Zika virus induced cellular remodelling

Abstract

Summary Zika virus (ZIKV) has been associated with morbidities such as Guillain-Barré, infant microcephaly, and ocular disease. The spread of this positive-sense, single-stranded RNA virus and its growing public health threat underscore gaps in our understanding of basic ZIKV virology. To advance knowledge of the virus replication cycle within mammalian cells, we use serial section three-dimensional electron tomography to demonstrate the widespread remodeling of intracellular membranes upon infection with ZIKV. We report extensive structural rearrangements of the endoplasmic reticulum and reveal stages of the ZIKV viral replication cycle. Structures associated with RNA genome replication and virus assembly are observed integrated within the endoplasmic reticulum, and we show viruses in transit through the Golgi apparatus for viral maturation, and subsequent cellular egress. This study characterizes in detail the three-dimensional ultrastructural organization of the ZIKV replication cycle stages. Our results show close adherence of the ZIKV replication cycle to the existing flavivirus replication paradigm.

Endoplasmic reticulum: a focal point of Zika virus infection

“…Interestingly, CM aggregates are not observed in ZIKV-infected neural progenitor cells, suggesting cell-type-specific factors are required to develop the CM [32]. No discernible difference in the CM structure is observed between the African and Asian ZIKV strains [36,37].…”

“…Recent transmission electron microscopy analyses on ZIKV-infected cells frequently observed significant expansion of the ER [32,35,36]. This structural modification typically consisted of proliferating ER lamellae and dilated ER lumen, which cumulatively increases the overall ER size and volume.…”

“…ZIKV infection also forms distinct aggregates of intricate ER tubular network that resembles sponge-like matrix called the convoluted membranes (CM) ( Fig. 1) [32,[35][36][37]. CM aggregates are frequently seen bordering ZIKV virions and other ZIKV-induced structures, with occasional virions also found within the CM itself [32,36].…”

“…1) [32,[35][36][37]. CM aggregates are frequently seen bordering ZIKV virions and other ZIKV-induced structures, with occasional virions also found within the CM itself [32,36]. The function of the CM in ZIKV infection is unclear; nevertheless, evidence from other flaviviruses studies suggest that the CM possesses roles closely associated to protein synthesis and processing [18].…”

“…Next, vesicle packets (VPs) are also commonly observed in ZIKV-infected cells ( Fig. 1) [32,[35][36][37]. VPs refers to an aggregate of closely packed single-membrane vesicles that are encapsulated within an ER cisterna.…”