AsianScientist (Jun. 07, 2023) –Dengue is an epidemic in India with over 200,000 cases in 2022 alone, according to the government figures. While more than half of the population has some immunity against the dengue virus, it is specific to the strain they were infected with. This leads to regional spikes in dengue cases every few years as other strains become more prevalent.
A phenomenon that complicates the evolution of the dengue virus is the fact that a second infection with a different strain causes even more severe disease. Dubbed antibody-mediated enhancement, this complicates the task of developing a vaccine as the vaccine itself could act as the more severe, second infection in a population with a high prevalence of the virus. This is what happened in 2017 in the Philippines when schoolchildren were vaccinated with a dengue vaccine. Many children who had no prior infection, developed severe disease after getting the vaccine, with many succumbing to it.
For both limiting the spread of the virus and developing a vaccine against it, it is critical to know how the different dengue strains are evolving in a population. In the Indian population, all four strains of the dengue virus (DENV-1, -2, -3, -4) are in circulation. In a research published in the journal PLOS Pathogens, scientists from multiple institutes in Bangalore looked at their evolution.
Speaking to the Asian Scientist Magazine, Suraj Jagtap, the lead author and a graduate student at the Indian Institute of Science, said that dengue evolution is complex and little understood. The team was surprised to see a dengue strain becoming similar to other strains, something that has not been seen often in other viruses. “Before 2016, DENV-4 was different from DENV-1, DENV-2, and DENV-3. And after the 2016 outbreak, DENV-4 sequences are closer to DENV-1, DENV-2, and DENV-3,” Jagtap said.
For this study, the researchers looked at dengue gene sequences collected between 1956 and 2018 in the country. A bulk of these came from the authors’ previous work on sequencing dengue virus genomes since 2012. The team found that all four strains were simultaneously present in the population since 2000.
The researchers also found evidence that for any given region, subsequent spikes are of a different strain. The 2006, 2010, and 2013 spikes in dengue cases in Delhi were dominated by DENV-3, DENV-1, and DENV-2, respectively. While DENV-2 dominates in the rest of the country, DENV-4 has become the dominant strain in south India in recent years.
The fact that all four strains are circulating in a population where a significant proportion of the people have antibodies from previous infections impacts how the virus evolves. To probe the evolutionary dynamics, the researchers looked at how the E gene that codes for the dengue virus envelope protein is mutating over time.
The envelope mediates the virus’ ability to infect human cells and as it evolves, the antibodies against it from previous infections confer lesser protection. The researchers noted that the gene is mutating away from ancestral sequences in all strains, which means that it is evolving under selection pressure from the immunity present in the population.
Currently, there are several dengue vaccines in development, both in India and elsewhere. However, the researchers noted, that the dengue strains in India are evolving to diverge from the strains used for developing these vaccines. This demonstrates the need to factor in virus evolution in vaccine development for endemic diseases.
While tackling dengue is a global effort, there is no single-shot solution. Scientists need to sample the complete diversity of different genotype strains and lineages, and how they are evolving in different populations.
“Dengue variants that we see across the world are not the same, they are highly localized to the continent. So, what we suggest is that the vaccines should be designed locally, not globally,” Jagtap emphasized.
Source: Indian Institute of Science ; Image: Shutterstock
The paper can be found at: Evolutionary dynamics of dengue virus in India | PLOS Pathogens
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