Highlights

Above

The molecular structure of hemagglutinin, a surface protein of the influenza virus. Positions in the protein that help the virus better adapt to a new cellular environment are colored.

© 2019 A*STAR Bioinformatics Institute

How the flu virus hops from one host to another

29 Nov 2019

A*STAR researchers have identified specific sites in the surface protein of influenza viruses that allow the pathogen to adapt to different host organisms.

From birds to cats, pigs to humans, many animals fall ill with their own variant of the flu virus, also known as the influenza virus. But every once in a while, an influenza variant manages to cross the species divide. For example, the virus strain responsible for the 1997 outbreak of avian influenza in Hong Kong was detected in humans—the strain had essentially adapted to a new host organism.

To understand how host adaptation occurs, Sebastian Maurer-Stroh and colleagues at the Bioinformatics Institute (BII), A*STAR, with collaborators in Singapore, the Netherlands and the US, are diving deep into the protein sequences of influenza viruses. Of particular interest to them is the hemagglutinin protein of influenza viruses, which plays a crucial role in infection. What they seek to pinpoint are passage bias sites—positions in the hemagglutinin protein that help the influenza virus better adapt to a new cellular environment.

Analyzing more than 80,000 influenza hemagglutinin sequences where information on passage in cells of different species was available, the researchers identified 54 common passage bias sites in the hemagglutinin of influenza variants.

“These 54 sites lie in three structural regions of the hemagglutinin protein: the receptor-binding site which enables the virus to enter the host cell, the region that affects the pH-dependent structural changes of the protein, and the N-terminal signal peptide of the protein,” Maurer-Stroh said. Of the three, the impact of N-terminal signal peptide mutations is the least well understood in the context of host adaptation, he added.

The research group also demonstrated that some passage bias sites in the hemagglutinin proteins show signs of epistasis, which means that these adaptation mutations do not appear independently. Hence, the sum of all mutations is likely to determine productive adaptation. These findings indicate that it is difficult to generalize transmissibility behavior of a virus based on previous experiments that do not consider the effects of multi-variant interactions.

“Our data will be valuable to researchers who track emerging influenza viruses that have the potential to cause local epidemics or global pandemics using our tool FluSurver,” said Maurer-Stroh.

In addition, because influenza vaccines are produced by growing human viruses in egg cells, those viruses typically undergo mutations that adapt them to better growth in chickens rather than in humans. Maurer-Stroh is working on another project with colleagues at the Genome Institute of Singapore (GIS), A*STAR, to understand how this can sometimes affect the efficacy of the vaccine.

“We will further examine the role of the understudied signal peptide region of hemagglutinin in host adaptation. We also plan to identify cell passage adaptive sites for other viral proteins and continue our work on the interplay between egg adaptation and vaccine efficacy,” he said.

The A*STAR-affiliated researchers contributing to this research are from the Bioinformatics Institute (BII).

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References

Lee, R. T. C., Chang, H. H., Russell, C. A., Lipsitch, M. and Maurer-Stroh, S. Influenza A Hemagglutinin Passage Bias Sites and Host Specificity Mutations. Cells 8(9), 958 (2019) | article

About the Researcher

Sebastian Maurer-Stroh

Deputy Executive Director (Research)

Bioinformatics Institute
Sebastian Maurer-Stroh obtained his PhD degree from the University of Vienna, Austria, before carrying out research at the VIB Switch laboratory in Brussels, Belgium, under a Marie Curie fellowship. He joined A*STAR’s Bioinformatics Institute (BII) in 2007 and now leads a group of experts in protein sequence analysis as a Senior Principal Investigator. He was appointed Deputy Executive Director (Research) at BII in 2019. Maurer-Stroh also spearheads industry collaborations with local SMEs and large multinationals on sequence analysis and prediction of allergenicity potential of proteins.

This article was made for A*STAR Research by Wildtype Media Group