# NIH grant: Modeling Ebola virus Persistence and Recrudescence in the Male Reproductive Tract in Collaborative Cross Mice (1UH2AI196622-01) — retained record

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NIH grant 1UH2AI196622-01: Modeling Ebola virus Persistence and Recrudescence in the Male Reproductive Tract in Collaborative Cross Mice
Institute: {'code': 'AI', 'abbreviation': 'NIAID', 'name': 'National Institute of Allergy and Infectious Diseases', 'admin_org_id': '12500003', 'admin_funding_url': ''}. PI: Alexandra  Schaefer. Award: $233250.
Start: 2026-09-24T00:00:00.
ABSTRACT
The goal of these studies is to define and characterize the establishment of Ebola virus (EBOV) persistence
and reactivation after recovery from acute infection. Based upon existing data, EBOV invades immune
privileged sites, including the eyes, brain, and male and female reproductive tracts. Moreover, EBOV persists
for extended period of times in the male reproductive tract and live virus is detected in semen of male EVD
survivors. Importantly, it is hypothesized that reactivation of persisting virus in the male reproductive tract may
be the source for EBOV reemergence. Experiments to study EBOV persistence in non-human primates (NHPs),
have been hampered by the severity of disease and high lethality during acute infection. We have recently
developed a mouse model, based on the Collaborative Cross strain CC011, for establishment of EBOV
persistence in the male reproductive tract. The objective of this proposal is to investigate EBOV dissemination
and invasion of the testis and epididymis in an immunocompetent mouse model. In addition, we will use this
model to reactivate persisting virus to study recrudescence and the potential of sexual transmission. The central
hypothesis is that our recently developed mouse model for EBOV persistent infection will capture and track
the dissemination and invasion strategy of EBOV infection of the male reproductive tract by identifying key
target cells and determining virus-host signature networks after acute infection has been cleared. Our two
specific aims are: 1) Modeling the Kinetics and the Pathways of EBOV Persistence in the Male Reproductive
Track in Collaborative Cross Strain CC011. 2) Modeling Ebola virus Reactivation and Recrudescence in the
Male Reproductive Tract in Collaborative Cross Strain CC011. We will pursue these aims through a
comprehensive collaboration of diverse, complementary expertise in filovirology and viral pathogenesis,
veterinary pathology, and system genetics. Our methodology includes in vivo and in vitro studies with our well-
defined EBOV mouse model, histopathology and tissue imaging, and single cell and spatial transcriptomics, to
define the spatial and temporal establishment of EBOV persistence and reactivation/recrudescence. The
proposed research is highly significant, because it will 1) provide a framework for the assessment of the spatial
and temporal key target cells and pathways of EBOV invasion into the male reproductive tract, 2) determine the
virus-host signaling networks during the invasion and persistent infection of the testis and the epididymis, and
3) lay the groundwork for the establishment of an animal model for EBOV sexual transmission. The proximate
expected outcome is to understand the entry way for EBOV persistence in the male reproductive tract, and
the development of an EBOV reactivation and recrudescence model. The results will have an immediate
important and long-term impact on our understanding of EBOV persistence and recrudescence and lay the
groundwork for development of potential novel therapeutic targets for prevention of chronic EBOV infection.
```



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