Evolutionary dynamics of dengue virus in India

Area of Science:

• Virology
• Evolutionary Biology
• Epidemiology

Background:

• Dengue virus (DENV) causes significant public health burden in India, with over 100,000 cases annually.
• DENV evolves and adapts, leading to new variants, yet systematic evolutionary analysis in India is lacking.
• India's population has high prevalence of DENV-specific antibodies, influencing viral evolution.

Purpose of the Study:

• To conduct a comprehensive analysis of DENV evolution in India from 1956-2018.
• To examine spatio-temporal dynamics, genotype prevalence, and evolutionary relationships of Indian DENV strains.
• To investigate interserotype dynamics and divergence from vaccine strains.

Main Methods:

• Analysis of all available DENV gene sequences from India (1956-2018).
• Examination of spatio-temporal distribution and evolutionary relationships of DENV genotypes.
• Investigation of substitution rates, immune selection pressures, and divergence from vaccine strains.

Main Results:

• All DENV serotypes co-circulate in India with 3-4 year outbreak cycles.
• Dominant genotypes identified since 2000: DENV-1 (III), DENV-2 (cosmopolitan), DENV-3 (III), and DENV-4 (I).
• Envelope (E) protein shows immune selection signatures, with a highly divergent DENV-4-Id lineage in South India exhibiting significant antigenic site mutations.

Conclusions:

• DENV evolution in India is complex, driven by immunity and leading to divergence from vaccine strains.
• Recurring interserotype drift suggests selection via cross-reactive antibody-dependent enhancement.
• The emergence of divergent lineages like DENV-4-Id highlights the dynamic evolutionary landscape of dengue in India.