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Journal of Virology, March 2004, p. 2530-2536, Vol. 78, No. 5
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.5.2530-2536.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

In Vivo Role of Nectin-1 in Entry of Herpes Simplex Virus Type 1 (HSV-1) and HSV-2 through the Vaginal Mucosa

Melissa M. Linehan,1 Susan Richman,2 Claude Krummenacher,3 Roselyn J. Eisenberg,4 Gary H. Cohen,3 and Akiko Iwasaki1,5*

Department of Epidemiology and Public Health,1 Department of Obstetrics and Gynecology,2 Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520,5 Department of Microbiology, School of Dental Medicine,3 Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 191044

Received 30 September 2003/ Accepted 27 October 2003

Herpes simplex virus type 2 (HSV-2) is transmitted through the genital mucosa during sexual encounters. In recent years, HSV-1 has also become commonly associated with primary genital herpes. The mechanism of viral entry of HSV-1 and HSV-2 in the female genital tract is unknown. In order to understand the molecular interactions required for HSV entry into the vaginal epithelium, we examined the expression of herpesvirus entry mediator nectin-1 in the vagina of human and mouse at different stages of their hormonal cycle. Nectin-1 was highly expressed in the epithelium of human vagina throughout the menstrual cycle, whereas the mouse vaginal epithelium expressed nectin-1 only during the stages of the estrous cycle in which mice are susceptible to vaginal HSV infection. Furthermore, the ability of nectin-1 to mediate viral entry following intravaginal inoculation was examined in a mouse model of genital herpes. Vaginal infection with either HSV-1 or HSV-2 was blocked by preincubation of the virus with soluble recombinant nectin-1. Viral entry through the vaginal mucosa was also inhibited by preincubation of HSV-2 with antibody against gD. Together, these results suggest the importance of nectin-1 in mediating viral entry for both HSV-1 and HSV-2 in the genital mucosa in female hosts.

* Corresponding author. Mailing address: Department of Epidemiology and Public Health, 60 College St., LEPH 716, New Haven, CT 06510. Phone: (203) 785-2919. Fax: (203) 785-7552. E-mail: akiko.iwasaki{at}yale.edu.

Journal of Virology, March 2004, p. 2530-2536, Vol. 78, No. 5
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.5.2530-2536.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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