# The Role of Pulmonary Natural Killer Cells in Cytomegalovirus Induced Pneumonitis

> **NIH NIH F31** · BROWN UNIVERSITY · 2024 · $48,974

## Abstract

Abstract
 Cytomegalovirus (CMV) is a b-herpesvirus that is ubiquitously spread throughout the human
population. CMV is the most common perinatal congenital viral infection among neonates and is also a
common postnatal infection targeting immunocompromised hosts. CMV induced pneumonitis is among the
most common manifestations of infection. Although an abundance of research has been conducted on the
immune response to CMV, the true route of initial infection is still in contention. Through research with murine
CMV (MCMV), it is thought that infection first occurs in the upper respiratory tract, specifically the olfactory
epithelium, with a subsequent primary seeding of susceptible cells in the lung. Traditionally, experiments with
MCMV have utilized systemic infection methods that may not accurately recapitulate in vivo dissemination.
Therefore, re-examination with physiologically relevant viral infection methods are of the utmost importance.
Following intratracheal administration of MCMV, I observed a distinct viral dissemination pattern with viral
replication only occurring in the lung with later salivary gland colonization. This contrasted with intraperitoneal
infection which resulted in robust infection of peripheral tissues, but no lung infection, with later colonization of
the salivary gland. Preliminary data also suggests that following acute respiratory infection, there is an increase
in the frequency of lymphocytes in the lung tissue with an outsized role of Natural Killer (NK) cells in response
to pulmonary CMV as compared to other innate lymphoid cell (ILC) compartments. Based on these data, I
hypothesize that the lung will play a central role in MCMV dissemination, and that ILCs will be heavily involved
in preventing systemic viral dissemination. My first aim will seek to investigate in vivo viral kinetics following
acute respiratory infection. I also aim to investigate the specific NK cell responses in the lung that control viral
dissemination. My initial data suggests an important role for NK cell activation in the lung, with limited survival
observed in animals deficient for Ly49H. To study the role of NK cells in response to respiratory MCMV
infection, I propose to employ a variety of genetic manipulations to selectively remove NK cells, B and T cells,
NK cell activating receptors, and cytokine receptors. Using these various models, I will assess animal survival,
viral prevalence, and immune activation following acute respiratory MCMV infection. These proposed studies
aim to elucidate the mechanisms of immune control of pulmonary CMV infection and may provide insights into
cellular therapies for the treatment of CMV pneumonitis. Additionally, by studying a more physiologically
relevant respiratory CMV infection model, I can gain further insights into the mechanisms of viral dissemination
in the human pathogenesis of CMV. To prepare me for the proposed work, my training has taken place in the
lab of the highly credentialed Laurent Br...

## Key facts

- **NIH application ID:** 10824955
- **Project number:** 1F31HL172690-01A1
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Miles Alexander Mundy
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10824955

## Citation

> US National Institutes of Health, RePORTER application 10824955, The Role of Pulmonary Natural Killer Cells in Cytomegalovirus Induced Pneumonitis (1F31HL172690-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10824955. Licensed CC0.

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