This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ryckman, B. J.
Right arrow Articles by Johnson, D. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ryckman, B. J.
Right arrow Articles by Johnson, D. C.

 Previous Article  |  Next Article 

Journal of Virology, January 2008, p. 60-70, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.01910-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Characterization of the Human Cytomegalovirus gH/gL/UL128-131 Complex That Mediates Entry into Epithelial and Endothelial Cells{triangledown}

Brent J. Ryckman,1* Barb L. Rainish,1 Marie C. Chase,1 Jamie A. Borton,1,2 Jay A. Nelson,1,2 Michael A. Jarvis,1,2 and David C. Johnson1

Department of Molecular Microbiology and Immunology,1 Vaccine and Gene Therapy Institute, Oregon Health and Sciences University, Portland, Oregon 972392

Received 31 August 2007/ Accepted 8 October 2007

The entry of human cytomegalovirus (HCMV) into biologically relevant epithelial and endothelial cells involves endocytosis followed by low-pH-dependent fusion. This entry pathway is facilitated by the HCMV UL128, UL130, and UL131 proteins, which form one or more complexes with the virion envelope glycoprotein gH/gL. gH/gL/UL128-131 complexes appear to be distinct from the gH/gL/gO complex, which likely facilitates entry into fibroblasts. In order to better understand the assembly and protein-protein interactions of gH/gL/UL128-131 complexes, we generated HCMV mutants lacking UL128-131 proteins and nonreplicating adenovirus vectors expressing gH, gL, UL128, UL130, and UL131. Our results demonstrate that UL128, UL130, and UL131 can each independently assemble onto gH/gL scaffolds. However, the binding of individual UL128-131 proteins onto gH/gL can significantly affect the binding of other proteins; for example, UL128 increased the binding of both UL130 and UL131 to gH/gL. Direct interactions between gH/UL130, UL130/UL131, gL/UL128, and UL128/UL130 were also observed. The export of gH/gL complexes from the endoplasmic reticulum (ER) to the Golgi apparatus and cell surface was dramatically increased when all of UL128, UL130, and UL131 were coexpressed with gH/gL (with or without gO expression). Incorporation of gH/gL complexes into the virion envelope requires transport beyond the ER. Thus, we concluded that UL128, UL130, and UL131 must all bind simultaneously onto gH/gL for the production of complexes that can function in entry into epithelial and endothelial cells.

* Corresponding author. Mailing address: 6366 Basic Sciences Building, Mail Code L-220, Department of Molecular Microbiology and Immunology, Oregon Health and Sciences University, 3181 Sam Jackson Park Rd., Portland, OR 97239. Phone: (503) 494-0658. Fax: (503) 494-6862. E-mail: ryckmanb{at}ohsu.edu

{triangledown} Published ahead of print on 17 October 2007.

Journal of Virology, January 2008, p. 60-70, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.01910-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Tandon, R., AuCoin, D. P., Mocarski, E. S. (2009). Human Cytomegalovirus Exploits ESCRT Machinery in the Process of Virion Maturation. J. Virol. 83: 10797-10807 [Abstract] [Full Text]  
  • Miller, M. S., Hertel, L. (2009). Onset of Human Cytomegalovirus Replication in Fibroblasts Requires the Presence of an Intact Vimentin Cytoskeleton. J. Virol. 83: 7015-7028 [Abstract] [Full Text]  
  • Safronetz, D., Hegde, N. R., Ebihara, H., Denton, M., Kobinger, G. P., St. Jeor, S., Feldmann, H., Johnson, D. C. (2009). Adenovirus Vectors Expressing Hantavirus Proteins Protect Hamsters against Lethal Challenge with Andes Virus. J. Virol. 83: 7285-7295 [Abstract] [Full Text]  
  • Lilja, A. E., Shenk, T. (2008). Efficient replication of rhesus cytomegalovirus variants in multiple rhesus and human cell types. Proc. Natl. Acad. Sci. USA 105: 19950-19955 [Abstract] [Full Text]  
  • Vanarsdall, A. L., Ryckman, B. J., Chase, M. C., Johnson, D. C. (2008). Human Cytomegalovirus Glycoproteins gB and gH/gL Mediate Epithelial Cell-Cell Fusion When Expressed either in cis or in trans. J. Virol. 82: 11837-11850 [Abstract] [Full Text]  
  • Schuessler, A., Sampaio, K. L., Sinzger, C. (2008). Charge Cluster-to-Alanine Scanning of UL128 for Fine Tuning of the Endothelial Cell Tropism of Human Cytomegalovirus. J. Virol. 82: 11239-11246 [Abstract] [Full Text]  
  • Ryckman, B. J., Chase, M. C., Johnson, D. C. (2008). HCMV gH/gL/UL128-131 interferes with virus entry into epithelial cells: Evidence for cell type-specific receptors. Proc. Natl. Acad. Sci. USA 105: 14118-14123 [Abstract] [Full Text]  
  • Gerna, G., Sarasini, A., Patrone, M., Percivalle, E., Fiorina, L., Campanini, G., Gallina, A., Baldanti, F., Revello, M. G. (2008). Human cytomegalovirus serum neutralizing antibodies block virus infection of endothelial/epithelial cells, but not fibroblasts, early during primary infection. J. Gen. Virol. 89: 853-865 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»