The major conclusion from our study is that vaginal infection of mice with a strain of HSV-2 expressing a mutant form of gD unable to engage HVEM leads to a transient increase in mucosal chemokine (CXCL9, CXCL10, and CCL4) and IL-6 levels when compared to infection with HSV-2 expressing wild-type gD. Here, CXCL10 is linked to infection.