Host Immunity to Blame for Dengue Virus Evolution

New research by a team of University of Florida investigators, and others, provides evidence that host immunity drives evolution of the dengue virus. The work, published today in Science, retrospectively analyzes two decades of dengue virus genetic variation from Thailand, alongside population-level measures of infection and immunity.

“We want to understand if or how immunity is driving extinction or persistence of particular lineages of dengue virus circulating in this one place. To do that, we characterized the immune signature of dengue viruses isolated in Bangkok over a long period of time,” says Derek Cummings, the study’s senior author. The new study used 1,944 archival blood samples from Bangkok. The samples were preserved from people known to be ill with dengue and they represent all four dengue virus strains from every year between 1994 and 2014. The team genetically sequenced more than 2,000 virus samples.

The researchers then performed tests on a smaller subset of samples that represented a time series of each strain. From this, they then characterized the antigenic relationship of the strains to each other through time. “We found that there is a pattern like influenza, where we get different viruses every year that are driven by natural selection for viruses that evade the human immune response to the population,” says Cummings. “We have shown that this is also happening with dengue.” The team used antigenic cartography to visualize the relatedness of viruses.

The team found an overall pattern of dengue virus strains to evolve away from each other over the 20-year study timeframe. While the serotypes at times oscillated closer, in general, they grew further apart. “Our findings suggest that the dengue viruses are moving away from the viruses that generated immunity in the population in the past,” concluded Henrik Salje, a co-author of the study and assistant professor at Cambridge University. “It’s sort of like the flu story, dengue is evolving to escape the immunity that is in the population at any particular time. But it seems to be happening at a slower pace with dengue than influenza.”