Cracking the Zika Virus Code: from Pathogenesis to Global Health Challenges

Introduction: The Zika virus (ZIKV), a mosquito-borne flavivirus, has emerged as a global health concern due to its rapid spread and association with severe congenital and neurological complications. In addition to Aedes mosquito transmission, alternative routes include sexual contact, maternal-fetal transfer, blood transfusion, and organ transplantation. This review provides an updated synthesis of ZIKV pathogenesis, clinical manifestations, diagnostics, and preventive strategies. Methods: A comprehensive literature review was conducted using PubMed, Scopus, Web of Science, and Google Scholar, covering publications from 2007 to 2024. Studies focusing on ZIKV transmission, molecular mechanisms, immune evasion, neurological and reproductive complications, diagnostic innovations, and vaccine development were critically evaluated and summarized. Results: ZIKV infects host cells via receptors such as AXL, DC-SIGN, and TIM-1, enabling immune evasion, neurotropism, and persistence in reproductive tissues. The infection is linked to Guillain–Barré syndrome in adults and microcephaly in newborns. Viral persistence in semen and female reproductive organs raises concerns about prolonged transmission. Diagnostic advances, particularly RT-PCR and emerging point-of-care technologies, have improved early detection. Vaccine candidates, antiviral agents, and vector-control approaches are under active investigation. Discussion: ZIKV’s diverse transmission routes and ability to target neural and reproductive tissues highlight its complexity and significance. Despite reduced global incidence, sporadic outbreaks and continued endemic transmission underscore the risk of resurgence. Current diagnostic and preventive measures remain limited by cross-reactivity, accessibility, and incomplete validation. Conclusion: ZIKV remains a pressing health threat. Strengthened surveillance, accelerated vaccine development, and integration of innovative diagnostics with vector-control strategies are essential to mitigate future outbreaks.