Zika virus Pathogenesis and Targeted Intervention Strategies

Zika virus (ZIKV), a mosquito-borne member of the Flaviviridae family, is primarily transmitted via the bite of Aedes aegypti mosquitoes but can also be spread through sexual contact and vertical transmission. Infection with ZIKV causes Zika fever and Guillain-Barré syndrome (GBS); more importantly, maternal infection during pregnancy can result in severe neurodevelopmental disorders, such as fetal microcephaly. Although the World Health Organization declared the Zika outbreak a Public Health Emergency of International Concern (PHEIC) in 2016, and extensive research has since been conducted, no approved vaccines or therapeutic drugs are currently available. Recent studies have shown that various ZIKV-encoded proteins participate in host-barrier breaching, regulation of tissue tropism, interference with neurodevelopment, mediation of neurotoxicity, and evasion of type I interferon (IFN-I) immune responses, thereby advancing the development of vaccines and antiviral drugs targeting viral proteins. However, the complete mechanisms by which viral proteins synergistically mediate pathogenesis, the clinical significance of antibody-dependent enhancement (ADE) and its prevention and control strategies, and the practical barriers to clinical translation of protein-targeted interventions have not been systematically elucidated. This review is structured around viral proteins as a central framework: it summarizes the molecular mechanisms by which multiple ZIKV proteins synergistically regulate pathogenic processes; reviews the current research basis and response strategies for flavivirus ADE, and outlines unresolved scientific questions; and discusses progress in vaccines and antiviral drugs targeting viral proteins, with emphasis on evidence gaps and clinical translation barriers. By integrating existing findings and unresolved scientific questions, this review provides a research-gap-oriented theoretical reference for basic ZIKV research and clinical translation of prevention and control strategies.