Dengue and Zika: Mosquito-borne viral infections

The four dengue virus serotypes and Zika are closely related RNA viruses that share the same mosquito vector and circulate in overlapping geographic ranges. Due to urbanization and climate change, dengue- and Zika-transmitting mosquitos are expanding their habitat, and these viruses now pose significant threats to global health, affecting over half the world’s population. Due to their phylogenetic and antigenic relatedness, the immune response to dengue and Zika viruses are highly cross-reactive. These cross-reactive immune responses may play a protective or pathogenic role depending on the context, such as the sequence of viral infections or interval between viral infections. Thus, the dengue/Zika field has been focused on addressing the following questions related to the immunological cross-reactivity between the dengue serotypes and Zika:

1. why has it been challenging to develop a dengue vaccine despite 70 years of effort?
2. how does a previous exposure to dengue virus influence subsequent infection with Zika virus?
3. how does a prior exposure to dengue virus impact Zika viral evolution?

Our studies using dengue mouse models have demonstrated that antibodies can increase dengue infection and convert a mild illness into a lethal disease, a process termed antibody-dependent enhancement (ADE). ADE therefore represents the key challenge for developing a safe and effective dengue vaccine. Our studies using mouse models of sequential dengue-Zika virus infections have shown that prior dengue immunity confers cross-protection against subsequent infection with Zika virus, suggesting that a universal dengue-Zika vaccine may be effective against all five viruses (i.e., the four dengue serotypes and Zika). Finally, our ongoing studies have revealed that prior dengue immunity also influences the evolution of Zika virus. This finding highlights the capacity of RNA viruses to evade the host immune response and cause emerging and re-emerging infectious diseases of global significance.