Identification of the molecular determinants underlying asymptomatic Ebola virus testicular infections and long-term effects on reproductive health

Ebola virus disease (EVD) outbreaks continue to increase in frequency. Recently, we have witnessed the largest EVD outbreak in recorded history in West Africa, and the ongoing outbreak in the Democratic Republic of Congo is now the second largest. Asymptomatic persistent Ebola virus (EBOV) infections in survivors could result in the initiation of new chains of transmission. This raises important public health concerns. Virus has been found in semen from EVD survivors >500 days following recovery and in the absence of clinical symptoms. Further, sexual transmission of EBOV from survivors resulted in new disease transmission events in multiple EVD outbreaks and represents a major public health and containment concern. Clinical trials with antivirals have suggested that drug treatment has no effect on reducing EBOV persistence within the male reproductive tract. Thus, it is imperative to identify how and when EBOV is transmitted to the male reproductive tract in order to identify treatment and care strategies for patients, as well as help guide containment efforts. The aim of this proposal is to characterize EBOV transmission to the testes and spread of the virus through sexual intercourse. Here, we will identify the mechanisms that help the virus enter into the reproductive tract and the interactions between host cells and the virus that allows for persistence in the testes. We will also examine how these factors relate to sexual transmission using a small animal model of infection. Further, we will also assess the long-term reproductive health complications that are encountered by both male and female EVD survivors in West Africa through questionnaires and analysis of historical samples. This investigation will address critical knowledge gaps in our understanding of this public health concern and will have important impacts for future outbreaks, including informing patient care strategies, outbreak containment and the long-term health of disease survivors.