Female genital tract secretions inhibit herpes simplex virus infection: correlation with soluble mucosal immune mediators and impact of hormonal contraception

Abstract

Problem: Female genital tract secretions inhibit herpes simplex virus (HSV) infection, however, the intra- and inter-subject variability, contribution of specific mediators, and impact of reproductive hormones have not been defined.

Method: of study Cervicovaginal lavage (CVL) (n = 89) obtained from nine cyclers and seven women on hormonal contraception (HC), who completed between three and eight weekly visits, were examined for anti-herpes simplex virus activity and concentrations of mediators.

Results: The CVL inhibited HSV infection by a mean value of approximately 57% during the follicular or luteal phase, but only by 36% in hormonal contraceptive users. Human neutrophil peptides 1-3 (HNP1-3) (P = 0.03), IL-8 (P = 0.003), lactoferrin (P = 0.005), lysozyme (P = 0.003), IgA (P = 0.002), and IgG (P = 0.02) correlated with antiviral activity. Intra-subject and inter-subject variability was observed, suggesting that factors other than hormones contribute to innate defense.

Conclusion: Endogenous antimicrobial activity may provide a biomarker of healthy mucosal immunity and may be reduced in the setting of HC. However, larger prospective studies are needed.

Fig. 1. Reduction in the endogenous anti-HSV activity in CVL obtained from women using hormonal contraception compared to cycling women in the follicular or luteal phase

CaSki cells were infected with HSV-2(G) in the presence of each CVL sample or matched control buffer (PBS containing 200 μg/ml BSA, antibiotics and protease inhibitors) and viral plaques counted 48 hours post-infection. Each point represents the percentage reduction in viral plaque formation relative to cells treated with control buffer obtained from two independent experiments conducted in duplicate. Each color represents a different participant. The bars indicate means ± SD for the group.

Fig. 2. Anti-HSV activity correlates with soluble mucosal immune mediators

The concentrations of HNP1-3, IL-8, lactoferrin, lysozyme, IgA, and IgG were determined and the data log transformed. The percentage inhibition of HSV infection was determined by plaque assay. Each symbol represents the results obtained from a single CVL sample tested in duplicate in two independent experiments. Correlation coefficients were determined by weighted Pearson product-moment correlations (See Table 2)