Researchers from University of Pennsylvania has found that defective viral genomes (DVGs) promotes a strong immune response against respiratory syncytial virus. When respiratory secretions samples from 41 children were analyzed with confirmed confirmed diagnoses of respiratory syncytial virus. They detected DVGs in nearly half of the patients and found that these same samples also contained higher levels of anti-viral genes than those without detectable levels of DVGs. Future research will focus on how to modulate DVGs.
PLoS Pathog. 2015 Sep 3;11(9):e1005122.
Sun Y1, Jain D1, Koziol-White CJ2, Genoyer E1, Gilbert M1, Tapia K1, Panettieri RA Jr2, Hodinka RL3, López CB1.[expand title=”Show Affiliations”]
1Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
2Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
3Department of Pathology and Laboratory of Medicine, Perelman School of Medicine at the University of Pennsylvania and Clinical Virology Laboratory, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.[/expand]
Human respiratory syncytial virus (RSV) is a major cause of severe respiratory illness in children and susceptible adults. Respiratory Syncytial Virus blocks the development of the innate antiviral immune response and can grow to high titers in the respiratory tract. Here we demonstrate that immunostimulatory defective viral genomes (iDVGs) that are naturally generated during Respiratory Syncytial Virus replication are strong inducers of the innate antiviral response to Respiratory Syncytial Virus in mice and humans. Inmice, Respiratory Syncytial Virus iDVGs stimulated the expression of antiviral genes, restricted viral replication, and prevented weight loss and lung inflammation. In human cells, the antiviral response to RSV iDVGs was dominated by the expression of IFN-λ1 over IFN-β and was driven by rapid intranuclear accumulation of the transcription factor IRF1. Respiratory Syncytial Virus iDVGs were detected in respiratory secretions of hospitalized patients, and their amount positively correlated with the level of expression of antiviral genes in the samples. Infection of explanted human lung tissue from different donors revealed that most humans can respond to Respiratory Syncytial Virus iDVGs and that the rate of accumulation of iDVGs during infection directly correlates with the quality of the antiviral response. Taken together, our data establish iDVGs as primary triggers of robust antiviral responses to Respiratory Syncytial Virus and provide the first evidence for an important biological role for naturally occurring iDVGs during a paramyxovirus infection in humans.Go To PLoS Pathog.