A study published in PLoS Genetics has tracked the body's response to the H3N2/Wisconsin strain of the flu virus at the genetic level. The researchers injected the virus into 17 volunteers and analysed gene expression patterns from the time of injection to the onset of full-blown clinical symptoms.
The data, which covers 22,000 genes across the volunteers, showed two distinct patterns of gene activation emerging within the population – one group developing symptoms of flu while the other remained asymptomatic.
'The persistent patterns that came out of this were striking, to say the least', said lead researcher Dr Alfred Hero from the University of Michigan, USA.
The white blood cells in our immune system recognise invading pathogens using proteins on their surface known as pattern-recognition receptors (PRR). In this study, symptomatic patients show a strong PRR response, which results in activation of genes involved in inflammation and the production of reactive oxygen species (ROS). The cell damage caused by ROS is what produces the classical symptoms of flu, such as high fever and muscle aches.
In comparison, the asymptomatic volunteers showed little PRR activation. Instead the team found two genes, SOD1 and SOK1, were activated. These genes repress those involved ROS formation. Both groups showed similar amounts of neutralising antibody, indicating a minimal role for antibodies in the early stage of infection.
'This is very important science, really Star Trek stuff. It has very big implications for many infectious diseases, not only flu', said Professor Peter Openshaw, of the Centre for Respiratory Infection at Imperial College, who was not involved in the study.
A further distinction between the two groups is in the levels of protein synthesis – cells in symptomatic patients shut down their protein machinery in the mid-to-late stages of infection, whereas asymptomatic adults actually increase their levels of protein synthesis, resulting in the production of more white blood cells.
'It points out, importantly, that remaining asymptomatic in the face of an exposure to the virus is an active process in the immune system', said Dr Geoffrey Ginsburg, a co-author on the study.
While this work provides some crucial clues to gene behaviour during a flu infection, and might even form the basis of an early warning detection system in the event of a large-scale outbreak, the mystery of the flu infection is far from solved. Other factors like lifestyle and pre-existing stress levels may contribute to the onset of infection and different strains of the virus may also provoke difference response patterns.