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Journal of Virology, May 2001, p. 4734-4743, Vol. 75, No. 10
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.10.4734-4743.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Requirement of Interaction of Nectin-1/HveC with Afadin for Efficient Cell-Cell Spread of Herpes Simplex Virus Type 1

Toshiaki Sakisaka,^1,2, Tomokuni Taniguchi,³ Hiroyuki Nakanishi,^1,2 Kenichi Takahashi,^2, Masako Miyahara,² Wataru Ikeda,¹ Shigekazu Yokoyama,¹ Ying-Feng Peng,¹ Koichi Yamanishi,³ and Yoshimi Takai^1,2,*

Department of Molecular Biology and Biochemistry¹ and Department of Microbiology,³ Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, and The Takai Biotimer Project,^§ ERATO, Japan Science and Technology Corporation, c/o JCR Pharmaceuticals Co., Ltd., Nishi-ku, Kobe 651-2241,² Japan

Received 14 August 2000/Accepted 23 February 2001

We recently found a novel cell-cell adhesion system at cadherin-based adherens junctions (AJs), consisting at least of nectin, a Ca²⁺-independent homophilic immunoglobulin-like adhesion molecule, and afadin, an actin filament-binding protein that connects nectin to the actin cytoskeleton. Nectin is associated with cadherin through afadin and -catenin. The cadherin-catenin system increases the concentration of nectin at AJs in an afadin-dependent manner. Nectin constitutes a family consisting of three members: nectin-1, -2, and -3. Nectin-1 serves as an entry and cell-cell spread mediator of herpes simplex virus type 1 (HSV-1). We studied here a role of the interaction of nectin-1 with afadin in entry and/or cell-cell spread of HSV-1. By the use of cadherin-deficient L cells overexpressing the full length of nectin-1 capable of interacting with afadin and L cells overexpressing a truncated form of nectin-1 incapable of interacting with afadin, we found that the interaction of nectin-1 with afadin increased the efficiency of cell-cell spread, but not entry, of HSV-1. This interaction did not affect the binding to nectin-1 of glycoprotein D, a viral component mediating entry of HSV-1 into host cells. Furthermore, the cadherin-catenin system increased the efficiency of cell-cell spread of HSV-1, although it also increased the efficiency of entry of HSV-1. It is likely that efficient cell-cell spread of HSV-1 is caused by afadin-dependent concentrated localization of nectin-1 at cadherin-based AJs.

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^* Corresponding author. Mailing address: Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Japan. Phone: 81-6-6879-3410. Fax: 81-6-6879-3419. E-mail: ytakai{at}molbio.med.osaka-u.ac.jp.

Present address: Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037.

Present address: JCR Pharmaceuticals Co., Ltd., Nishi-ku, Kobe 651-2241, Japan.

^§ The Takai Biotimer Project was closed in September 1999.

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Journal of Virology, May 2001, p. 4734-4743, Vol. 75, No. 10
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.10.4734-4743.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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