Zika Virus: Immune Evasion Mechanisms, Currently Available Therapeutic Regimens, and Vaccines

Abstract

The sudden emergence of infectious pathogens such as Zika virus (ZIKV) holds global health concerns. Recent dissemination of ZIKV from Pacific to Americas with an upsurge of congenital anomalies and Guillain Barre Syndrome (GBS) in adults has created an alarming situation. High-throughput studies are in progress to understand ZIKV's mode of pathogenesis and mechanism of immune escape, yet the pathogenesis remains obscure. Mainly ZIKV's envelope (E) protein and nonstructural proteins (mainly NS1 and NS5) manipulate host cell to support viral immune escape by modulation of the interferon pathway and complement antagonism. The development of direct therapeutics for ZIKV infection is required to overcome the rapidly evolving viral threat. Currently, the existing strategies for ZIKV treatment are only supportive. Although, there is no prophylactic or therapeutic vaccine presently available, however, recent efforts have brought up ZIKV vaccines into clinical trial phase 1. This review presents the highlights of recent advances in understanding immune evasion strategies adapted by ZIKV and existing therapies against the virus.

Zika Virus Non-structural Protein 4A Blocks the RLR-MAVS Signaling

“…It has been established that flaviviruses have evolved complex mechanisms to avoid the host immune responses including the RLR signaling [reviewed by Asif et al (2017) and Chen et al (2017) ]. As a new re-emerging flavivirus, ZIKV has recently attracted much public attention for its potential association with neonatal microcephaly and adult Guillain-Barre Syndrome ( Asif et al, 2017 ). Its pathogenesis, however, remains largely obscure.…”

Insights from the sequence similarity of Zika virus proteins with the Human nerve proteins

“…During viral entry into the cell, the polyprotein induces genome penetration in host cytoplasm and migration into host cell nucleus where it modulates host functions [ 37 ]. The similarities identified in Nestin, Bombesin, Galanin, Calcium Binding Protein and Neuromodulin to their counterpart polyprotein C in ZIKV could help us identify peptide sequences which can regulate host cell [ 38 ].…”

The journey of Zika to the developing brain

“…A study by Liang et al [133] suggested that the NS4A and NS4B proteins encoded in the ZIKV genome cooperate in order to inhibit the activation of Akt, thus inhibiting downstream signalling via this pathway in NPCs. Preliminary studies have indicated that the NS4A and NS4B protein complex is able to inhibit PI3K (phosphatidylinositide 3 kinase), the upstream activator of Akt, thereby terminating the Akt-mTOR signalling cascade [134]; however, this phenomenon is not well understood and requires further investigation. Likewise, a correlation between Dengue virus (DENV) infection and decreased activity of mTORC1 has been found [135].…”