Zika virus and microcephaly: A review of the molecular interactions

The Zika virus (ZIKV) is a tropical and subtropical emergent pathogen, with main clinical manifestations of low fever, headache, myalgia, arthralgia in the small joints of the hands and feet, non-purulent conjunctivitis, ocular pain, prostration, and pruritic maculopapular rash. Furthermore, the most feared complication of this viral infection is microcephaly, caused by the interaction between ZIKV and cells from the fetal central nervous system (CNS). Identifying the mechanism and factors linked to the entry of ZIKV into human cells, particularly in the fetus during the first developmental months, is currently the greatest challenge in understanding the tropism and pathogenesis of ZIKV. Thus, this review aims to assess the ZIKV–human molecular interaction, the main cellular receptors involved in the virus and host, the viral infection process, and microcephaly neuropathogenesis. During ZIKV–human host interaction, the virus binds to host cell membrane receptors, followed by internalization (through endocytic vesicles) and inhibition of the innate immune response, similar to the normal process of receptor signaling activation. Infection of human fetuses by ZIKV leads to cell cycle deregulation, activating cell death by apoptosis, and microcephaly. Blocking the interaction between the virus and specific membrane receptors may be a good strategy to prevent ZIKV infection, particularly in pregnant women during the first months of fetal development. Thus, knowledge of the whole ZIKV–host interaction process may help in designing novel therapies or targets for drugs to prevent the death of fetal CNS cells and microcephaly.