Abstract
Zika virus (ZIKV) received worldwide attention over the past decade when outbreaks of the disease were found to be associated with severe neurological syndromes and congenital abnormalities. Unlike most other flaviviruses, ZIKV can spread through sexual and transplacental transmission, adding to the complexity of Zika pathogenesis and clinical outcomes. In addition, the spread of ZIKV in flavivirus-endemic regions, and the high degree of structural and sequence homology between Zika and its close cousin Dengue have raised questions on the interplay between ZIKV and the pre-existing immunity to other flaviviruses and the potential immunopathogenesis. The Zika epidemic peaked in 2016 and has affected over 80 countries worldwide. The re-emergence of large-scale outbreaks in the future is certainly a possibility. To date, there has been no approved antiviral or vaccine against the ZIKV. Therefore, continuing Zika research and developing an effective antiviral and vaccine is essential to prepare the world for a future Zika epidemic. For this purpose, an in-depth understanding of ZIKV interaction with many different pathways in the human host and how it exploits the host immune response is required. For successful infection, the virus has developed elaborate mechanisms to escape the host response, including blocking host interferon response and shutdown of certain host cell translation. This review provides a summary on the key host factors that facilitate ZIKV entry and replication and the mechanisms by which ZIKV antagonizes antiviral innate immune response and involvement of adaptive immune response leading to immunopathology. We also discuss how ZIKV modulates the host immune response during sexual transmission and pregnancy to induce infection, how the cross-reactive immunity from other flaviviruses impacts ZIKV infection, and provide an update on the current status of ZIKV vaccine development.
Highlights
Zika virus (ZIKV) is a mosquito-borne arbovirus that was brought to attention in the past decade due to its link to serious neuropathogenesis in new-borns and adults
The non-structural proteins have a variety of functions which includes evasion of host immune response, alteration of host cell signalling pathways, and replication of ZIKV RNA, all of which contributes to effective viral replication and pathogenesis [1]
This brings about the possibility of antibody-dependent enhancement, which was elicited in a few studies [67, 70], where poorly neutralizing antibodies bind to and bring viruses to infect immune cells expressing Fc receptors, increasing virion production and worsening disease outcomes
Summary
Zika virus (ZIKV) is a mosquito-borne arbovirus that was brought to attention in the past decade due to its link to serious neuropathogenesis in new-borns and adults. The non-structural proteins have a variety of functions which includes evasion of host immune response, alteration of host cell signalling pathways, and replication of ZIKV RNA, all of which contributes to effective viral replication and pathogenesis [1]. Mice treated with anti-IFNAR antibodies without T cell depletion did not suffer from disease or experience weight loss despite increased viral replication, suggesting that these T cells play an important role in the restriction of ZIKV infection only when type I IFN response is compromised [61]. Potent neutralizing ability was mostly limited to type-specific antibodies [69] This brings about the possibility of antibody-dependent enhancement, which was elicited in a few studies [67, 70], where poorly neutralizing antibodies bind to and bring viruses to infect immune cells expressing Fc receptors, increasing virion production and worsening disease outcomes.
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