27 October 2008

Immune system overdrive responsible for cold symptoms

by Kate Melville

The human rhinovirus (HRV) cops most of the blame for the sneezing and runny nose that we associate with the common cold, but in reality, it's not the virus but its ability to manipulate our genes that causes the most annoying cold symptoms. Now, for the first time, researchers have revealed how HRV hijacks our genes to trigger this overblown immune response, possibly opening the door for new therapeutic treatments for the common cold. "The study's findings are a major step toward more targeted cold prevention and treatment strategies while also serving as a valuable roadmap for the broader respiratory science community," the University of Calgary's David Proud, lead author of the study, told the American Journal of Respiratory and Critical Care Medicine.

For the study, the researchers recruited volunteers who were inoculated with either HRV or a sham inoculation and obtained cell scrapings from the nasal passages 8 and 48 hours after the inoculation. After 8 hours, there were virtually no differences between the control and the HRV-inoculated group, but by the 48-hour mark, more than 6500 genes has been significantly up- or down-regulated in the HRV subjects - many of the more highly up-regulated genes fell into two major categories: genes making antiviral proteins, including viperin; or genes making pro-inflammatory cytokines.

In other words, rhinovirus infection triggered a massive immune response in the nasal mucosa. Because rhinovirus is not as destructive as other more serious viral infections, this response appears to be disproportionate to the threat.

The researchers classified the active genes according to function, and found many involved in a process known as chemotaxis, which recruits various immune cells to the site of infection. These particular genes have been correlated with symptoms such as inflammation, congestion and runny nose. Other groups of active genes have also been classified; among them are genes which make antiviral compounds thought to help thwart infections. "This study shows that after rhinovirus infection, cold symptoms develop because parts of our immune system are in overdrive," said co-researcher Lynn Jump.

The researchers also found that viral titer (load) more than doubled in cells that had had the viperin-producing gene "knocked down," showing that HRV replication was hampered by viperin. "This had never been examined during rhinovirus infections," said Dr. Proud. "Some evidence existed that this protein had effects on influenza, but nothing was known about its role in rhinovirus infections. So it was a bit unexpected."

"Overall these data provide new insights into the host response to HRV infection and identify several novel candidate genes that require further study to clarify their role in disease pathogenesis," concluded Dr. Proud. "This may identify proinflammatory, or host defense pathways that could be targeted for drug development, not only as treatments for colds but also for viral exacerbations of asthma and COPD."

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Source: American Thoracic Society, Procter & Gamble