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Journal of Virology, October 2006, p. 9481-9496, Vol. 80, No. 19
0022-538X/06/$08.00+0     doi:10.1128/JVI.00533-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Essential Functions of the Unique N-Terminal Region of the Varicella-Zoster Virus Glycoprotein E Ectodomain in Viral Replication and in the Pathogenesis of Skin Infection

Barbara Berarducci,1* Minako Ikoma,2 Shaye Stamatis,1 Marvin Sommer,1 Charles Grose,2 and Ann M. Arvin1

Department of Pediatrics and Microbiology and Immunology, Stanford University School of Medicine, Stanford, California,1 Department of Pediatrics and Central Microscopy Research Facility, University of Iowa, Iowa City, Iowa2

Received 14 March 2006/ Accepted 14 July 2006

Varicella-zoster virus (VZV) glycoprotein E (gE) is a multifunctional protein important for cell-cell spread, envelopment, and possibly entry. In contrast to other alphaherpesviruses, gE is essential for VZV replication. Interestingly, the N-terminal region of gE, comprised of amino acids 1 to 188, was shown not to be conserved in the other alphaherpesviruses by bioinformatics analysis. Mutational analysis was performed to investigate the functions associated with this unique gE N-terminal region. Linker insertions, serine-to-alanine mutations, and deletions were introduced in the gE N-terminal region in the VZV genome, and the effects of these mutations on virus replication and cell-cell spread, gE trafficking and localization, virion formation, and replication in vivo in the skin were analyzed. In summary, mutagenesis of the gE N-terminal region identified a new functional region in the VZV gE ectodomain essential for cell-cell spread and the pathogenesis of VZV skin tropism and demonstrated that different subdomains of the unique N-terminal region had specific roles in viral replication, cell-cell spread, and secondary envelopment.

* Corresponding author. Mailing address: Stanford University School of Medicine, 300 Pasteur Dr., Rm G312, Stanford, CA 94305-5208. Phone: (650) 725-6555. Fax: (650) 725-8040. E-mail: bbarbara{at}stanford.edu.

Journal of Virology, October 2006, p. 9481-9496, Vol. 80, No. 19
0022-538X/06/$08.00+0     doi:10.1128/JVI.00533-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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