Guinea Pig Model for Lassa Virus Infection of Reproductive Tract and Considerations for Sexual and Vertical Transmission.

Abstract

Lassa virus (LASV) causes Lassa fever; mortality rates are higher in pregnant women, and fetal infection and death are possible. Sexual transmission after recovery from Lassa fever has occurred. Using virus strains that are lethal (Josiah) or nonlethal (NJ2015) in guinea pigs, we characterized LASV-associated pathology and reproductive tissue tropism in male and female animals. Uterus, ovary, and epididymis were the earliest and most affected tissues; perivascular lymphocytic inflammation was prominent at lethal timepoints and persisted in survivors after clinical disease. LASV-Josiah RNA was detected in reproductive tissues by 4 days postinfection (dpi). Virus localized by immunohistochemistry and in situ hybridization predominantly within vascular smooth muscle and interstitial mesenchymal cells and was widespread in reproductive tissues in lethal infections (12-25 dpi) but not detected in survivors (41-42 dpi). Using a physiologically relevant model, we describe reproductive tissue targets to further elucidate LASV infection and effects on reproductive health and virus transmission.