There are many processes and proteins that help the body fight a flu infection. One of them is known as IFITM3. Researchers have now shown that this protein can help prevent viruses from mutating after they have infected a new host. But some people are deficient in IFITM3, which can raise their risk of a severe flu infection. That deficiency is not unusual in some groups. For example, around twenty percent of Chinese people and four percent of people with European ancestry carry variants in IFITM3 that can interfere with the protein's expression. This study has shown that these genetic variants can allow flu viruses to establish infections even when the virus is present at very low levels that would not usually cause infection. The findings have been reported in Nature Communications.
The IFITM3 (interferon-induced transmembrane protein 3) protein is part of the innate immune system, and is generated at high levels after the detection of a flu infection. It can sequester viral particles so that they are not able to replicate, which reduces the severity of flu infections. Mouse models that are IFITM3 deficient are extremely vulnerable to the flu.
“An IFITM3 deficiency makes it easier for a low dose of virus to be infectious,” said senior study author Jacob Yount, a professor of microbial infection and immunity at Ohio State College of Medicine.
Right now, the H5N1 avian influenza is causing considerable losses of wild and agricultural birds around the world, which has been ongoing for several years. Many experts are concerned that this virus could threaten humans.
“It’s these emergent viruses that we’ve never encountered before where IFITM3 is really the most important,” Yount said. “Our study supports the idea that not only would you get a more severe infection, but you’re more likely to get infected in the first place and more likely to help the virus adapt if you are IFITM3 deficient.”
In this work, the researchers compared the pathogenicity of two avian flu strains, one of which was H5N1, in a mouse model of IFITM3 deficiency and in normal mice. Viral loads were detectable in all of the mice after they were exposed to either ten or fifty viral particles. But in mice that lacked IFITM3, only one viral particle was necessary to create infection and inflammation. Normal mice were unaffected and not infected by a single viral particle.
“IFITM3 has been known to prevent severity of infection, but we’re newly showing that it’s also controlling how much virus it takes initially to cause infection,” Yount said. “And I think that’s one of the most fundamental textbook-level findings ever to come out of my lab.”
Additional research confirmed that cell lines lacking IFITM3 were more likely to be infected many different strains of flu, including eleven avian, and three swine flu viruses.
The study authors noted that IFITM3 deficiency may be important to consider during pandemic preparation efforts.
Sources: Ohio State University, Nature Communications
