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Defining and preserving the innate antiviral activity found in cervicovaginal secretions is critical. Cervicovaginal lavage (CVL) samples were obtained from 20 healthy women and evaluated for anti-herpes simplex virus (HSV) activity. CVL samples reduced HSV-2 yields by 23-fold (median), and the anti-HSV activity of CVL samples correlated with the concentration of human neutrophil peptides (HNP)-1-3. Both CVL samples and HNP-1-3 interacted with virus and prevented entry after binding. Substantially less protective activity was observed in CVL samples obtained from 20 human immunodeficiency virus--infected subjects, but the addition of CVL samples from healthy subjects enhanced the antiviral activity. The significance of the innate activity was further demonstrated by showing that CVL samples prevented murine genital herpes. Fourteen of 15 mice were protected from genital herpes if they were challenged with HSV-2 pretreated with CVL samples from healthy subjects. In contrast, all 15 mice challenged with untreated HSV-2 died. These findings are evidence that cervicovaginal secretions contribute to innate resistance to HSV-2 and identify defensins as contributors to this activity.

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The effects of the carrageenans 1T1 (λ-type), 1C1 (κ/ι-type) and 1C3 (ιι/ν-type), isolated from the red seaweed Gigartina skottsbergii, on herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infection of murine astrocytes were investigated. The three compounds were effective inhibitors of virus replication, as determined by a virus yield inhibition assay, in astrocytes as well as in Vero cells. The 50% inhibitory concentration was in the range of 0.9–3.6 and 0.4–3.2 μg/ml for astrocytes and Vero cells, respectively, whereas the 90% inhibitory concentration ranged from 6.5 to 17.0 μg/ml in astrocytes and from 3.5 to 22.2 μg/ml in Vero cells. No cytotoxicity was detected at concentrations of up to 1,000 μg/ml, indicating high selectivity indices for these compounds. Inhibition of viral cytopathology and antigen expression was also detected in the presence of the carrageenans. The increase in the expression of glial fibrillary acidic protein (GFAP), an activated astrocyte marker, produced during the course of HSV-1 infection in astrocytes, was reversed in the presence of 1C1 and 1C3. By contrast, the λ-carrageenan 1T1 increased the expression of GFAP, independently of HSV-1 infection.

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