The study, "Networks link antigenic andreceptor-bindingsites of influenza hemagglutinin: Mechanistic insight into fitter strainpropagation," was published Dec. 19 in the online edition of Scientific Reports, an open-accessjournal published by Nature. In it,the researchers observed a flu virus passing through pre-vaccinated mice andobserved that emergent antigenic site mutations on the viral protein hemagglutinin(HA) impacted host receptor-binding affinity—and therefore, the evolution offitter influenza strains.
Flu shots are reformulated every year as new flu strainsemerge, but vaccines can also stimulate production of antibodies that target asection of the HA protein called the antigenic site. In 2009, MIT researcherRam Sasisekharan and scientists at the National Institute of Allergy andInfectious Diseases (NIAID) reported that when a virus encounters suchantibodies, it can evolve into a slightly altered strain that can spread topeople who have not been vaccinated.
To further understand this phenomenon, Sasisekharan and hiscolleagues analyzed the network of amino acids that make up HA and identifiedwhich amino acids are most likely to undergo mutations that improve theviruses' ability to infect new hosts. The researchers then computed theSignificant Interactions Network (SIN) for each residue of HA and mapped the networksof antigenic site residues on the HA of influenza A virus subtype H1N1.
"Specific antigenic site residues are 'linked' to RBSresidues via their SIN and mutations within 'RBS-linked' antigenic residues cansignificantly influence receptor-binding affinity by impacting the SIN of keyRBS residues," the researchers concluded. "In contrast, other antigenic siteresidues do not have such 'RBS-links' and do not impact
receptor-binding affinity upon mutation."
According to Sasisekharan, the finding could help fluvaccine designers produce vaccines that do not induce the evolution of fitterviruses.
"This understanding of the relationship between theantigenic site and the receptor-binding site could be added to the currentmethods of vaccine selection and vaccine designs to limit drift," he told MIT'spress office. Sasisekharan is an Edward Hood Taplin Professor of HealthSciences and Technology and Biological Engineering at MIT, director of theHarvard-MIT Division of Health Sciences and Technology and senior author of thepaper.
Continued analysis of circulating influenza HA sequences canpotentially accelerate and help in the design of ideal vaccines for each fluseason, according to MIT.
The study was supported by funding from the U.S. National Institutesof Health and the Singapore-MIT Alliance for Research and Technology.
