“This is a major accomplishment for an undergraduate,” said Holm.
The research was initiated by Amanda Anafu ’14, who was a summer research intern in 2011. Each summer, more than 150 undergraduates work in concert with faculty members on projects from many different disciplines. Students get one-on-one attention as they pursue research and scholarly projects that they initiate. This mentorship opportunity can sometimes lead to getting published in peer reviewed journals.
Anafu found that the presence of the protein IFITM3 in certain cells could decrease the capacity for reovirus, which is associated with various diseases in animals, including humans, to enter them. Together, Anafu and Holm found that IFITM3 likely acts in endosomes (vesicles that form within cells) to delay the entry process, which results in virus particles becoming degraded and therefore incapable of starting an infection.
“Amanda’s work is significant,” says Holm. “It is the first demonstration that IFITM3 can inhibit a non-enveloped virus – it could have implications for other human pathogens.”
The research was a collaboration with Abraham Brass of the University of Massachusetts Medical School. His group, which also studies IFITM3, had previously identified it as a factor that inhibits the entry of influenza virus into cells. Mutations in this protein are associated with increased severity of influenza infection in humans. IFITM3 is produced during the initial immune response, and functions in a cellular compartment called an endosome to prevent influenza virus particles from fusing their membranes, termed “envelopes,” with cellular membranes, to allow the viruses to get inside the cell.
In particular, Holm studies a non-enveloped virus, mammalian reovirus, which also needs to get into endosomes in order to enter a cell, although the mechanism of entry is quite different.
Chris Bowen, also listed on the paper, is a research technician, funded by an NIH R15 grant.