The study, conducted by researchers at Yale School of Medicine, also identified the mechanism by which viruses and cigarette smoke interact to increase lung inflammation and damage.
Their experiments showed that the immune systems of mice exposed to cigarette smoke from as little as two cigarettes a day for two weeks overreacted when they were also exposed to a mimic of the flu virus.
The mice's immune systems cleared the virus normally but the exaggerated inflammation caused increased levels of tissue damage.
"The anti-viral responses in the cigarette smoke exposed mice were not only not defective, but were hyperactive," said Jack A. Elias, M.D., the Waldermar Von Zedtwitz Professor of Medicine and chair of internal medicine at Yale School of Medicine.
"These findings suggest that smokers do not get in trouble because they can't clear or fight off the virus; they get in trouble because they overreact to it.
"It's like smokers are using the equivalent of a sledge hammer, rather than a fly swatter, to get rid of a fly," he added.
Elias and his colleagues also found that mice with viral infections that had been exposed to cigarette smoke had accelerated emphysema and airway scarring.
They also defined the signaling pathway that mediates this exaggerated innate immune response.
"If the exaggerated responses are verified in human studies, it will be the first explanation for why viral infections are more serious in smokers," said Elias.
"Once verified, we can find ways to prevent the destruction of lung tissue and the higher illness and death among smokers," he added.
James P. Kiley, director, Division of Lung Diseases of the National Heart, Lung, and Blood Institute, said: "These studies have identified molecular pathways that can explain how cigarette smoke exposure and viral infections interact to make breathing problems worse in diseases like COPD," said
"With further research, these findings may even lead to more effective drug treatments for COPD," he added.
The study is published in the Journal of Clinical Investigation.