Date of Award:

5-2019

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Animal, Dairy, and Veterinary Sciences

Advisor/Chair:

Justin Julander

Co-Advisor/Chair:

Arnaud Van Wettere

Third Advisor:

Brian Gowen

Abstract

Zika virus (ZIKV) is a sexually transmitted viral infection most frequently transmitted by mosquitoes. The source of infectious virions in the male reproductive tract has yet to be elucidated. The goals of the studies included developing and characterizing two mouse models for reproductive transmission studies and demonstration of sexual transmission of virus via artificial insemination. The mouse strains used in the study lacked receptors to interferon molecules, key signaling proteins of the host immune response. Inflammation severity was assessed during acute disease, 5-11 days after infection using a novel histopathology grading system. ZIKV proteins and genome were initially detected in epididymal epithelial cells in males. Inflammation was first observed in the epididymis and progressed to the testicle in both AG129 and Ifnar-/- males. Infection of Ifnar-/- mice may better recapitulate Zika virus pathology in humans due to milder histopathologic lesions, the presence of histologically normal sperm in epididymal tubules, and an ability to survive the acute phase of disease. In further studies, male Ifnar-/- mice were challenged subcutaneously with ZIKV. Artificial insemination fluid derived from experimentally infected males showed positive sexual transmission at 7 days post infection (DPI) but not 35 or 70 DPI. These studies show passage of virus from epididymal flush and seminal plasma to females via insemination during acute ZIKV disease in males and provides a model for sexual transmission of ZIKV.

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Available for download on Wednesday, May 01, 2024

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