Researchers discover the causes for the severity of RSV illness

Approximately one-half of all infants are infected with the respiratory syncytial virus (RSV) during the first year of life, and almost all children have been infected at least once by the time they reach their second birthday. Researchers at West Virginia University have discovered what makes RSV such a severe and persistent illness.

Senior author Giovanni Piedimonte, M.D., and his team have discovered that RSV prompts the release of a molecule that keeps the invaded cells alive despite the infection. The mechanism allows infected cells to survive for a longer period of time while they continue to produce viral particles, thus contributing to the severity and persistence of the infection.

Research results are published in the current issue of the journal PLoS ONE.

Inflammation of the airways caused by RSV often results in wheezing, cough and respiratory distress, creating the most common respiratory infection in infancy or childhood. Each year, an estimated 125,000 infants in the United States are hospitalized with RSV, the leading cause of infant hospitalization.

"There is still no effective therapy or medical treatment for RSV infection. While often mild, it still is responsible for the deaths of hundreds of infants in the United States each year," said Dr. Piedimonte, chair of the WVU Department of Pediatrics and physician-in-chief of WVU Children's Hospital. "The virus also strikes in nursing homes and causes deaths in the elderly population, so understanding how it works is critical."

Piedimonte said up to 500 infants may die of the infection each year. RSV may also predispose children to long-term health problems such as asthma. Other groups at high risk for severe RSV disease include the elderly, adults with underlying respiratory or cardiac disease, and those with a compromised immune system.

"Viruses must find a way to survive inside the host, and in this case RSV has found a way of keeping alive the cells that they infect," Piedimonte explained. "The virus invades the cell, which then produces a small molecule called NGF, or nerve growth factor. NGF allows the cell to survive while the virus reproduces itself. Finally, the cell explodes releasing new viral particles ready to infect the neighboring cells."

In determining how the virus instructs the infected cell to prolong its life, the researchers may have established a blueprint for development of new anti-viral drugs aimed at interfering with the action of NGF, Piedimonte said. He added that RSV may prefer the lower respiratory tract specifically because the smaller airways there allow for more efficient production of NGF.

"The interesting part of the RSV infection is that the viruses induce NGF production within an hour of coming into contact with the human cells - that is, even before they start multiplying," said the paper's lead author, Sreekumar Othumpangat, Ph.D., a researcher in the WVU Pediatric Research Institute.

Children born prematurely as well as those with chronic lung or heart disease are at higher risk for severe RSV infections.

The laboratory studies were done using human cells. Now that Piedimonte's team has discovered how RSV prolongs the life of its host cell, they are proceeding with other studies to see if they can pinpoint the same mechanism in common cold and influenza viruses.

The paper's other authors are Laura F. Gibson, deputy director of the Mary Babb Randolph Cancer Center at WVU, and Lennie Samsell, a research assistant in the Pediatric Research Institute.