# Genetic Pathways of Human Cytomegalovirus Drug Resistance

> **NIH NIH R56** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $315,000

## 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 is in late stage 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 enduring objective of this research is to
determine the genetic mechanisms of CMV drug resistance in order to improve clinical
diagnosis and the development of alternate therapies. 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) continued evaluation of 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:** 10455774
- **Project number:** 2R56AI116635-06
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Sunwen Chou
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $315,000
- **Award type:** 2
- **Project period:** 2015-08-13 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10455774

## Citation

> US National Institutes of Health, RePORTER application 10455774, Genetic Pathways of Human Cytomegalovirus Drug Resistance (2R56AI116635-06). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10455774. Licensed CC0.

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