Abstract
Genital herpes is an intractable disease caused mainly by herpes simplex virus (HSV) type 2 (HSV-2), and is a major concern in public health. A previous infection with HSV type 1 (HSV-1) enhances protection against primary HSV-2 infection to some extent. In this study, we evaluated the ability of HF10, a naturally occurring replication-competent HSV-1 mutant, to protect against genital infection in mice caused by HSV-2. Subcutaneous inoculation of HF10-immunized mice against lethal infection by HSV-2, and attenuated the development of genital ulcer diseases. Immunization with HF10 inhibited HSV-2 replication in the mouse vagina, reduced local inflammation, controlled emergence of neurological dysfunctions of HSV-2 infection, and increased survival. In HF10-immunized mice, we observed rapid and increased production of interferon-γ in the vagina in response to HSV-2 infection, and numerous CD4+ and a few CD8+ T cells localized to the infective focus. CD4+ T cells invaded the mucosal subepithelial lamina propria. Thus, the protective effect of HF10 was related to induction of cellular immunity, mediated primarily by Th1 CD4+ cells. These data indicate that the live attenuated HSV-1 mutant strain HF10 is a promising candidate antigen for a vaccine against genital herpes caused by HSV-2.
Highlights
Herpes simplex virus (HSV) type 1 (HSV-1) and type 2 (HSV2) belong to the alphaherpesvirus family
In HF10-immunized mice, HSV-2 antigen staining was restricted to the mucosal surface at days 1 and 4 and was undetectable 6 days after challenge. These results indicate that mice immunized with HF10 were protected against severe genital disease caused by HSV-2
Immunization with HSV type 1 (HSV-1) may be useful for preventing infection with or disease caused by HSV-2
Summary
Herpes simplex virus (HSV) type 1 (HSV-1) and type 2 (HSV2) belong to the alphaherpesvirus family. HSV1 infects via the oral route, whereas HSV-2 infects via the genital tract. Both exert neurotropic effects and spread to the nervous system (Corey and Spear, 1986; Whitley and Roizman, 2001). Epidemiological investigations have indicated that the prevalence of HSV-2 in the general population of the USA ranges from 10 to 60%, and genital herpes is one of the most common sexually transmitted diseases (Malvy et al, 2005; Xu et al, 2006). HSV1 has become a major causative agent of primary genital herpes in developed countries (Lafferty et al, 2000; Nieuwenhuis et al, 2006)
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