [CrossRef]
    [Google Scholar]
  31. Wagner M., Gutermann A., Podlech J., Reddehase M. J., Koszinowski U. H. 2002; Major histocompatibility complex class I allele-specific cooperative and competitive interactions between immune evasion proteins of cytomegalovirus. J Exp Med 196:805–816 [CrossRef]
    [Google Scholar]
  32. Waldman W. J., Sneddon J. M., Stephens R. E., Roberts W. H. 1989; Enhanced endothelial cytopathogenicity induced by a cytomegalovirus strain propagated in endothelial cells. J Med Virol 28:223–230 [CrossRef]
    [Google Scholar]
  33. Wang D., Shenk T. 2005a; Human cytomegalovirus UL131 open reading frame is required for epithelial cell tropism. J Virol 79:10330–10338 [CrossRef]
    [Google Scholar]
  34. Wang D., Shenk T. 2005b; Human cytomegalovirus virion protein complex required for epithelial and endothelial cell tropism. Proc Natl Acad Sci U S A 102:18153–18158 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.81921-0
Loading
/content/journal/jgv/10.1099/vir.0.81921-0
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

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