IISc’s computational analysis by its research team shows how dengue virus evolved in India

The Indian Institute of Science (IISc) has embarked on a multi-institutional study on dengue to prove that the virus causing the disease has evolved dramatically in India. The research was done going by the rising cases of the mosquito-borne viral disease predominantly in the South-East Asia. There are no approved vaccines against dengue in India, although there are preventive shots in other countries.

The research was supported by a philanthropic grant from Narayana Murthy, co-founder and chairman emeritus of Infosys and funding from the Wellcome Trust-DBT India Alliance.

“We researched to understand how different the Indian variants are. We found a big difference from the original strains used to develop the vaccines,” said Rahul Roy, Associate Professor, Department of Chemical Engineering (CE), IISc, and corresponding author of the study published in PLoS Pathogens.

The researchers examined all available 408 genetic sequences of Indian dengue strains from infected patients collected between the years 1956 and 2018 by others as well as the team themselves.

There are four serotypes of the dengue virus: 1, 2, 3 and 4. Using computational analysis, the team examined how much each of these serotypes deviated from their ancestral sequence and from other global sequences. “The sequences are changing in a very complex manner,” he stated.

Until 2012, the dominant strains in India were Dengue 1 and 3. But in recent years, Dengue 2 has become more dominant, while Dengue 4 once considered the least infectious is now making a niche in South India. The team sought to investigate what factors decide which strain is the dominant one at any given time. One possible factor could be Antibody Dependent Enhancement (ADE), said Suraj Jagtap, PhD student, Department of Chemical Engineering and first author of the study.

Sometimes people might be infected first 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 bind to the new serotype and bind to immune cells called macrophages. This proximity allows the newcomer to infect macrophages, making the infection more severe. “We knew that ADE enhances severity, [but] we wanted to know if that can also change the evolution of dengue virus,” Jagtap adds.

Several strains of each serotype exist in the viral population. The antibodies generated in the human body after a primary infection provide complete protection from all serotypes for about 2-3 years. Over time, the antibody levels begin to drop, and cross-serotype protection is lost. The researchers proposed that if the body is infected around this time by a similar not identical viral strain, then ADE kicks in, giving a huge advantage to this new strain, 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, said Prof. Roy.

“Nobody has shown such interdependence between the dengue virus and the immunity of the human population before. This is probably why the recent Dengue 4 strains, which supplanted the Dengue 1 and 3 strains, were more similar to the latter than their own ancestral Dengue 4 strains, the researchers believe. Such insights are possible only from studying the disease in countries like India with genomic surveillance, because the infection rates here are high, and a huge population carries antibodies from a previous infection,” said Prof. Roy.

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