# Molecular Neuro-pathogenesis of Congenital Cytomegalovirus Infection

> **NIH NIH SC1** · HOWARD UNIVERSITY · 2021 · $377,500

## Abstract

PROJECT SUMMARY/ABSTRACT Human cytomegalovirus (HCMV) infection is the leading infectious cause
of congenital disorders in newborns. Congenital HCMV infection causes permanent neurological and
neurocognitive disabilities and results in significant health problems worldwide. Our preliminary findings reveal
that Notch pathway is affected by HCMV infection and probably via interaction with CMV-encoded protein, IE1.
Therefore, we propose to explore the molecular pathogenic mechanism via Notch pathway underlying
abnormal brain development caused by congenital CMV infection. This proposed approach is fundamentally
different from previous studies because we apply our unique technologies to explore the mechanisms that
CMV employs to interfere with the brain development of embryos. We will apply the in vitro HCMV infection
system, in utero electroporation system for mouse CMV (MCMV) gene delivery, conditional transgenic mouse
model, and intraplacental MCMV infection system. Our long-term goal is to reveal the mechanisms underlying
CMV-induced congenital neurodevelopmental disorders and develop potential anti-CMV therapeutics. We
hypothesize that the coordinative interaction between CMV and Notch signaling is the key to causing
developmental defects of infected neural progenitor cells (NPCs) in embryos, resulting in permanent
neurological and intellectual disabilities. The hypothesis is supported by our preliminary data and publications
from in vitro and in vivo experiments that HCMV infection affects Notch signaling, that Notch signaling is
involved in CMV-caused defects of NPC proliferation, that IE1 is essential and sufficient to inhibit NPC
proliferation, and that IE1 interacts with proteins of Notch signaling pathway. We will test our hypothesis via the
following Specific Aims: Aim 1. To examine molecular mechanisms for how HCMV IE1 causes defects of
human NSC/NPC proliferation and differentiation in cell culture; and Aim 2. To examine how the CMV IE1
causes different stages of neurogenic defect using an IE1-inducible transgenic mouse model and a clinically-
relevant intraplacental MCMV infection mouse model. We believe that the present proposal is innovative in
several points: First, this is one of the first studies that uses an inducible transgenic mouse model introducing a
specific CMV protein, IE1, to address molecular mechanisms underlying congenital CMV infection. Second, we
study the congenital CMV infection pathology from molecular levels to behavior levels. Lastly, investigators
with different professional backgrounds (virology and neuroscience) are working together to address an
important question with high medical impact. Positive impacts will include qualitative advances in
understanding molecular virology and CMV pathobiology in particular, and that understanding the mechanisms
CMV uses to cause neural defects may thus drive development of new, selective anti-CMV therapeutic
strategies.

## Key facts

- **NIH application ID:** 10222529
- **Project number:** 5SC1AI112785-08
- **Recipient organization:** HOWARD UNIVERSITY
- **Principal Investigator:** Qiyi Tang
- **Activity code:** SC1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $377,500
- **Award type:** 5
- **Project period:** 2014-08-07 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10222529

## Citation

> US National Institutes of Health, RePORTER application 10222529, Molecular Neuro-pathogenesis of Congenital Cytomegalovirus Infection (5SC1AI112785-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10222529. Licensed CC0.

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