Evaluating the pandemic potential of Zika virus in a changing global landscape

As of 2024, the World Health Organization declared the Zika virus (ZIKV), an emerging flavivirus, as a high-priority pathogen with the potential to cause future Public Health Emergencies of International Concern. Although the last major outbreak of ZIKV occurred in 2015-2016, ongoing 'silent' transmission in the Americas, Asia, and Africa indicates that ZIKV remains a global threat. Recent research highlights possible reintroduction of ZIKV into sylvatic reservoirs, identifies mosquito immune cells essential for viral dissemination, uncovers viral protein mutations that affect neurovirulence, and examines how cross-reactive flavivirus immunity shapes disease outcomes. Despite these advances, major challenges persist in surveillance, diagnosis, and the development of effective vaccines or therapeutics. This review synthesizes current knowledge on the global burden of ZIKV, transmission dynamics, and adaptive evolution, emphasizing factors that drive its epidemic potential. Continued research and a One Health approach are crucial to improve understanding of ZIKV biology and strengthen preparedness for future outbreaks.