# The role of viral chemokines for CMV dissemination and congenital infection

> **NIH NIH P01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $500,646

## Abstract

ABSTRACT – PROJECT 2
Congenital cytomegalovirus (cCMV) infection is the leading infectious cause of congenital defects and the
development of vaccines and treatments to prevent cCMV have long been recognized as top public health goals.
Unfortunately, vaccines targeting human CMV (HCMV) glycoproteins or based on attenuated HCMV have not
yet yielded a licensed vaccine, most likely since they were unable to provide immunity against infection that is
better than the limited immunity provided by natural infection. The overall goal of this project is to explore a
novel and innovative approach to prevent cCMV infection by targeting the function of viral chemokine-like
proteins. This approach is based on the suprising finding that rhesus CMV (RhCMV) lacking the UL146 family of
viral CXC chemokine-like proteins shows highly limited dissemination, reduced plasma viremia and delayed
shedding during primary infection of rhesus macaques (RM). Since viral dissemination is essential for congenital
infection, we hypothesize that UL146 family members are required for transmission to the fetus, and that
interfering with their role in dissemination could prevent congenital infection. The goals of this project are
therefore to identify and characterize the UL146 family proteins required for dissemination and congenital
infection and to develop UL146 family targeting strategies to prevent congenital infection. In Aim 1 we will
determine which of the six RhCMV UL146 family proteins are required for dissemination, and whether HCMV
UL146 and/or UL147 can substitute for their RhCMV homologs. Since this family displays homology to host
chemokines, we will also examine the chemokine structural requirements for dissemination. We will begin
characterizing possible mechanisms of dissemination by studying UL146-mediated spreading in placental
organoid cultures and by characterizing how the cellular microenvironment is affected by viral chemokines using
immunohistochemistry and single cell transcriptomics and proteomics. In Aim 2 we will examine dissemination
of UL146 family-deleted RhCMV to tissues upon intravenous inoculation during primary infection and
transmission to the fetus in CD4+ T cell depleted dams. We will additionally examine whether the minimal set of
UL146 family members required for dissemination can restore congenital infection. In Aim 3 we will evaluate
whether UL146 family proteins are immunogenic during primary infection and whether immunization against the
minimal set of UL146 family members required for dissemination will limit dissemination upon primary infection.
Finally, we will determine whether IgG from these immunized animals can protect against congenital infection,
either on their own or in combination with IgG treatments evaluated in Project 3. We expect that a limited number
of UL146 family members support viral dissemination and congenital infection and that anti-UL146 immunity can
limit dissemination and congenital infection. By providing a be...

## Key facts

- **NIH application ID:** 10874239
- **Project number:** 2P01AI129859-07
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Klaus J Fruh
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $500,646
- **Award type:** 2
- **Project period:** 2019-07-24 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10874239

## Citation

> US National Institutes of Health, RePORTER application 10874239, The role of viral chemokines for CMV dissemination and congenital infection (2P01AI129859-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10874239. Licensed CC0.

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