Penn scientists identify viral products that defend against respiratory syncytial virus

Scientists at the University of Pennsylvania have identified a subset of viral products that elicit a strong immune response against respiratory syncytial virus (RSV), potentially explaining why some patients cannot clear the virus. 

For a very rare subpopulation of young infants, respiratory syncytial virus can cause more serious effects than the mild and acute effects that most of us experience--such as a runny nose, cough, and a fever. Instead respiratory problems ensue, hospitalization may be necessary and chances of asthma later in life are increased.

The subset of viral products are called immunostimulatory defective viral genomes (DVGs), and were traditionally thought to be nothing more than an artifact ever since an in vitro experiment conducted in 1940 concluded thusly. However, the present study believes DVGs to be a gateway through which a beneficial immune response can be mounted.

Carolina Lopez, a senior author of the study and assistant professor at Penn, said: "What we see is that DVGs are key in signaling the immune response to turn on. This is the first study that shows that DVGs can critically impact the outcome of an RSV infection and that they are present in infected humans." 

In the study, they show that mice infected with a modified RSV in which the DVGs were deleted experienced a worse disease outcome, including weight loss and inflammation in the lungs. Mice with this modified RSV also expressed higher levels of antiviral genes than mice with the DVG-containing RSV.  

Taking this finding into a human cell line, they established whether RSV with higher levels of DVGs significantly triggered the expression of interferon genes--an important antiviral family of genes. 

They used respiratory secretions from 41 children with confirmed RSV infections and detected DVGs in half of the patients, with a corresponding higher expression of antiviral genes in the respective samples. 

In a subsequent experiment they took lung tissue from 7 deceased donors and exposed slices of lung to RSV. They find the same result to be true--that lungs exposed to RSV with high levels of DVGs had lower levels of viral replication along with a higher antiviral gene expression profile. They found variations between samples suggesting individual differences to DVG accumulation and viral defense. 

Lopez's next step is to understand what factors are responsible that modulate this response to DVGs, giving the researchers the ability to predict the response to the virus between patients. She said: "We have very few tools to manage RSV infection, so we'd obviously like to see if we can figure out a way to trigger an immune response and clear infection before any damage is done. That is the future."

- here's the release
- read the research article

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