# Intersection of Severe Respiratory Infection and Viral Latency

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $635,732

## Abstract

PROJECT SUMMARY/ABSTRACT
The role that chronic viral infection plays in shaping the immune system and responses to subsequent
infections is critically important but understudied. It is estimated that >80% of adults harbor at least 5 latent
herpesviruses. Gammaherpesviruses establish latency in immune cells, further highlighting the importance of
understanding how latency impacts host immune responses to subsequent infections. Currently there is a
substantial knowledge gap in the role played by latency and/or mechanisms by which prior gammaherpesvirus
infection contributes to subsequent immune responses, particularly in the lung. Despite the known deleterious
effects of herpesvirus infection on human health, emerging evidence suggests the possibility the latent
herpesvirus infection may actually protect from secondary infections.
Therefore, to uncover key mechanisms by which latency impacts subsequent immune responses, I propose
the following: I will test the premise that gammaherpesvirus latency impacts host protection during subsequent
pulmonary infections that are prevalent across Kingdoms and dissect how latently infected immune cells
intrinsically respond to heterologous pathogens. I will also delineate the impact of the microbiota on
establishment and maintenance of herpesvirus latency given the critical impact of the microbiota on immune
responses and the broad use of potent antibiotics in medical practice. These distinct but equally important
directives will fill key knowledge gaps.
At the completion, I expect to define the role of latency and reactivation on human immune responsiveness
and develop a framework to define how the balance between microbiota and secondary infections are informed
by latency. Moreover, this study is clinically relevant and fundamentally significant as these findings have the
potential to define novel mechanisms and pathways important for pathogen control and tissue repair.
In alignment with the Stephen I. Katz funding mechanism, this proposal represents a new direction for my
research program. While I have previously studied cytokine regulation of herpesvirus latency during my
doctoral thesis and identified protective microbial metabolites in pulmonary infection as a postdoctoral fellow, I
have not investigated how viral latency intrinsically impacts immune cell function during secondary pulmonary
infections or how the microbiota influences the establishment and maintenance of latency. This new
investigation will require acquisition of novel tools and technologies that will reshape my research program and
enhance its scope and impact. I am perfectly positioned to direct and execute this unique line of investigation
as I have expertise across multiple relevant domains including virology, microbiology, immunology, and critical
care medicine. Additionally as an Early Stage Investigator, I have established collaborations with experts
across diverse domains of microbial pathogenesis.

## Key facts

- **NIH application ID:** 10850232
- **Project number:** 1R01AI181923-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Ashley Steed
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $635,732
- **Award type:** 1
- **Project period:** 2024-06-12 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10850232

## Citation

> US National Institutes of Health, RePORTER application 10850232, Intersection of Severe Respiratory Infection and Viral Latency (1R01AI181923-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10850232. Licensed CC0.

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