title: Zika Virus-Induced Microcephaly and Its Possible Molecular Mechanism.
abstract: Zika virus is an arthropod-borne re-emerging pathogen associated with the global pandemic of 2015-2016. The devastating effect of Zika viral infection is reflected by its neurological manifestations such as microcephaly in newborns. This scenario evoked our interest to uncover the neurotropic localization, multiplication of the virus, and the mechanism of microcephaly. The present report provides an overview of a possible molecular mechanism of Zika virus-induced microcephaly based on recent publications. Transplacental transmission of Zika viral infection from mother to foetus during the first trimester of pregnancy results in propagation of the virus in human neural progenitor cells (hNPCs), where entry is facilitated by the receptor (AXL protein) leading to the alteration of signalling and immune pathways in host cells. Further modification of the viral-induced TLR3-mediated immune network in the infected hNPCs affects viral replication. Downregulation of neurogenesis and upregulation of apoptosis in hNPCs leads to cell cycle arrest and death of the developing neurons. In addition, it is likely that the environmental, physiological, immunological, and genetic factors that determine in utero transmission of Zika virus are also involved in neurotropism. Despite the global concern regarding the Zika-mediated epidemic, the precise molecular mechanism of neuropathogenesis remains elusive.
authors.affiliation: Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India.
authors.forename: Md Imam
authors.initials: MI
authors.lastname: Faizan
authors.forename: Mohd
authors.initials: M
authors.lastname: Abdullah
authors.forename: Sher
authors.initials: S
authors.lastname: Ali
authors.forename: Irshad H
authors.initials: IH
authors.lastname: Naqvi
authors.forename: Anwar
authors.initials: A
authors.lastname: Ahmed
authors.forename: Shama
authors.initials: S
authors.lastname: Parveen
mesh_terms: D017209:Apoptosis; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008831:Microcephaly / Q000209:etiology* / Q000503:physiopathology / Q000821:virology; D058953:Neural Stem Cells / Q000502:physiology / Q000821:virology*; D055495:Neurogenesis; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000821:virology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology; D014779:Virus Replication; D000071244:Zika Virus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D000071243:Zika Virus Infection / Q000150:complications* / Q000503:physiopathology / Q000635:transmission / Q000821:virology; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D011518:Proto-Oncogene Proteins; D011991:Receptors, Virus; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase