The Evolution of Dengue Virus in India

The evolution of dengue virus (DENV) is highly modulated by pathogen transmission bottlenecks and immunological pressures. These evolutionary events lead to mutations that cause antigenic changes and the replacement of DENV genotypes, which are directly correlated with epidemic magnitude and severe disease. India bears a disproportionately high dengue burden, accounting for nearly one-third of global cases, making it a persistent public health challenge. The periodic recurrence of outbreaks and cocirculation of all four serotypes pose challenges in disease control efforts. Nearly half of the country's population is seropositive for dengue, with varying seropositivity by age and geographical location. The spatiotemporal dynamics of prevalent serotypes in India are often associated with changes in transmission patterns, leading to cyclic outbreaks approximately every 2-3 years. Although multiple genotypes of serotypes have been recorded worldwide, Indian genotypes are highly diverged, with strong intermixing with neighboring countries. This review explores the mechanisms that drive DENV evolution underlying viral transmission bottlenecks, intrahost genetic diversity, and host immune responses. I also highlight the role of preexisting cross-reactive immunity and concurrent coinfections involving more than one serotype or other genetically similar arboviruses in the evolution of DENV. Finally, I outline the impact of DENV evolution on vaccine development and deployment in India.