In findings that may lead to better ways of preventing and treating influenza and other viral infections, researchers report the discovery of a family of naturally occurring antiviral agents in human cells.
In experiments in human, chicken and mouse cells, these flu-fighting proteins prevented or slowed most virus particles from infecting cells at the earliest stage in the virus lifecycle. The antiviral action happens sometime after the virus attaches itself to the cell and before it delivers its pathogenic cargo.
“We’ve uncovered the first-line defense in how our bodies fight the flu virus,” said Howard Hughes investigator Stephen Elledge, the Gregor Mendel professor of genetics and of medicine at HMS and Brigham and Women’s Hospital. “The protein is there to stop the flu. Every cell has a constitutive immune response that is ready for the virus. If we get rid of that, the virus has a heyday.”
“When we knocked the proteins out, we had more virus infection,” said Abraham Brass, an HMS instructor in medicine at Massachusetts General Hospital, who led the study first as a postdoctoral fellow in the Elledge research group and then in his own lab at the Ragon Institute of MGH, MIT and Harvard. “When we increased the proteins, we had more protection.”
One versatile protein in the small family protected against several human viruses—H1N1 and other influenza A strains, West Nile virus and dengue virus.
The most distinctive property of the protein family is its baseline preventive action before the virus can fuse with the cell, said coauthor Michael Farzan, HMS associate professor of microbiology and molecular genetics at the New England Primate Research Center. “The cell is already primed against the virus,” he said.
The flu-fighting squad is called interferon-inducible transmembrane proteins (IFITM). The proteins double their efforts after infection. “Interferons gave the cells even more protection, but not if we took away the antiviral proteins,” Brass said. The study was published online Dec. 17 in Cell.
For more information, students may contact Abraham Brass at abrass@partners.org, Stephen Elledge at selledge@genetics.med.harvard.edu or Michael Farzan at michael_farzan@hms.harvard.edu.
Conflict Disclosure: The authors declare no conflicts of interest. Brigham and Women’s Hospital and Massachusetts General Hospital have filed a U.S. patent application for this technology that relates to the identification and use of host factors to modulate viral replication and growth.
Funding Sources: Howard Hughes Medical Institute, the Phillip T. and Susan M. Ragon Foundation, the National Institutes of Health, New England Regional Center of Excellence for Biodefense, Cancer Research UK, the Wellcome Trust and the Kay Kendall Leukemia Foundation; the authors are solely responsible for the content of this work.
