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Studies Trace Flu Virus Evolution and Dispersal

NEW YORK (GenomeWeb News) – Two new papers are providing insights into how seasonal influenza viruses evolve and spread.
In the first, published in today’s issue of Science, researchers from the University of Cambridge and the World Health Organization’s Global Influenza Surveillance Program used sequencing and a method called antigenic cartography to track the travels of influenza virus A H3N2, the most common flu virus. The researchers found that flu outbreaks follow a predictable path around the world starting in East and Southeast Asia.
“The ultimate goal of our collaboration is to increase our ability to predict the evolution of influenza viruses,” senior author Derek Smith, a virologist and computer scientist affiliated with the University of Cambridge and Erasmus Medical Center in the Netherlands, said in a statement. “This study is one step along that path and in particular highlights the importance of ongoing collaborations and surveillance in East and Southeast Asia, and expanding these collaborations in the future.”
Each year, somewhere between five and 15 percent of the world’s population becomes infected during influenza A epidemics. These flu outbreaks are linked to as many as a half a million deaths annually, according to WHO. While vaccinations can be effective, influenza viruses often evolve so rapidly that creating effective vaccines can be difficult.
WHO’s Global Influenza Surveillance Network — consisting of more than 100 labs in 80 countries — tracks influenza virus evolution in order to try to decide which strains should be used in seasonal vaccines. But the data can also contribute to a better understanding of influenza evolution and spread in general.
Smith and his team focused on one of eight regions of the flu genome, HA, which codes for a surface protein hemagglutinin targeted by the human immune system. They analyzed about 13,000 H3N2 samples collected on six continents between 2002 and 2007, sequencing the HA1 domain of roughly 1,500 of these. Together, antigenic mapping and phylogenic analyses allowed them to differentiate between flu strains and determine when each arrived at each location.
The results suggest that new strains usually begin in East and Southeast Asia, where they circulate continuously. These “seed” other outbreaks by proceeding first through Oceania, then Europe and North America, and eventually South America. But the paper indicates that viruses hardly ever go back in the other direction.
If this pattern holds, the authors suggested, it may give health officials a leg up on predicting the most dangerous strains each flu season, since they should be able to select vaccination strains for the next season based on surveillance of East and Southeast Asia. “Intensified surveillance, including whole-genome sequencing, and better understanding of the evolutionary pressures in E-SE Asia would further improve vaccine strain selection worldwide and potentially make influenza virus evolution more predictable,” they wrote.
Similarly, another paper, which appeared in the advance online edition of Nature this week, used comparative genomics to assess the evolutionary dynamics of H3N2 and another influenza A strain, H1N1. These researchers also suggest that influenza A strains in one region seed outbreaks in the rest of the world, following a “source-to-sink” pattern, though they didn’t implicate Asia — but rather tropics in general — as the source.
“The results suggest a sink-source model of viral ecology in which new lineages are seeded from a persistent influenza reservoir, which we hypothesize to be located in the tropics, to sink populations in temperate regions,” lead author Andrew Rambaut, an evolutionary biologist at the University of Edinburgh, and his colleagues wrote. “Although southern China has been proposed as the epicenter of influenza A virus, it is possible that tropical regions generally represent ideal source populations because of viral transmission.”
The team compared sequence data from the 1,302 complete viral genomes collected from populations in New York state and New Zealand over a dozen years as part of the Influenza Genome Sequencing Project. They analyzed data from all eight regions of the genome, comparing evolution between genome segments, viral subtypes, and locations to ascertain evolutionary dynamics for H3N2 and H1N1.
Their data also provides information about influenza evolution, suggesting influenza A evolves through both frequent re-assortment and so-called periodic selective sweeps. It also suggests that H3N2 and H1N1 had different evolutionary dynamics, with H1N1 greater genetic variation in a given flu season.
The researchers also found evolutionary differences within viral populations and between different regions of the genome. For instance, the authors noted, genes expressed on the virion surface — particularly HA — generally evolved more quickly than genes whose products have internal functions.
And, they reported, influenza A’s evolutionary dynamics are driven not by one, but many genetic changes through a “complex interplay between rapid mutation, frequent reassortment, widespread gene flow, natural selection (occasionally generating genome-wide selective sweeps), functional interactions among segments, and global epidemiological dynamics.”

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