Research published today in the journal Nature has revealed unexpected differences in the way different flu viruses spread across the world.

Viruses that evolve more quickly circulate more quickly, but die out between epidemics. Those that evolve more slowly travel more slowly, but can circulate continuously between epidemics, enabling them to become more diverse.  

There are four types of influenza viruses that cause seasonal flu in humans: two influenza A viruses (H3N2 and H1N1) and two influenza B viruses (Yamagata and Victoria). While H3N2 viruses are the most common of the seasonal influenza viruses, H1N1 and B viruses also cause epidemics worldwide each year. The WHO selects representative strains of all four A and B viruses for inclusion in the seasonal influenza vaccine each year.

Importantly, all four of the viruses cause indistinguishable symptoms and evolve by similar mechanisms to escape immunity induced by prior infections and vaccinations. This evolution is part of why people get influenza multiple times over the course of their lives.

Previous research has shown that H3N2 viruses circulate continuously in east and southeast Asia throughout the year, spreading to the rest of the world each year to cause seasonal flu epidemics. Given the fundamental similarities between H3N2, H1N1, and B infection, it was thought that they would also emerge from east and southeast Asia to cause yearly epidemics worldwide. However, the work published today in Nature shows that in fact, H1N1 and B viruses behave very differently from H3N2 viruses.

The research was led by the University of Cambridge and the Fred Hutchinson Cancer Research Center, and involved all five World Health Organization (WHO) Influenza Collaborating Centres.

Senior author Dr Colin Russell, from the Department of Veterinary Medicine at the University of Cambridge, UK, said: “While H3N2 viruses die out between epidemics and new viruses emerge from east and southeast Asia every year, H1N1 and B viruses frequently circulate continuously between epidemics worldwide. This continuous circulation gives rise to a huge diversity in H1N1 and B viruses circulating globally.”

Co-author Dr Steven Riley, from the MRC Centre for Outbreak Analysis and Modelling at Imperial College London, said: “This wasn’t what we thought we'd find. Before we did the study, there was no reason to expect regional or national strains of influenza circulating in isolation for a number of years.”

The study found that the rate of global movement of each virus, and its ability to circulate continuously between epidemics, is shaped by how quickly that virus changes its coat to escape immunity in the human population. Viruses that evolve quickly, in particular H3N2, spread around the world rapidly, but die out quickly between epidemics. Viruses that evolve more slowly, like H1N1 and B viruses, spread around the world more slowly but are also better at circulating continuously between epidemics.

The differences in global movement patterns are related to who is getting infected: faster evolving viruses, like H3N2, can infect adults, who tend to travel more frequently than children, providing more opportunities for the virus to spread. Conversely, more slowly evolving viruses, such as H1N1 and B viruses, primarily infect children. Children get sick with all four seasonal flu viruses, but H3N2 evolves faster so it infects adults more often. This leads to a greater proportion of adult infections with H3N2 relative to H1N1 and B viruses, and faster spread of H3N2 viruses.

“Ultimately, this means that we can look at the viruses circulating in Asia to get a good idea of which H3N2 virus might spread worldwide, but for H1N1 and B it’s tremendously variable and the dominant variant can vary from one region of the world to another,” said Dr Russell.

The research was primarily funded by the Royal Society and US National Institutes of Health with extensive involvement of the World Health Organization’s Global Influenza Surveillance and Response System. The Imperial group were also supported by the Wellcome Trust, the Medical Research Council, and the NIHR Health Protection Research Unit in Modelling Methodology.

Reference

Bedford, T et al. Global circulation patterns of seasonal influenza viruses vary with antigenic drift. Nature; 8 June 2015.