Understanding the Tissue Specificity of ZIKV Infection in Various Animal Models for Vaccine Development

Zika virus (ZIKV) is an arthropod-borne virus that belongs to the Flavivirus genus and is principally transmitted by Aedes aegypti mosquitoes. ZIKV infection often causes no or only mild symptoms, but it can also trigger severe consequences, including microcephaly in infants and Guillain-Barré syndrome, uveitis, and neurologic manifestations in adults. There is no ZIKV vaccine or treatment currently approved for clinical use. The primary target of ZIKV infection has been recognized as the maternal placenta, with vertical transmission to the fetal brain. However, ZIKV can also spread to multiple tissues in adults, including the sexual organs, eyes, lymph nodes, and brain. Since numerous studies have indicated that there are slightly different tissue-specific pathologies in each animal model of ZIKV, the distinct ZIKV tropism of a given animal model must be understood to enable effective vaccine development. Here, we comprehensively discussed the tissue specificity of ZIKV reported in each animal model depending on the genetic background and route of administration. This review should facilitate the selection of appropriate animal models when studying the fundamental pathogenesis of ZIKV infection, thereby supporting the design of optimal preclinical and clinical studies for the development of vaccines and therapeutics.