# Defective Viral genomes in RSV pathogenesis

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $309,997

## Abstract

Summary
Our laboratory recently revealed a critical role for defective viral genomes (DVGs), which are generated during
most viral infections, as primary inducers of antiviral immunity in response to many respiratory viral infections.
Importantly, detection of DVGs in respiratory secretions from children infected with respiratory syncytial virus
(RSV) correlates with evidence of strong antiviral responses, supporting accumulating evidence of a critical
role for DVGs in regulating the pathogenesis of RSV. However, study of the biology and clinical impact of
DVGs has been slow due, in part, to lack of appropriate technology, and details of the mechanisms that
regulate DVG generation and interaction with the host remain unknown. Here we propose to take advantage of
important technical advances, including our ability to distinguish DVGs from full-length viral genomes at a
single cell level, to significantly improve our understanding of DVG generation and activity during infection with
RSV. This pathogen is the major cause of hospitalizations of infants and can cause severe illness and even
death in the elderly and the immunosuppressed. Our overarching hypothesis is that DVGs are primary
modulators of viral pathogenesis in humans and that their immunostimulatory activity can be harnessed to
minimize viral-associated disease. In this proposal, we will follow up on preliminary data challenging the
current paradigm that DVG generation initiates randomly during virus replication, and will define viral
signatures that regulate the generation of RSV DVGs, thereby advancing strategies to manipulate the DVG
content during infection for research and potential therapeutic gain (Aim 1). In addition, we will take advantage
of our ability to distinguish DVGs from full-length viral genomes within a cell to understand unique DVG-host
interactions that regulate the induction of antiviral immunity during RSV infection (Aim 2). Lastly, we will use
unique cohorts of clinical samples readily available to us, to assess the impact of DVGs on the clinical outcome
of RSV infection and establish the relationship between DVG levels, disease severity, and host response in
humans (Aim 3).

## Key facts

- **NIH application ID:** 10200431
- **Project number:** 7R01AI137062-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Carolina B. Lopez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $309,997
- **Award type:** 7
- **Project period:** 2018-05-03 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200431

## Citation

> US National Institutes of Health, RePORTER application 10200431, Defective Viral genomes in RSV pathogenesis (7R01AI137062-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10200431. Licensed CC0.

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