# How does Cytomegalovirus use interferon lambda for optimal spread

> **NIH NIH R21** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2022 · $243,540

## Abstract

Project Summary
Although largely asymptomatic, human cytomegalovirus (HCMV) can cause severe and even fatal disease in a
subset of susceptible individuals. The large genome of HCMV allows it to devote a number of its gene products
to optimizing conditions for replication in the host cell and combat cellular stress and antiviral responses. In
some cases, HCMV even exploits these responses to promote infection. The host interferon system, consisting
of Type I (T1, a, b, e, k, w), II (T2, g) and III (T3, l 1-4) interferons, has evolved to mediate innate antiviral
immunity. However, we found that treatment with Type III interferons, which antiviral effects against a number
of viruses including influenza and West Nile viruses, actually enhances the spread of HCMV in both fibroblasts
and epithelial cells. These in vitro results were confirmed using an animal model for cytomegalovirus. Lower
levels of MCMV infection were detected in several organs of mice lacking the IFN-l receptor when compared
to wildtype mouse, confirming a role for IFN-l in promoting cytomegalovirus infection and spread. The
experiments in this proposal will define the mechanism for IFN-l-dependent enhancement of cytomegalovirus
infection using both in vitro and in vivo systems. This will be done in two specific aims. The first aim will define
the pathways involved in proviral IFN-l signaling and how they differ from those that confer an antiviral
environment. The second aim will delineate the properties of IFN-l during in vivo infection, including defining
the cellular source of IFN-l production and identifying the cellular and molecular IFN-l-targets that mediate
the proviral effect. Overall, these studies will define the mechanism by which cytomegaloviruses utilize a
normally antiviral signaling response to enhance spread. These results will provide the basis for additional
studies investigating the potential for therapeutic intervention of this clinically relevant process.

## Key facts

- **NIH application ID:** 10429668
- **Project number:** 1R21AI169180-01
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Nicholas J Buchkovich
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $243,540
- **Award type:** 1
- **Project period:** 2022-01-21 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10429668

## Citation

> US National Institutes of Health, RePORTER application 10429668, How does Cytomegalovirus use interferon lambda for optimal spread (1R21AI169180-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10429668. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*