New Delhi: A multi-institutional dengue study led by investigators from the Indian Institute of Science (IISc) shows how the disease-causing virus has evolved dramatically over the past few decades on the Indian subcontinent.
Cases of dengue, a mosquito-borne viral disease, have increased steadily over the past 50 years, predominantly in Southeast Asian countries. And yet, there are no approved dengue vaccines in India, although some vaccines have been developed in other countries, the IISc said in a press release.
“We were trying to understand how different the Indian variants are and found that they are very different from the parent strains used to develop the vaccines,” said Rahul Roy, Associate Professor, Department of Chemical Engineering (CE), IISc, and corresponding author of the paper. study published in PLoS Pathogens. He and his collaborators examined all available genetic sequences (408) of Indian dengue strains from infected patients collected between the years 1956 and 2018 by others, as well as by the team themselves.
There are four broad categories (serotypes) of dengue virus (Dengue 1, 2, 3 and 4). Wearing computational analysis, the team examined how much each of these serotypes deviated from their ancestral sequence, from each other, and from other global sequences. “We found that the sequences are changing in a very complex way,” Roy said.
Until 2012, the dominant strains in India were dengue 1 and 3. But in recent years, dengue 2 has become more dominant across the country, while dengue 4, once considered the least infectious , is now carving a niche for itself in South India. the researchers found. The team sought to investigate what factors decide which strain is dominant at any given time. One possible factor could be antibody-dependent enhancement (ADE), he said. Suraj Jagtap, a chemical engineering doctoral student and first author of the study.
Jagtap explained that sometimes people can first become infected with one serotype and then develop a secondary infection with a different serotype, leading to more severe symptoms. Scientists believe that if the second serotype is similar to the first, the antibodies in the host’s blood generated after the first infection binds to the new serotype and binds to immune cells called macrophages. This proximity allows the newcomer to infect macrophages, making the infection more serious. “We knew that ADE improves gravity, [but] we wanted to know if that can also change the evolution of dengue virusJagtap added. At any given time, there are several strains of each serotype in the viral population. He antibodies generated in the human body after a primary infection provide complete protection against all serotypes for approximately 2-3 years. Over time, antibody levels begin to decline and protection against cross-serotypes is lost. The researchers propose that if the body is currently infected with a similar, not identical, viral strain, then ADE is activated, giving this new strain a great advantage, causing it to become the dominant strain in the population. Such an advantage lasts for a few more years, after which the antibody levels become too low to make a difference. “This is what’s new in this article,” says Roy. “No one has ever demonstrated such an interdependence between the dengue virus and human population immunity before.” This is likely why recent Dengue 4 strains, which supplanted Dengue 1 and 3 strains, were more similar to the latter than their own ancestral Dengue 4 strains, the researchers believe.
Such insights are only possible by studying the disease in countries like India with genomic surveillance, Roy explained, because infection rates here have been historically high and a large population carries antibodies from a previous infection.
