# Genetic Pathways of Human Cytomegalovirus Drug Resistance

> **NIH NIH R01** · PORTLAND VA RESEARCH FOUNDATION, INC. · 2022 · $130,000

## Abstract

Project Summary
Toxicity and drug resistance limit the efficacy of antiviral therapy for cytomegalovirus
(CMV) disease in immunosuppressed hosts such as cancer and transplant recipients.
Current therapy includes DNA polymerase inhibitors ganciclovir, foscarnet and cidofovir.
The terminase inhibitor letermovir was recently approved for prophylaxis, and the UL97
kinase inhibitor maribavir has completed Phase 3 trial as alternative therapy. In clinical
practice, CMV drug resistance cannot be diagnosed by direct phenotypic testing of viral
isolates, and instead is dependent on an accurate correlation of detected viral mutations
and associated resistance phenotypes. The objective of this research is to determine the
genetic mechanisms of CMV drug resistance in order to improve clinical diagnosis and
the development of new antivirals. Many resistance mutations and polymorphisms in the
CMV UL97 kinase, UL54 DNA polymerase and UL56/UL89/UL51 terminase genes have
been and continue to be phenotyped, with diagnostically important new resistance loci
being identified during each project period. Technical advances in recombinant
phenotyping and whole genome deep sequencing are facilitating this research. In the
upcoming project period, new focus areas include the characterization of mutations
selected after drug exposure in genes outside of known antiviral targets, and analysis of
the effects of baseline viral strain variation on drug susceptibility. Specific aims are (1)
study the evolution and phenotypes of CMV mutations that develop after in vitro or in
vivo exposure to antiviral compounds and combinations; (2) evaluate the phenotypic
significance of genetic changes identified by viral whole genome deep sequencing that
are outside of known antiviral target genes, and (3) determine the impact of baseline
viral strain on drug susceptibility phenotypes by characterization of alternative viral
clones and host cells.

## Key facts

- **NIH application ID:** 10444134
- **Project number:** 2R01AI116635-06A1
- **Recipient organization:** PORTLAND VA RESEARCH FOUNDATION, INC.
- **Principal Investigator:** Sunwen Chou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $130,000
- **Award type:** 2
- **Project period:** 2015-08-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10444134

## Citation

> US National Institutes of Health, RePORTER application 10444134, Genetic Pathways of Human Cytomegalovirus Drug Resistance (2R01AI116635-06A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10444134. Licensed CC0.

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