Science and Nature

Host immunity drives viral evolution of dengue

This transmission electron minute (TEM) portray depicts a resolution of round, Dengue virus particles that have been printed in this tissue specimen. Credit: CDC/ Frederick Murphy

Fresh overview by a crew of College of Florida investigators, and others, provides proof that host immunity drives evolution of the dengue virus. The work, printed this day in Science, retrospectively analyzes two an extended time of dengue virus genetic variation from Thailand, alongside inhabitants-level measures of an infection and immunity.

There are four sorts of dengue virus, and all four have co-circulated in Thailand since the early 1960s. This provides a probability to peruse how the viruses compete towards one but any other for human hosts.

“We wanted to grasp the ecology and evolution of dengue viruses circulating in a single build over an extended timeframe,” says the peruse’s lead author, Leah Katzelnick, previously a submit-doc in biology at the College of Florida and now Chief of Viral Epidemiology and Immunity Unit at the Nationwide Institute of Hypersensitivity and Infectious Illnesses.

Dengue virus kinds are grouped in step with how their surface proteins, or antigens, work along with an infection-combating antibodies in human blood. The four kinds, also veritably known as serotypes, are successfully-known as DENV1 by diagram of DENV4. Though there’s genetic variation between each and each dengue virus kind, there’s also variation inner each and each dengue virus kind.

“We’re searching to grasp if or how immunity is driving extinction or persistence of particular lineages of dengue virus circulating in this one build. To affect that, we characterized the immune signature of dengue viruses isolated in Bangkok over an extended timeframe,” says Derek Cummings, the peruse’s senior author and a professor of biology at UF.

The unique peruse old 1,944 archival blood samples from Bangkok. The samples have been preserved from other folks known to be in heart-broken health with dengue and so that they signify all four dengue virus traces from every body year between 1994 and 2014. The crew genetically sequenced greater than 2,000 virus samples.

The researchers then performed checks on a smaller subset of samples that represented a time sequence of every and each tension. From this, they then characterized the antigenic relationship of the traces to at least one but any other by diagram of time. Antigenic relationships signify how successfully an immune response to at least one virus protects towards other viruses.

“We stumbled on that there is a sample love influenza, the build we salvage varied viruses every body year that are pushed by pure resolution for viruses that evade the human immune response to the inhabitants,” says Cummings, who’s also a college member of the UF Rising Pathogens Institute. “Now we have shown that that this is also occurring with dengue.”

Mapping antigenic switch

The crew old a direction of known as antigenic cartography which makes a draw to visualise the relatedness of viruses.

“When two viruses are shut on that draw, then which manner immune responses ‘sees’ the viruses as equivalent,” Katzelnick says. “As an illustration, for these that may well doubtless be infected with one virus, then an immune response to that virus would defend you towards but any other virus that’s inner attain on the draw.”

The crew stumbled on an total sample of dengue virus traces evolving far from one but any other over the 20-one year peruse timeframe. Whereas the serotypes now and then oscillated closer, in frequent they grew further apart.

However the outcomes also demonstrate a clear inverse relationship between the level of antigenic diversity in a given one year and epidemic stages. When Thailand experienced dapper epidemic outbreaks, antigenic diversity became once low. However in years when epidemic stages have been lower than moderate, the antigenic diversity became once larger.

“In frequent, it be been idea that for these that salvage infected with one serotype of DENV then you surely may well doubtless be immune to that serotype for the relaxation of your life,” Cummings says. “However there have been observations the build that looks to no longer be strictly stunning.”

One aim behind re-infections is that dengue viruses will be subject to pure selective forces to evade the immune blueprint of previously infected individuals. In essence, they have to switch barely ample to maintain far from immune detection in a bunch the build but any other serotype has already triggered an an infection.

“Our findings counsel that the dengue viruses are shifting far from the viruses that generated immunity in the inhabitants in the past,” says Henrik Salje, a co-author of the peruse and assistant professor at Cambridge College. “It is trend of love the flu memoir, dengue is evolving to race the immunity that’s in the inhabitants at any particular time. However it looks to be occurring at a slower tempo with dengue than influenza.”


Researchers already knew that there is a elaborate interplay between immunity and the dengue virus. When someone is uncovered to a serotype of this virus, they’re going to incessantly experience a steady an infection that ends in partial an infection. However when they are uncovered again, the partial immunity can trigger an overreaction that can lead to severe outcomes. The dengue virus looks, in these conditions, to no longer simplest evade the immune response, however reveal it to its advantage to doubtlessly lengthen its rate of direct.

“Ninety to 95% of the individuals displaying up at a health facility in Bangkok with dengue are having their 2d an infection,” Cummings says. “And the general public that are living their total lives in Bangkok are getting infected extra than one times.”

This enhanced an infection phenomenon may well simply also make a contribution to the evolution of the pathogen, deciding on for viruses that are equivalent ample to make basically the many of the immune response.

“General, viruses have been rising extra varied from one but any other over time, however we also noticed that they grew closer collectively in the direction of some durations of time, in particular early in the time sequence. This capability a tradeoff between evading immunity and making basically the most of partial immunity,” Katzelnick says.

Cummings says the unique work provides clues to the ecology of dengue and also is linked to vaccine invent and ongoing surveillance efforts.

“The implications are no longer no longer like we’re seeing in the COVID-19 epidemic, we have gotten to update viral surveillance to grasp a community’s immunity and what’s circulating,” Cummings explains. “This paper is suggesting that the dengue viruses are altering and we have gotten to update how we affect surveillance to larger understand immunity in populations and to in a roundabout diagram gash relief the resolution of different folks that salvage in heart-broken health.”

More recordsdata:
Leah Katzelnick et al, Antigenic evolution of dengue viruses over 20 years, Science (2021). DOI: 10.1126/science.abk0058.

Host immunity drives viral evolution of dengue (2021, November 18)
retrieved 18 November 2021

This doc is subject to copyright. Aside from any stunning dealing for the aim of personal peruse or overview, no
phase will be reproduced without the written permission. The direct material is offered for recordsdata applications simplest.

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