Microscopy analysis of Zika virus morphogenesis in mammalian cells

Lucio Ayres Caldas,Wanderley De Souza,Renata Campos Azevedo,Jerson Lima Da Silva

doi:10.1038/s41598-020-65409-y

Abstract

Zika virus (ZIKV) is an arbovirus that recently emerged in the Americas as an important pathogen mainly because of its expanded pathogenesis, and elevated tropism for neuronal cells, transposition across the placental barrier, and replication in reproductive tract cells. Thus, transmission modes are eventually independent of an invertebrate vector, which is an atypical behavior for the flavivirus genus and indicates the need to study the replication of this virus in different cell types. Although ZIKV became a target for public health programs, the interaction of this flavivirus with the infected cell is still poorly understood. Herein, we analyzed the main stages of virus morphogenesis in mammalian cells, from establishment of the viroplasm-like zone to viral release from infected cells, using super-resolution fluorescence microscopy and electron microscopy. In addition, we compared this with other host cell types and other members of the Flaviviridae family that present a similar dynamic.

Highlights

Zika virus (ZIKV) is an arbovirus that recently emerged in the Americas as an important pathogen mainly because of its expanded pathogenesis, and elevated tropism for neuronal cells, transposition across the placental barrier, and replication in reproductive tract cells
Modification of the eukaryotic endomembrane system caused by some flavivirus infections results in viral replication that is confined to a locus, which concentrates cellular and viral factors that are crucial for virus replication
The close association of ZIKV morphogenesis with these endoplasmic reticulum-derived membranes suggests that transport of the nascent virions occurs through the secretory pathway towards the host cell plasma membrane, from which they acquire their cell-derived lipid bilayer that encapsulates the C-protein[32]

Summary

Introduction

Zika virus (ZIKV) is an arbovirus that recently emerged in the Americas as an important pathogen mainly because of its expanded pathogenesis, and elevated tropism for neuronal cells, transposition across the placental barrier, and replication in reproductive tract cells. Discovered in a sentinel Rhesus monkey of the Zika forest in Uganda in 1947, Zika virus (ZIKV) was isolated for the first time from mosquitoes 1 year later[1]. This previously underestimated arbovirus recently reached the front pages of the main newspapers throughout the world as an international public health emergency. Flaviviridae members’ replication is cytosolic and it typically causes a rearrangement in the ER in the host, allowing the formation of a viroplasm-like structure, or the viral replication organelle (VRO)[13]. Viral non-structural proteins are involved in ER membrane invaginations, www.nature.com/scientificreports where the viral (−)RNA intermediate synthesis is supposed to occur. Cisternae containing viral particles are transported towards the plasma membrane limits, while furin enzymes cleave the M glycoprotein, complementing the virion’s maturation[17] before egress

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