Double stranded RNA as a non-invasive biomarker of infection
Abstract
Double-stranded RNA (dsRNA) is a newly appreciated species of noncoding RNA made in mammalian cells. We show that thousands of host-derived dsRNAs are produced in healthy mammals (in cultured cells and in vivo), and that the specific dsRNAs produced are consistent between individuals. Importantly, we demonstrate that viral infection changes the population of host dsRNAs produced. For example, infections with influenza virus and vesicular stomatitis virus each upregulate a number of specific host dsRNAs that are unique to each virus infection. In addition, there are certain host dsRNAs that are upregulated in both infections (but not in uninfected controls). dsRNAs are excellent diagnostic markers since 1) many pathogens make specific dsRNA, 2) we have identified host dsRNAs that are diagnostic of infection, and 3) we show that dsRNA is detected in human saliva and blood. Here we propose to collaboratively determine the biomedical significance and diagnostic utility of novel dsRNAs we have identified. Key to our project are new dsRNA isolation methods, access to excellent patient samples and viral stocks, and informative cell culture and animal model systems. We will determine the dsRNAs produced in response to specific viral and bacterial infections. We will establish RTPCR based assays for our discovered biomarker panel. We will explore the presence and persistence of dsRNA biomarkers in infected human saliva and blood. Furthermore, we will demonstrate that we can diagnose specific (known and “unknown”) infections from the pathogen dsRNA or host dsRNA produced. We will also explore the mechanisms of production and regulation of host dsRNA molecules, including in a unique mouse model that we are developing for this purpose.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 16, 2019
- Source ID
- HDTRA11810032
Entities
People
- Sara L. Sawyer
Organizations
- Defense Threat Reduction Agency
- University of Colorado