RSV, labeled with GFP to glow green, infects a sample of lung tissue from a deceased donor. New research shows that the virus produces defective genomes that prompt the immune system to eliminate the pathogen. Credit: University of Pennsylvania
Almost all human beings are exposed to the respiratory syncytial virus, or RSV, before their second birthdays. For most, the symptoms mimic those of the common cold: runny nose, coughing, sneezing, fever. But in some very young infants – and some older adults – the disease can be serious, causing respiratory problems that require hospitalization and increase the risk of developing asthma later in life.
Even in the hospital, doctors can’t do much more than offer supportive care. But, with a new study, PennU reseachers have identified immunostimulatory defective viral genomes, or DVGs, were once thought to have no biological function.
“What we see is that DVGs are key in signaling the immune response to turn on,” said Assistant Prof Carolina López.
When the RSV infects a host and begins to rapidly replicate itself, it produces defective versions of its genome that contain large deletions. DVGs by themselves cannot replicate and, in previous studies by the López lab, had been found in culture to trigger expression of genes responsible for an anti-viral immune response. Yet no one had showed that they had a biological function in humans.
Host-intrinsic factors determine the response to iDVGs in the human lung.
In new work: 1. they found mice infected with a modified RSV that lacked DVGs experienced worse disease symptoms, including weight loss and lung tissue inflammation, and had higher levels of virus in their lungs than mice infected with RSV that had high levels of DVGs. Mice infected with the modified RSV also had lower expression levels of anti-viral genes, such as interferon, than mice infected with the DVG-containing RSV.
2.In human cell line, as with mice, RSV wit higher levels of DVGs potently triggered the expression of interferon genes.
They also analyzed respiratory secretions collected from 41 children with RSV at CHOP. 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.
Also in deceased donor lungs exposed to RSV with high levels of DVGs had lower levels of viral replication and higher levels of antiviral gene expression one day after infection, though there were variations from sample to sample, suggesting that there may be individual differences in how people accumulate DVGs and thus how they defend against the virus.”That tells you that there are host factors that modulate this response to DVGs and that that could predict outcomes. So now we want to find out what those host factors are.” The researchers would also like to investigate ways of manipulating either the DVGs themselves or host factors to improve patients’ response to the virus. http://www.upenn.edu/pennnews/news/penn-study-identifies-viral-product-promotes-immune-defense-against-rsv
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