# Determinants of acute and persistent Zika virus shedding in semen

> **NIH NIH R21** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2024 · $190,684

## Abstract

Project Summary
Zika virus (ZIKV) causes congenital ZIKV syndrome in infants exposed in utero following maternal ZIKV
infection via mosquito bite or sexual transmission during pregnancy. It is estimated that 3-23% of ZIKV cases
are due to sexual transmission. More than half of ZIKV-infected men shed ZIKV in semen, and some men shed
ZIKV in semen for up to 6 months post-disease onset. In human semen, ZIKV infects several cell types
including epithelial cells and immune cells. Using a mouse model, infection of epididymis epithelial cells has
been shown to be critical for acute ZIKV shedding in semen. The role of immune cells in ZIKV shedding in
semen is unknown, though we detected persistent ZIKV infection within the epididymal lumen, rather than the
epididymis epithelium, suggesting immune cells may be critical for persistent ZIKV shedding. The most closely
related virus to ZIKV, Spondweni virus (SPOV), is poorly shed in semen despite dissemination to the male
reproductive tract. ZIKV containing the prM/E structural genes from SPOV is shed in semen at significantly
lower levels during acute infection. The long-term goal of this project is to understand the mechanisms of ZIKV
shedding in semen and sexual transmission. The objectives of this study are to identify the viral factors and cell
types that contribute to acute and persistent viral shedding in semen. The hypothesis is that ZIKV shedding in
semen is driven by viral structural genes and persistent infection of immune cells in the male reproductive tract.
Two specific aims will address this hypothesis: 1) Determine the role of viral structural genes in acute ZIKV
shedding in semen; and 2) Determine the role of immune cells in persistent ZIKV shedding in semen. In the
first aim, we will use our reverse genetics system to generate a reverse genetics system for SPOV and a
chimera containing ZIKV prM/E structural genes within SPOV. Viruses will be used to infect male mice, and
viral shedding in ejaculates will be measured. Cell types differentially infected within the epididymis epithelium
will be identified. In the second aim, macrophages will be depleted from ZIKV-infected mice during acute and
persistent infection. Viral shedding in semen and infection of the epididymis will be measured. The research
proposed here is innovative because it assesses ejaculates, which are biologically relevant samples for sexual
transmission, and a novel role for immune cells in ZIKV sexual transmission. Upon successful completion of
the proposed research, the anticipated contribution of this work will be the identification of the flavivirus factors
that dictate viral shedding in semen and the cell types that contribute to viral shedding in semen. This
contribution is expected to be significant because it will increase our understanding of how viruses are sexually
transmitted.

## Key facts

- **NIH application ID:** 10878331
- **Project number:** 1R21AI183178-01
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Nisha Duggal
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $190,684
- **Award type:** 1
- **Project period:** 2024-06-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10878331

## Citation

> US National Institutes of Health, RePORTER application 10878331, Determinants of acute and persistent Zika virus shedding in semen (1R21AI183178-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10878331. Licensed CC0.

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