A number of round, Dengue virus particles were revealed in this tissue specimen. CDC/ Frederick Murphy
The University of Florida has a team of investigators who have recently published new research that shows host immunity drives the evolution of the dengue virus. The work, published today in Science, analyzes two decades of genetic variation from Thailand, along with population-level measures of infection and immunity.
The four types of dengue virus have co-circulated in Thailand since the early 1960s. The opportunity to study how the viruses compete against each other is provided by this.
"We wanted to understand the ecology and evolution of the viruses in one place over a long period of time," says the study's lead author, who is now the Chief of Viral Epidemiology and Immunity Unit at the University of Florida.
There are different types of Dengue virus that interact with human blood. The four types are called DENV1 through DENV4. There is genetic variation between the different types of the virus.
We want to understand if immunity is driving extinction or persistence of particular lineages of the dengue virus in this one place. The senior author of the study, a professor of biology at the University of Florida, says that they characterized the immune signature of the viruses in Thailand.
The new study used a lot of blood samples. The samples were preserved from people who were known to be ill with the disease. More than 2,000 virus samples were genetically mapped by the team.
The researchers performed tests on a small subset of samples that represented a time series of each strain. They characterized the antigenic relationship of the strains through time. The immune response to one virus protects against other viruses.
"We found that there is a pattern 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 is also a faculty member of the UF Emerging Pathogens Institute. We have shown that this is happening with other diseases.
Antigenic change is mapped.
The team used a process called antigenic cartography to make a map.
The immune responses of the two viruses are similar. If you have a single virus, your immune response will protect you against another virus that is on the map.
The team found a pattern of strains evolving away from each other. The different types grew further apart.
The results show a correlation between the level of antigenic diversity and epidemic levels. Antigenic diversity was low when Thailand experienced large epidemics. The antigenic diversity was higher when epidemic levels were lower.
If you get a single type of DENV, then you are immune to that type for the rest of your life, according to Cummings. There have been observations where that is not true.
One explanation for re-infections is that the viruses may be able to evade the immune system of people who have previously been exposed. They have to change just enough to avoid immune detection in a host where a different type of vaccine has already been used.
The findings suggest that the viruses that caused the population to be immune in the past are no longer present. "It's like the flu story, the population's immunity is changing to escape the disease." It seems to be happening at a slower pace with the mosquito-borne disease.
Implications
There is a complex interplay between immunity and the virus. When someone is exposed to this virus, they will usually experience a mild infection. The partial immunity can cause an overreaction that can lead to serious outcomes. In these cases, the dengue virus appears to be able to evade the immune response and use it to increase its rate of growth.
Most of the people who show up at a hospital in Thailand with a disease are having a second one. Most people who live their entire lives in Bangkok are getting infections multiple times.
The evolution of the pathogen may be influenced by the enhanced infection phenomenon and the selection of viruses that are similar enough to take advantage of the immune response.
Over time, viruses were growing different from each other, but we also observed that they grew closer together during some periods of time, particularly early in the time series. This shows a tradeoff between taking advantage of partial immunity and evading it.
The new work gives clues to the ecology of the disease and is relevant to vaccine design.
The implications are similar to the COVID-19 epidemic, we need to update viral surveillance to understand a community's immunity and what is circulating. The paper suggests that we need to update how we watch for the disease to better understand immunity in populations and to reduce the number of people who get sick.
The antigenic evolution of the viruses over the last 20 years is described in the paper. www.science.org/doi/10.1126/science.abk0058
Science journal information.
Host immunity drives the evolution of a disease.
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