Medical Professional Publications

More Evidence: Viral Infections Leave a Unique “Signature”

Investigators at Nationwide Children’s Hospital have gathered more evidence demonstrating that a single biological sample can indicate the type of virus a child is infected with and the severity of his or her disease course.  Studies have already shown that different viruses cause human immune cells to respond in different ways and that these gene patterns can be identified in blood samples.  These pathogen “signatures” can help discriminate which virus a patient is infected with.
In a study appearing in the Journal of Virology, Nationwide Children’s investigators, led by Dr. Emilio Flano, examined how airway epithelial cells respond to viral infections and to what extent their response is related to system-wide immune responses and disease severity.
Airway epithelial cells line the respiratory tract and serve as first-in-line defenders against respiratory viruses.  Upon infection, these cells produce signaling molecules that trigger inflammation and initiate the immune response in the lung.   “There is compelling evidence that airway epithelial cells are part of local immune responses in the airway, but it is unclear to what extent their response contributes to or forecasts system-wide immune responses,”  says Dr. Flano, principal investigator in the Center for Vaccines and Immunity at The Research Institute at Nationwide Children’s Hospital.

The study details the team’s investigation into how the airway epithelium responds to flu and respiratory syncytial (RSV) virus infection.   In the lab, they challenged human and mouse airway epithelial cells with RSV and flu virus and recorded the cells’ anti-viral responses.  They then compared these responses to gene expression signatures obtained from blood draws of infants admitted to the hospital for RSV bronchiolitis or acute influenza infection. 
They found that the airway epithelium’s response to the flu virus and RSV infection was virus-specific.  The infected cells expressed different genes and secreted different immunological mediators, depending on the virus-type.  The team also found that the “molecular signature” in the airway epithelium correlated with the molecular signature in the blood and with the clinical severity of the disease.
“Our results suggest that airway epithelial cell response to infection relates to systemic immune response and that pathogen-specific molecular signatures are a central component of host defense,” says Dr. Flano.  Dr. Flano says that the existence of system-wide, viral-specific signatures could mean that doctors could gather samples for “signature” testing using methods that are less invasive than blood draws, such as nasal swabbing.
Future studies are needed to analyze the relationship described in this study using airway cells or nasal washes and blood samples from the same patient.
This study is an excellent example of collaboration among The Research Institute’s Centers of Emphasis. The manuscript is the result of collaboration between the Flano Lab (immunology), Ramilo/Mejias Lab (clinical infectious diseases) and the Peeples Lab (virology).

Ioannidis I, McNally B, Willette M, Peeples ME, Chaussabel D, Durbin JE, Ramilo O, Mejias A, Flaño E.  Plasticity and virus-specificity of the airway epithelial cell immune response during respiratory viral infection.  J Virol. 2012 Mar 7. [Epub ahead of print]

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