Host immunity drives viral evolution of dengue

New analysis by a crew of University of Florida investigators, and others, supplies proof that host immunity drives evolution of the dengue virus. The work, revealed as we speak in Science, retrospectively analyzes twenty years of dengue virus genetic variation from Thailand, alongside population-level measures of an infection and immunity.

There are 4 varieties of dengue virus, and all 4 have co-circulated in Thailand for the reason that early Nineteen Sixties. This supplies a possibility to review how the viruses compete towards one another for human hosts.

“We wanted to understand the ecology and evolution of dengue viruses circulating in one place over a long period of time,” says the research’s lead creator, Leah Katzelnick, beforehand a post-doc in biology on the University of Florida and now Chief of Viral Epidemiology and Immunity Unit on the National Institute of Allergy and Infectious Diseases.

Dengue virus varieties are grouped in response to how their floor proteins, or antigens, work together with infection-fighting antibodies in human blood. The 4 varieties, additionally referred to as serotypes, are famous as DENV1 by means of DENV4. Although there’s genetic variation between every dengue virus kind, there’s additionally variation inside every dengue virus kind.

“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 research’s senior creator and a professor of biology at UF.

The new research used 1,944 archival blood samples from Bangkok. The samples have been preserved from folks recognized to be in poor health with dengue and so they characterize all 4 dengue virus strains from yearly between 1994 and 2014. The crew genetically sequenced greater than 2,000 virus samples.

The researchers then carried out exams on a smaller subset of samples that represented a time collection of every pressure. From this, they then characterised the antigenic relationship of the strains to one another by means of time. Antigenic relationships characterize how nicely an immune response to 1 virus protects towards different viruses.

“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, who can also be a school member of the UF Emerging Pathogens Institute. “We have shown that that this is also happening with dengue.”

Mapping antigenic change

The crew used a course of referred to as antigenic cartography which makes a map to visualise the relatedness of viruses.

“When two viruses are close on that map, then that means immune responses ‘sees’ the viruses as similar,” Katzelnick says. “For example, if you are infected with one virus, then an immune response to that virus would protect you against another virus that is nearby on the map.”

The crew discovered an general sample of dengue virus strains evolving away from one another over the 20-year research timeframe. While the serotypes at occasions oscillated nearer, basically they grew additional aside.

But the outcomes additionally present a transparent inverse relationship between the extent of antigenic range in a given yr and epidemic ranges. When Thailand skilled giant epidemic outbreaks, antigenic range was low. But in years when epidemic ranges have been decrease than common, the antigenic range was increased.

“In general, it’s been thought that if you get infected with one serotype of DENV then you are immune to that serotype for the rest of your life,” Cummings says. “But there have been observations where that seems to not be strictly true.”

One clarification for re-infections is that dengue viruses could also be topic to pure selective forces to evade the immune system of beforehand contaminated people. In essence, they need to change simply sufficient to keep away from immune detection in a number the place one other serotype has already brought about an an infection.

“Our findings suggest that the dengue viruses are moving away from the viruses that generated immunity in the population in the past,” says Henrik Salje, a co-author of the research 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.”

Implications

Researchers already knew that there’s a complicated interaction between immunity and the dengue virus. When somebody is uncovered to a serotype of this virus, they are going to sometimes expertise a light an infection that leads to partial an infection. But when they’re uncovered once more, the partial immunity can set off an overreaction that may result in severe outcomes. The dengue virus seems, in these circumstances, to not solely evade the immune response, however use it to its benefit to probably improve its charge of development.

“Ninety to 95% of the people showing up at a hospital in Bangkok with dengue are having their second infection,” Cummings says. “And most people who live their whole lives in Bangkok are getting infected multiple times.”

This enhanced an infection phenomenon may contribute to the evolution of the pathogen, choosing for viruses which can be comparable sufficient to benefit from the immune response.

“Overall, viruses were growing more different from each other over time, but we also observed that they grew closer together during some periods of time, particularly early in the time series. This indicates a tradeoff between evading immunity and taking advantage of partial immunity,” Katzelnick says.

Cummings says the brand new work provides clues to the ecology of dengue and in addition is related to vaccine design and ongoing surveillance efforts.

“The implications are not unlike we are seeing in the COVID-19 epidemic, we need to update viral surveillance to understand a community’s immunity and what is circulating,” Cummings explains. “This paper is suggesting that the dengue viruses are changing and we need to update how we do surveillance to better understand immunity in populations and to ultimately reduce the number of people who get sick.”