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Journal of Virology, May 2009, p. 4520-4527, Vol. 83, No. 9
0022-538X/09/$08.00+0     doi:10.1128/JVI.02601-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Entry of Herpes Simplex Virus 1 and Other Alphaherpesviruses via the Paired Immunoglobulin-Like Type 2 Receptor

Jun Arii,^1,3 Masashi Uema,¹ Tomomi Morimoto,¹ Hiroshi Sagara,² Hiroomi Akashi,³ Etsuro Ono,⁴ Hisashi Arase,^5,6 and Yasushi Kawaguchi^1*

Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases,¹ Department of Basic Medical Science, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639,² Department of Veterinary Microbiology, Graduate School of Agricultural and Life Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657,³ Laboratory of Biomedicine, Center of Biomedical Research, Graduate School of Medicine, Kyushu University, Fukuoka 812-8582,⁴ Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871,⁵ WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan⁶

Received 16 December 2008/ Accepted 11 February 2009

Herpes simplex virus 1 (HSV-1) enters cells either via fusion of the virion envelope and host cell plasma membrane or via endocytosis, depending on the cell type. In the study reported here, we investigated a viral entry pathway dependent on the paired immunoglobulin-like type 2 receptor (PILR), a recently identified entry coreceptor for HSV-1 that associates with viral envelope glycoprotein B (gB). Experiments using inhibitors of endocytic pathways and ultrastructural analyses of Chinese hamster ovary (CHO) cells transduced with PILR showed that HSV-1 entry into these cells was via virus-cell fusion at the cell surface. Together with earlier observations that HSV-1 uptake into normal CHO cells and those transduced with a receptor for HSV-1 envelope gD is mediated by endocytosis, these results indicated that expression of PILR produced an alternative HSV-1 entry pathway in CHO cells. We also showed that human and murine PILR were able to mediate entry of pseudorabies virus, a porcine alphaherpesvirus, but not of HSV-2. These results indicated that viral entry via PILR appears to be conserved but that there is a PILR preference among alphaherpesviruses.

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* Corresponding author. Mailing address: Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Phone: 81-3-6409-2070. Fax: 81-3-6409-2072. E-mail: ykawagu{at}ims.u-tokyo.ac.jp

Published ahead of print on 25 February 2009.

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Journal of Virology, May 2009, p. 4520-4527, Vol. 83, No. 9
0022-538X/09/$08.00+0     doi:10.1128/JVI.02601-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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