New proof that host immunity drives evolution of the dengue virus

New analysis by a staff of College of Florida investigators, and others, offers proof that host immunity drives evolution of the dengue virus. The work, printed at present in Science, retrospectively analyzes 20 years of dengue virus genetic variation from Thailand, alongside population-level measures of an infection and immunity.

There are 4 forms of dengue virus, and all 4 have co-circulated in Thailand because the early Sixties. This offers a chance to check how the viruses compete towards one another for human hosts.

“We wished to grasp the ecology and evolution of dengue viruses circulating in a single place over an extended time period,” says the examine’s lead writer, Leah Katzelnick, beforehand a post-doc in biology on the College of Florida and now Chief of Viral Epidemiology and Immunity Unit on the Nationwide Institute of Allergy and Infectious Ailments.

Dengue virus varieties are grouped in accordance with 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 via DENV4. Though there’s genetic variation between every dengue virus sort, there’s additionally variation inside every dengue virus sort.

We wish to perceive if or how immunity is driving extinction or persistence of specific lineages of dengue virus circulating on this one place. To do this, we characterised the immune signature of dengue viruses remoted in Bangkok over an extended time period.”


Derek Cummings, examine’s senior writer and a professor of biology at UF

The brand new examine used 1,944 archival blood samples from Bangkok. The samples had been preserved from folks recognized to be sick with dengue they usually signify all 4 dengue virus strains from yearly between 1994 and 2014. The staff genetically sequenced greater than 2,000 virus samples.

The researchers then carried out checks 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 via time. Antigenic relationships characterize how properly an immune response to 1 virus protects towards different viruses.

“We discovered that there’s a sample like influenza, the place we get totally different viruses yearly which can be pushed by pure choice for viruses that evade the human immune response to the inhabitants,” says Cummings, who can also be a school member of the UF Rising Pathogens Institute. “We’ve proven that that that is additionally taking place with dengue.”

Mapping antigenic change

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

“When two viruses are shut on that map, then which means immune responses ‘sees’ the viruses as related,” Katzelnick says. “For instance, in case you are contaminated with one virus, then an immune response to that virus would defend you towards one other virus that’s close by on the map.”

The staff discovered an total sample of dengue virus strains evolving away from one another over the 20-year examine timeframe. Whereas the serotypes at occasions oscillated nearer, generally they grew additional aside.

However the outcomes additionally present a transparent inverse relationship between the extent of antigenic variety in a given yr and epidemic ranges. When Thailand skilled massive epidemic outbreaks, antigenic variety was low. However in years when epidemic ranges had been decrease than common, the antigenic variety was greater.

“Normally, it has been thought that in case you get contaminated with one serotype of DENV then you might be resistant to that serotype for the remainder of your life,” Cummings says. “However there have been observations the place that appears to not be strictly true.”

One rationalization 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 bunch the place one other serotype has already brought on an an infection.

“Our findings counsel that the dengue viruses are transferring away from the viruses that generated immunity within the inhabitants up to now,” says Henrik Salje, a co-author of the examine and assistant professor at Cambridge College. “It is form of just like the flu story, dengue is evolving to flee the immunity that’s within the inhabitants at any specific time. However it appears to be taking place at a slower tempo 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 may usually expertise a gentle an infection that leads to partial an infection. However 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 enhance its fee of progress.

“Ninety to 95% of the folks displaying up at a hospital in Bangkok with dengue are having their second an infection,” Cummings says. “And most of the people who reside their complete lives in Bangkok are getting contaminated a number of occasions.”

This enhanced an infection phenomenon can also contribute to the evolution of the pathogen, deciding on for viruses which can be related sufficient to reap the benefits of the immune response.

“General, viruses had been rising extra totally different from one another over time, however we additionally noticed that they grew nearer collectively throughout some intervals of time, significantly early within the time collection. This means a tradeoff between evading immunity and making the most 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 should not not like we’re seeing within the COVID-19 epidemic, we have to replace viral surveillance to grasp a neighborhood’s immunity and what’s circulating,” Cummings explains. “This paper is suggesting that the dengue viruses are altering and we have to replace how we do surveillance to raised perceive immunity in populations and to finally scale back the quantity of people that get sick.”

Supply:

Journal reference:

Katzelnick, L.C., et al. (2021) Antigenic evolution of dengue viruses over 20 years. Science. doi.org/10.1126/science.abk0058.

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