Researchers from The Ohio State University have uncovered new roles for IFITM3, a protein essential for protecting against severe influenza, in preventing virus adaptation and controlling infection thresholds. Their study, published in Nature Communications, highlights the increased vulnerability of individuals deficient in this protein to emerging flu viruses.
IFITM3, or interferon-induced transmembrane protein 3, is a key component of the innate immune system that helps limit the replication of flu viruses. The study, led by Jacob Yount, a professor of microbial infection and immunity, reveals that IFITM3 not only reduces the severity of flu infections but also raises the minimum number of viral particles required to trigger illness. This means that those lacking this protein are more susceptible to infection from even minimal viral exposure.
As reported by medicalxpress, the findings are especially concerning as about 20% of Chinese individuals and 4% of people of European descent carry genetic mutations that impair IFITM3 production. With the Centers for Disease Control and Prevention currently monitoring the spread of H5N1 avian flu, which has infected 45 people globally, understanding these vulnerabilities is crucial.
“An IFITM3 deficiency makes it easier for a low dose of virus to be infectious,” Yount explained. “Our study suggests that without IFITM3, individuals face a higher risk of both infection and aiding viral mutation, particularly with novel strains.”
Yount’s research team used genetically modified mice lacking the IFITM3 gene to demonstrate that a single viral particle could cause infection in these mice, whereas a higher dose was needed to infect normal mice. Further laboratory tests on human lung and immune cells confirmed that silenced IFITM3 genes increased susceptibility to various avian, swine, and human flu strains.
The team also simulated repeated viral transmissions to observe how the absence of IFITM3 impacted mutation rates. Results showed that viruses adapted more quickly and induced more severe inflammation in IFITM3-deficient mice.
“A virus from a different species adapts faster when IFITM3 is not present,” said Yount. “Our findings emphasize the protein’s broad importance in defending against zoonotic viruses.”
The study underscores that individuals with IFITM3 deficiencies should be considered a vulnerable group in pandemic preparedness plans. Co-authors of the study include researchers from Ohio State and St. Jude Children’s Research Hospital.