# The role of the innate immune response in adenovirus Ad14p1 immunopathogenesis

> **NIH NIH P20** · IDAHO VETERANS RESEARCH / EDUCATION FDN · 2020 · $224,221

## Abstract

PROJECT SUMMARY (See instructions): 
Background: Adenovirus (Ad) infection normally induces mild, self-limited disease in immunocompetent 
human hosts. A new strain of Ad14, Ad14p1, first emerged in U.S. military and has since spread globally to 
civilian populations resulting in severe infections leading to acute respiratory distress syndrome (ARDS). We 
have shown that Ad that lacks expression of the E1B 20K (20K) gene results in dead cells (Ad CPE corpses) 
that stimulate a pro-inflammatory response from macrophages compared to an anti-inflammatory response 
from wild type Ad. Ad14p1 expresses only 20% the amount of 20K as the prototype Ad14 and results in Ad14p1 
CPE corpses that are pro-inflammatory while prototype Ad14 CPE corpses are anti-inflammatory. Infection of 
Syrian hamsters (permissive for human Ad) showed a patchy bronchopneumonia following infection with 
Ad14p1 compared to little inflammation with Ad14. Hypothesis: 20K-dependent changes in miRNA 
expression regulate Ad CPE corpse immunomodulatory activity leads to increased pathogenesis. Specific 
Aims: 1. To refine and further develop the Syrian hamster model of Ad14p1 immunopathogenesis. 2. To 
determine the roles of alveolar macrophages and T-cells in Ad14p1 immunopathogenesis in the Syrian 
hamster. 3. To define the 20K expression threshold effect on Ad14p1 immunopathogenesis. 4. Define the 
expression of ‘Find Me’, ‘Eat Me’ and ‘Don’t Eat Me’ signal expression of Ad14/Ad14p1 CPE corpses and their 
roles in immunorepression. 5. Determine the role of increased expression of miR-181a-5p as the mediator of 
Ad14 CPE corpse repression on markers of pro-inflammatory responses: cytokine expression and M1/M2 
macrophage polarization. Use of HPIC and Flow Cytometry facilities: Aims 1 and 2 will utilize the Syrian 
hamster model of Ad14p1 immunopathogenesis and will make extensive use of the HPIC for tissue fixation, 
embedding and sectioning, routine H&E, immunohistochemistry and pathological scoring of tissues to assess 
differences in disease pathology. All aims will make use of the Accuri C6 and MoFlo XDP that are available in 
the Flow Cytometry facility. Contribution to the Multi-disciplinary Infectious Diseases Research Program: 
Dr. Radke is a respected scientist in the field of adenoviruses and programmed cell death. His experience in 
adenoviruses and Ad14p1 will expand the core’s studies on infectious diseases to the viral pathogenesis while 
is interest in the innate immune response to virally infected and transformed cells will be in step with the core’s 
focus on the innate immune response to infectious diseases. In addition he will provide additional expertise in 
flow cytometry and molecular biology techniques to the core.

## Key facts

- **NIH application ID:** 10134776
- **Project number:** 5P20GM109007-05
- **Recipient organization:** IDAHO VETERANS RESEARCH / EDUCATION FDN
- **Principal Investigator:** j RADKE
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $224,221
- **Award type:** 5
- **Project period:** — → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134776

## Citation

> US National Institutes of Health, RePORTER application 10134776, The role of the innate immune response in adenovirus Ad14p1 immunopathogenesis (5P20GM109007-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10134776. Licensed CC0.

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