A multi-institutional study led by researchers at the Indian Institute of Science (IISc) has shown how the dengue virus has evolved over the past few decades in the Indian subcontinent. The work was recently published in PLoS Pathogens.
Although cases of dengue have steadily increased in the last 50 years, predominantly in South-East Asian countries, India has no approved vaccines against this mosquito-borne viral disease. Other countries, however, have developed some vaccines.
“We were trying to understand how different the Indian variants are, and we found that they are very different from the original strains used to develop the vaccines,” said IISc’s Rahul Roy, the corresponding author of the study. The researchers examined all available (408) genetic sequences of Indian dengue strains collected from infected patients between 1956 and 2018.
Using computational analysis, the team examined how much each of the four known serotypes of the virus (Dengue 1, 2, 3, and 4) deviated from their ancestral sequence, from each other, and from other global sequences. It was found that the sequences were changing in a very complex manner. The researchers found that until 2012, Dengue 1 and 3 were the dominant strains in India. But in recent years, Dengue 2 has become more dominant, while Dengue 4—once considered the least infectious—is now establishing itself in south India. According to Suraj Jagtap, the lead author, one possible factor could be antibody-dependent enhancement (ADE).
ADE occurs when people get infected first with one serotype and then develop a secondary infection with a different serotype with more severe symptoms. Scientists believe that if the second serotype is similar to the first, the antibodies generated after the first infection bind to the new serotype and to immune cells called macrophages. This results in the second serotype infecting 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 the dengue virus,” Jagtap said.
At any given time, 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 two to three years. Over time, the antibody levels decline, and cross-serotype protection is lost. The researchers propose that if a person gets infected by a similar, but not identical, viral strain around this time, then ADE kicks in, giving the new strain a huge advantage and causing it to become the dominant strain in the population. This advantage lasts for a few more years after which the antibody levels become too low to make a difference.
“Nobody has shown such interdependence between the dengue virus and the immunity of the human population before,” said Roy. Such insights are possible only from studying the disease in countries like India, said Roy, as the infection rates here are historically high and a large population carries antibodies from a previous infection.