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

A Functional YNKI Motif in the Short Cytoplasmic Tail of Varicella-Zoster Virus Glycoprotein gH Mediates Clathrin-Dependent and Antibody-Independent Endocytosis

Departments of Microbiology and Pediatrics, University of Iowa, Iowa City, Iowa

Received 30 September 2002/ Accepted 6 January 2003

The trafficking of varicella-zoster virus (VZV) gH was investigated under both infection and transfection conditions. In initial endocytosis assays performed in infected cells, the three glycoproteins gE, gI, and gB served as positive controls for internalization from the plasma membrane. Subsequently, we discovered that gH in VZV-infected cells was also internalized and followed a similar trafficking pattern. This observation was unexpected because all herpesvirus gH homologues have short endodomains not known to contain trafficking motifs. Further investigation demonstrated that VZV gH, when expressed alone with its chaperone gL, was capable of endocytosis in a clathrin-dependent manner, independent of gE, gI, or gB. Upon inspection of the short gH cytoplasmic tail, we discovered a putative tyrosine-based endocytosis motif (YNKI). When the tyrosine was replaced with an alanine, endocytosis of gH was blocked. Utilizing an endocytosis assay dependent on biotin labeling, we further documented that endocytosis of VZV gH was antibody independent. In control experiments, we showed that gE, gI, and gB also internalized in an antibody-independent manner. Alignment analysis of the VZV gH cytoplasmic tail to other herpesvirus gH homologues revealed two important findings: (i) herpes simplex virus type 1 and 2 homologues lacked an endocytosis motif, while all other alphaherpesvirus gH homologues contained a potential motif, and (ii) the VZV gH and simian varicella virus gH cytoplasmic tails were likely longer in length (18 amino acids) than predicted in the original sequence analyses (12 and 16 amino acids, respectively). The longer tails provided the proper context for a functional endocytosis motif.

This article has been cited by other articles:

• Tomlinson, C. C., Damania, B. (2008). Critical Role for Endocytosis in the Regulation of Signaling by the Kaposi's Sarcoma-Associated Herpesvirus K1 Protein. J. Virol. 82: 6514-6523 [Abstract] [Full Text]  
• Beitia Ortiz de Zarate, I., Cantero-Aguilar, L., Longo, M., Berlioz-Torrent, C., Rozenberg, F. (2007). Contribution of Endocytic Motifs in the Cytoplasmic Tail of Herpes Simplex Virus Type 1 Glycoprotein B to Virus Replication and Cell-Cell Fusion. J. Virol. 81: 13889-13903 [Abstract] [Full Text]  
• Turcotte, S., Letellier, J., Lippe, 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 [Abstract] [Full Text]  
• Ficinska, J., Van Minnebruggen, G., Nauwynck, H. J., Bienkowska-Szewczyk, K., Favoreel, H. W. (2005). Pseudorabies Virus Glycoprotein gD Contains a Functional Endocytosis Motif That Acts in Concert with an Endocytosis Motif in gB To Drive Internalization of Antibody-Antigen Complexes from the Surface of Infected Monocytes. J. Virol. 79: 7248-7254 [Abstract] [Full Text]  
• Vogt, C., Eickmann, M., Diederich, S., Moll, M., Maisner, A. (2005). Endocytosis of the Nipah Virus Glycoproteins. J. Virol. 79: 3865-3872 [Abstract] [Full Text]  
• Maresova, L., Pasieka, T. J., Homan, E., Gerday, E., Grose, C. (2005). Incorporation of Three Endocytosed Varicella-Zoster Virus Glycoproteins, gE, gH, and gB, into the Virion Envelope. J. Virol. 79: 997-1007 [Abstract] [Full Text]  
• Van Minnebruggen, G., Favoreel, H. W., Nauwynck, H. J. (2004). Internalization of Pseudorabies Virus Glycoprotein B Is Mediated by an Interaction between the YQRL Motif in Its Cytoplasmic Domain and the Clathrin-Associated AP-2 Adaptor Complex. J. Virol. 78: 8852-8859 [Abstract] [Full Text]  
• Avitabile, E., Lombardi, G., Gianni, T., Capri, M., Campadelli-Fiume, G. (2004). Coexpression of UL20p and gK Inhibits Cell-Cell Fusion Mediated by Herpes Simplex Virus Glycoproteins gD, gH-gL, and Wild-Type gB or an Endocytosis-Defective gB Mutant and Downmodulates Their Cell Surface Expression. J. Virol. 78: 8015-8025 [Abstract] [Full Text]  
• Sprague, E. R., Martin, W. L., Bjorkman, P. J. (2004). pH Dependence and Stoichiometry of Binding to the Fc Region of IgG by the Herpes Simplex Virus Fc Receptor gE-gI. J. Biol. Chem. 279: 14184-14193 [Abstract] [Full Text]  
• Pasieka, T. J., Maresova, L., Shiraki, K., Grose, C. (2004). Regulation of Varicella-Zoster Virus-Induced Cell-to-Cell Fusion by the Endocytosis-Competent Glycoproteins gH and gE. J. Virol. 78: 2884-2896 [Abstract] [Full Text]  
• Beitia Ortiz de Zarate, I., Kaelin, K., Rozenberg, F. (2004). Effects of Mutations in the Cytoplasmic Domain of Herpes Simplex Virus Type 1 Glycoprotein B on Intracellular Transport and Infectivity. J. Virol. 78: 1540-1551 [Abstract] [Full Text]