School of Medicine scientists are investigating a new way to fight the flu.
Funding has been received largely through the American Recovery and Reinvestment Act (ARRA) to establish a drug discovery center that will look for compounds that enhance the body’s natural virus-killing mechanisms to overcome the flu.
Holtzman
Each year, government agencies work with scientists to develop new flu vaccines to block large-scale flu outbreaks. The vaccines have to be modified yearly because flu viruses constantly change their basic components so the body’s immune system can’t recognize them.
But the researchers, headed by Michael J. Holtzman, M.D., believe they can identify drugs that enhance the body’s resistance to a large range of respiratory viruses. That means these drugs could prevent or treat many different seasonal flu viruses and the 2009 H1N1 flu virus as well as the common cold and other respiratory viruses.
The ARRA provided nearly $2.5 million through the National Institute for Allergy and Infectious Diseases to support this research.
“In past research, we’ve shown that we can defeat flu viruses in mice and in human cells by genetically modifying the interferon-signaling pathway so that it’s more effective in fighting viral infections,” said Holtzman, the Selma and Herman Seldin Professor of Medicine and director of the Division of Pulmonary and Critical Care Medicine. “So now we are trying to develop drugs that would mimic the effects that we saw in mice and cells.”
Interferon signaling is one of the main ways the body stops virus infections. Interferons secreted by infected cells set off a series of responses that activate virus-attacking immune cells and help stop viral replication. Holtzman and his colleagues found a way to ramp up interferon-signaling mechanisms in mice and protect them from respiratory virus infection.
Then the scientists studied which genes became more active in mice and human cells when they enhanced the interferon-signaling pathway. With the new funding, they are taking the next step and building automated systems to look for drugs that replicate the effect of turning on those genes.
“We call it genome-guided drug screening — a new method of drug development that is being done in very few places in the world,” Holtzman said. “We’re putting together a specialized high-throughput system using robotic equipment that can very rapidly screen many different compounds.”
Holtzman and his colleagues are defining the body’s response to the 2009 H1N1 virus. They are using human airway cells grown in the laboratory to understand why the virus is pathogenic and what is unique about its way of infecting its host.
“The virus has a way of subverting the body’s antiviral response,” Holtzman said. “By analyzing the genes whose activity changes when the virus infects cells, we can find genes responsible for infection and resistance.”
This information will feed into the genome-guided drug screening system to identify drugs effective against the 2009 H1N1 flu virus.