# Development of antibodies to specific cell surface markers to assess macrophage polarization during Adenovirus 14 and 14p1 infection in the Syrian hamster

> **NIH NIH R03** · IDAHO VETERANS RESEARCH / EDUCATION FDN · 2023 · $62,300

## Abstract

PROJECT SUMMARY
Adenovirus (Ad) normally induces mild, self-limited infections in immunocompetent human hosts. A more virulent
strain of Ad14, Ad14p1, first emerged in the U.S. military and has since spread globally to civilian populations
resulting in severe infections, sometimes leading to acute respiratory distress syndrome (ARDS). The incidence
of ARDS in the U.S. is ~200,000 cases annually, with a hospital mortality rate of ~40%. Most ARDS treatment
measures target the inflammatory response; however, all have failed to show a mortality benefit. We have shown
that the Ad E1B 20K (20K) gene product controls modulation of the macrophage inflammatory response to cells
dying from Ad infection (Ad CPE corpses). Absent or low level 20K gene expression generates Ad CPE cells
that are pro-inflammatory, whereas normal (wild type virus) 20K gene expression generates anti-inflammatory
Ad CPE cells. Ad14p1 expresses only 20% of the 20K expressed by wild type Ad14. This reduced 20K
expression induces pro-inflammatory Ad14p1 CPE corpses, whereas wild type Ad14 CPE corpses are anti-
inflammatory. The central hypothesis of this application is that this viral genetic change in the immunomodulatory
effect of infection with emergent Ad14p1 is the key biological difference through which this emergent virus
increases the incidence and severity of acute lung injury (ALI) that can result in ARDS and death. The Syrian
hamster, Mesocricetus auratus, is permissive for infection with human adenoviruses. Syrian hamsters are also
susceptible to many other human viruses such as influenza, hantavirus, SARS-CoV, SARS-CoV-2, Marburg and
Ebola. We have shown that infection of hamsters with Ad14p1 replicates many of the key features of human
ALI/ARDS including patchy bronchopneumonia, increased pro-inflammatory cytokine expression, edema and
neutrophil infiltration into the lung and airways. A problem with the Syrian hamster model system has been that
there are no transgenic hamsters and that there is a lack of immunological reagents available, such as those for
the mouse and human. Development of the CRISPR/Cas9 Syrian hamster has removed one of those obstacles.
This project addresses the other problem by creating antibodies that are specific for hamster cell surface markers
expressed on macrophages. These antibodies will allow identification and isolation of macrophage sub-
populations and comparative characterization of macrophage activation in response to Ad14 and Ad14p1
infections. The antibodies will complement the small number of existing hamster-specific antibodies available for
flow cytometry studies. These antibodies will allow us to begin to understand the effects of Ad14 and Ad14p1
infection on the innate immune response and to develop mechanistic studies of how these two viruses generate
such different immune responses. Understanding those key factors will allow development of targeted
therapeutics to treat not only Ad-induced ALI/ARDS but potentially ARDS trigger...

## Key facts

- **NIH application ID:** 10725702
- **Project number:** 1R03AI178251-01
- **Recipient organization:** IDAHO VETERANS RESEARCH / EDUCATION FDN
- **Principal Investigator:** Jay R Radke
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $62,300
- **Award type:** 1
- **Project period:** 2023-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10725702

## Citation

> US National Institutes of Health, RePORTER application 10725702, Development of antibodies to specific cell surface markers to assess macrophage polarization during Adenovirus 14 and 14p1 infection in the Syrian hamster (1R03AI178251-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10725702. Licensed CC0.

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