The clinical spectrum and immunopathological mechanisms underlying ZIKV-induced neurological manifestations

Abstract

Since the 2015 to 2016 outbreak in America, Zika virus (ZIKV) infected almost 900,000 patients. This international public health emergency was mainly associated with a significant increase in the number of newborns with congenital microcephaly and abnormal neurologic development, known as congenital Zika syndrome (CZS). Furthermore, Guillain–Barré syndrome (GBS), a neuroimmune disorder of adults, has also been associated with ZIKV infection. Currently, the number of ZIKV-infected patients has decreased, and most of the cases recently reported present as a mild and self-limiting febrile illness. However, based on its natural history of a typical example of reemerging pathogen and the lack of specific therapeutic options against ZIKV infection, new outbreaks can occur worldwide, demanding the attention of researchers and government authorities. Here, we discuss the clinical spectrum and immunopathological mechanisms underlying ZIKV-induced neurological manifestations. Several studies have confirmed the tropism of ZIKV for neural progenitor stem cells by demonstrating the presence of ZIKV in the central nervous system (CNS) during fetal development, eliciting a deleterious inflammatory response that compromises neurogenesis and brain formation. Of note, while the neuropathology of CZS can be due to a direct viral neuropathic effect, adults may develop neuroimmune manifestations such as GBS due to poorly understood mechanisms. Antiganglioside autoantibodies have been detected in multiple patients with ZIKV infection–associated GBS, suggesting a molecular mimicry. However, further additional immunopathological mechanisms remain to be uncovered, paving the way for new therapeutic strategies.

Zika virus induced microcephaly and aberrant hematopoietic cell differentiation modeled in novel neonatal humanized mice

“…Clinically, CZS has been shown to encompass microcephaly with neural pathologies and ocular anomalies ( 57 ). Brain structure disruptions have been observed, particularly abnormal gyral patterns, thin cerebral cortices, larger amount of fluid spaces (porencephaly), calcification of subcortical regions, corpus collosum abnormalities, asymmetric and increased ventricles (ventriculomegaly and hydrocephalus), lesser amounts of white matter, and cerebellar hypoplasia ( 57 – 60 ). To determine if our model recapitulates brain anomalies similar to those seen clinically with CZS, we next characterized the neuropathology of the brain in these ZIKV-infected hu-mice.…”

Peripheral nervous system is injured by neutrophil extracellular traps (NETs) elicited by nonstructural (NS) protein‐1 from Zika virus

“…ZIKV has been recognized as a cause of GBS and microcephaly 44 . Although several studies have addressed the role of ZIKV in microcephaly, the pathogenesis of ZIKV‐associated GBS remains unclear.…”

Immunopathogenesis of viral infections in neurological autoimmune disease

“…Zika virus is one of the members of the Flaviviridae family, with a single-stranded positive-sense RNA genome, which can participate in the development of some central and peripheral nervous system disorders such as Guillain-Barré syndrome (GBS), transverse myelitis (TM), and meningoencephalitis [ 23 , 24 ]. Although it was shown that Zika virus infection can be presented wide range of neurological manifestations [ 25 ], few studies reported detection of Zika virus in patients with MS [ 26 ]. It is suggested that zika virus can induce autoimmune reaction against neural cells that can mimic the presentation of MS [ 27 ].…”