Keio Research Highlights

Two new detection methods for the influenza virus could help prevent the next global pandemic.

Seasonal influenza is responsible for up to 500,000 deaths around the world every year, and pandemic strains of the virus have periodically killed many more. Current methods to diagnose and track flu outbreaks are cumbersome, expensive or both.

A simpler technique for identifying patients in the early stages of infection could help get anti-influenza therapies faster to those who need them, and so limit the infection of others.

A team led by Toshinori Sato from Keio University's Department of Biosciences and Informatics exploited the fact that influenza invades the human respiratory tract and bloodstream by focusing on a sugar molecule found on the surface of our cells called sialic acid. Through a special kind of binding between sialic acid and a flu protein called hemagglutinin, viral particles can enter the human body, replicate and make us sick.

Sato and his colleagues previously identified a short chain of amino acids that mimics sialic acid, which they used as a decoy to bind viral hemagglutinin and prevent cell infection in the lab. Now, they have taken the same short peptide chain and developed two diagnostic assays for revealing the presence of influenza in a throat swab or other form of patient sample.

For the first test¹, Sato's team created a membrane that combined the peptide with a fatty molecule called a phospholipid. This preparation was fixed to a surface where it selectively attached to hemagglutinin when incubated with a flu-containing sample. Once all the flu particles had been collected, the researchers could then count them using traditional chemical and genetic techniques.

The other test² also started with the sialic-acid-mimic peptide, but in this case the researchers attached it to a highly sensitive electrode made of a diamond enhanced with the mineral boron. Any time a flu particle attached to the peptide, Sato and his colleagues could then detect its presence though electrochemical changes in the diamond sensor, without the need for additional assays.

By avoiding the use of complex biological molecules, Sato says that his peptide-based diagnostics offer several advantages over existing ones in terms of manufacturing, storage and engineering. But perhaps the biggest benefit comes from the peptides mimicking a part of the flu virus essential for its survival. So, whereas other tests need to be designed anew whenever a novel flu strain arises, according to Sato, "we expect that our strategy will be applicable to the detection of new influenza viruses that will appear in the near future."

1. Matsubara, T., Shibata, R. & Sato, T. Binding of hemagglutinin and influenza virus to a peptide-conjugated lipid membrane. Frontiers in Microbiology 7, 468 (2016). | article
2. Matsubara, T., Ujie, M., Yamamoto, T., Akahori, M., Einaga, Y. & Sato, T. Highly sensitive detection of influenza virus by boron-doped diamond electrode terminated with sialic acid-mimic peptide. Proceedings of the National Academy of Sciences USA 113, 8981-8984 (2016). | article