Penn Vet study shows how respiratory virus triggers its own demise
Parents of newborns—especially those born during the winter months—are vigilant in protecting their babies from any source of infection. But despite their best efforts, some infants fall ill to respiratory syncytial virus, better known as RSV. In most cases, this manifests as a run-of-the-mill cold, but a percentage of infants, as well as some elderly people, can develop serious respiratory problems as a result of an RSV infection.
“If you go and talk to clinicians,” says Carolina López, an assistant professor of pathobiology in the School of Veterinary Medicine, “they’ll say there are very different outcomes of an RSV infection and there is no good way to predict how a given patient will do when they walk into the hospital.”
In a new study published this month in PLOS Pathogens, López and colleagues describe what appears to be a key factor influencing how individuals respond to an infection with RSV. They found that defective viral genomes, or DVGs, which are produced by the virus itself during replication, elicit an immune response in people who were infected. The finding may one day help clinicians better predict patient outcomes. It also opens the possibility of manipulating DVGs to allow a patient to more quickly clear a virus from his or her system.
The researchers used mice to show that viruses lacking DVGs caused more severe forms of RSV. Mice infected with the modified viruses also had lower expression of genes involved in an anti-viral immune response. The scientists observed similar patterns in a human cell line.
Next López’s team examined samples of respiratory secretions collected from patients diagnosed with RSV at the Children’s Hospital of Philadelphia. They detected DVGs in about half of the samples; those samples also had higher levels of anti-viral gene expression.
Finally, the researchers exposed lung tissue from deceased donors to two versions of RSV. The tissue infected with RSV containing high levels of DVGs had lower levels of viral replication and higher expressions of antiviral genes, again suggesting that the DVGs were somehow triggering the anti-viral response.
“If you put a virus containing a lot of these defective genomes into human lung samples, they all respond,” López says, “but the difference was some patients’ tissue could accumulate the DVGs faster than others and that correlated with outcome. That tells you that there are host factors that modulate this response to DVGs and that could predict outcomes. So now we want to find out what those host factors are.”
Knowing that, she says, could give clinicians a tool to effectively manage RSV.