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02604 IMPACT OF CERVICOVAGINAL SECRETIONS ON HERPES SIMPLEX VIRUS (HSV) INFECTION John, Minnie1 Cervicovaginal secretions have intrinsic antimicrobial activity, which may be important in protecting women against sexually transmitted infections (STI). Defining these innate factors and identifying how they protect against infection is essential for microbicide development because candidate topicals must not interfere with the innate protective activity and these factors could be exploited to facilitate the development of novel microbicides. The anti-HSV activity of cervicovaginal secretions is unknown. Objective: To evaluate the impact of cervicovaginal lavage (CVL) on HSV infection and explore the mechanism(s) of anti-viral activity. Results: CVL was obtained from 20 women (10 age 18-25 and 10 age 26-45) on two occasions 14 days apart and evaluated for anti-HSV activity. We found that CVL (pH ~ 5.0) inhibits HSV infection in all subjects. There was a geometric mean reduction of > 10-fold in HSV-2 recovered in cervical cells cultured in the presence of CVL compared to cells cultured in the presence of control buffer (saline, pH 5.0 + 0.2mg/ml BSA) (p < 0.0001). There was no significant difference in anti-HSV activity in samples obtained on Day 0 compared to Day 14 and between the two age groups. The CVL is active against clinical isolates of HSV-2 and using immortalized human endocervical cells. CVL appears to inhibit viral entry post-binding as evidenced by its ability to prevent nuclear transport of the viral tegument protein VP16, but not to block HSV-2 binding to cells. The anti-HSV activity is retained if cervical cells are pre-treated with CVL, washed, and then inoculated with HSV-2. In contrast, the activity is diminished if virus is first pre-treated with CVL, and diluted prior to inoculating cells. Conclusions: CVL has intrinsic anti-HSV activity, independent of pH, and may interact with the cell surface preventing subsequent viral entry. Candidate components for this anti-viral activity include defensins, SLPI, lactoferrin or mucins Pediatric Infectious Disease Fellow, Minnie John, MD |
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