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Journal of Virology, January 2008, p. 795-804, Vol. 82, No. 2
0022-538X/08/$08.00+0     doi:10.1128/JVI.01722-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Varicella-Zoster Virus Glycoprotein M Homolog Is Glycosylated, Is Expressed on the Viral Envelope, and Functions in Virus Cell-to-Cell Spread{triangledown}

Yoshiaki Yamagishi,1,2,{dagger} Tomohiko Sadaoka,1,{dagger} Hironori Yoshii,1,3 Pranee Somboonthum,1 Takayoshi Imazawa,4 Kazuhiro Nagaike,3 Keiichi Ozono,2 Koichi Yamanishi,1 and Yasuko Mori1*

Laboratory of Virology and Vaccinology,1 Laboratory of Toxicogenomics, Division of Biomedical Research, National Institute of Biomedical Innovation, 7-6-8, Saito-Asagi, Ibaraki, Osaka 567-0085,4 Department of Pediatrics, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871,2 Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kannonji, Kagawa, Japan3

Received 7 August 2007/ Accepted 16 October 2007

Although envelope glycoprotein M (gM) is highly conserved among herpesviruses, the varicella-zoster virus (VZV) gM homolog has never been investigated. Here we characterized the VZV gM homolog and analyzed its function in VZV-infected cells. The VZV gM homolog was expressed on virions as a glycoprotein modified with a complex N-linked oligosaccharide and localized mainly to the Golgi apparatus and the trans-Golgi network in infected cells. To analyze its function, a gM deletion mutant was generated using the bacterial artificial chromosome system in Escherichia coli, and the virus was reconstituted in MRC-5 cells. VZV is highly cell associated, and infection proceeds mostly by cell-to-cell spread. Compared with wild-type VZV, the gM deletion mutant showed a 90% reduction in plaque size and 50% of the cell-to-cell spread in MRC-5 cells. The analysis of infected cells by electron microscopy revealed numerous aberrant vacuoles containing electron-dense materials in cells infected with the deletion mutant virus but not in those infected with wild-type virus. However, enveloped immature particles termed L particles were found at the same level on the surfaces of cells infected with either type of virus, indicating that envelopment without a capsid might not be impaired. These results showed that VZV gM is important for efficient cell-to-cell virus spread in cell culture, although it is not essential for virus growth.

* Corresponding author. Mailing address: Laboratory of Virology and Vaccinology, Division of Biomedical Research, National Institute of Biomedical Innovation, 7-6-8, Saito-Asagi, Ibaraki, Osaka 567-0085, Japan. Phone: (81) 72 641 9012. Fax: (81) 72 641 9812. E-mail: ymori{at}nibio.go.jp

{triangledown} Published ahead of print on 31 October 2007.

{dagger} Yoshiaki Yamagishi and Tomohiko Sadaoka contributed equally to this work.

Journal of Virology, January 2008, p. 795-804, Vol. 82, No. 2
0022-538X/08/$08.00+0     doi:10.1128/JVI.01722-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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