Zika Virus: A Tale of Two Lineages

Zika virus (ZIKV) was first identified in Africa in the mid-20th century and circulated for decades with limited and often unnoticed human cases. This situation changed with the emergence of the Asian lineage, responsible for large outbreaks in the Pacific and the Americas and for severe complications such as Guillain-Barré syndrome and Congenital Zika Syndrome (CZS). In contrast, the African lineage, although frequently more efficient in replication, cytopathogenicity, and mosquito transmission in experimental systems, has not been linked to comparable epidemics or congenital disease clusters. This review summarizes current knowledge on the differences between African and Asian lineages at the molecular, cellular, and epidemiological levels. It highlights how genetic variation interacts with host immunity, ecological factors, and human activity to shape epidemic potential. Understanding these interactions is essential for anticipating future outbreaks and for improving strategies to mitigate the impact of emerging arboviruses.