Based on an evaluation of 184 whole-genome dengue sequences and 408 E gene sequences from India spanning greater than 60 years, a workforce led by Dr. Rahul Roy from the Department of Chemical Engineering on the IISc have carried out an in depth investigation of the virus variety and evolutionary dynamics of the virus in India. They have analysed how the virus evolves from its ancestors in the presence of serotypes.
Cross-protection
While the primary an infection with any of the 4 dengue serotypes can forestall reinfection by the identical serotype for an extended interval, the second an infection by a special serotype can have very excessive viral load and trigger extreme illness. This is as a result of the cross-protection provided by the primary an infection acts as a protect in opposition to different serotypes just for two-three years after which begins to drop.
Around one-three years after the cross-protection begins to wane is the time when antibody-dependent enhancement is most definitely. This is as a result of whereas the antibodies usually are not capable of neutralise the virus belonging to completely different serotypes, the virus is healthier capable of bind to the antibodies resulting in larger cell an infection and thus enhanced severity and viral load. This is named the antibody-dependent enhancement mediated by cross-reactive antibodies.
While the virus that’s equivalent to the one which induced the primary an infection might be neutralised for a very long time, viruses which can be a bit look-alike of the serotype that induced the primary an infection have larger skill to reap the benefits of the weakened immune responses and bind to pre-existing antibodies and trigger extreme illness than the three different serotypes that didn’t trigger the primary an infection, in keeping with Suraj Jagtap from the Department of Chemical Engineering, IISc and the primary writer of a paper printed in PLOS Pathogens.
“Several lines of evidence point to this interlinked dengue evolution driven by the underlying population-level natural immunity in India. The cross-reactive antibodies and cellular immunity from prior dengue infections can drive such co-evolution in endemic regions,” Dr. Roy elaborates.
The dominant immune choice stress has led to the emergence of a singular Indian dengue lineage (DENV-4-Id) belonging to serotype 4 (DENV-4). “The DENV-4-Id lineage has diverged away from global sequences,” says Dr. Roy.
South India
“The DENV-4-Id lineage is dominant in South India, and about 50% of infections in South India are due to this India-unique lineage,” says Dr. Roy. “We strongly feel that the DENV-4-Id lineage will become dominant in North India too.”
The E gene, which is seen throughout the dengue virus exterior, performs an vital position in binding to the cell receptors. The substitution price for the E gene was highest at 44% in genotype I of DENV-4 in contrast with the entire genome, suggesting excessive immunological stress driving the divergence of the DENV-4 E gene. “Most of dengue virus evolution happens in the E gene. This suggests that evolution is driven primarily due to interaction with host immune system,” says Dr. Roy.
Taking a cue from the divergence of DENV-4-Id, the researchers examined whether or not the excessive seroprevalence can play a task in the evolution of dengue in India. “We identified recurring fluctuations in the divergence of envelope gene sequences of circulating dengue viruses in South India, indicating that all four serotypes are co-evolving,” says Dr. Roy.
“In South India, we find that, in general, the E gene diverges from the ancestral sequence for all serotypes, but this divergence fluctuates over time. Overall, in our dataset, the E gene sequences within a serotype and between serotypes bring the viruses closer or similar to the ancestors or drift away from the ancestors. And this happens in a coordinated fashion across all four serotypes,” says Dr. Roy. “This behaviour is pronounced in DENV-2 and DENV-4 with an estimated time period (peak-to-peak) of about three years.”
The evolution of the viruses throughout serotypes has implications in vaccine efficacy. The majority of strains used for creating dengue vaccines are based mostly on strains remoted between 1964 and 1988.
“As the current Indian lineages are highly divergent from those used in all major vaccines (the genotypes used in the vaccine strains are not observed in India), there is a potentially significant reduction in vaccine efficacy,” says Dr. Roy. “Overall, about 6% of all known epitopic regions are different in Indian dengue sequences compared to the vaccine strains. Further, almost half of all the E protein variations lie either in known epitopic regions where the antibodies bind to or have a positive antigenic effect.”
Indian variants of DENV-1 and DENV-4 are distinct from all of the vaccines in comparison with DENV-2 and DENV-3.
