Cellular Organelles Reorganization During Zika Virus Infection of Human Cells

GARCÍA, CYBELE C.; VÁZQUEZ, CECILIA A.; GIOVANNONI, FEDERICO; RUSSO, CONSTANZA A.; CORDO, SANDRA M.; ALAIMO, AGUSTINA; DAMONTE, ELSA B.

Frontiers in Microbiology

Frontiers Media S.A.

Lugar: Lausanne; Año: 2020 vol. 11

Zika virus (ZIKV) is an enveloped positive stranded RNA virus belonging to the genusFlavivirus in the family Flaviviridae that emerged in recent decades causing pandemicoutbreaks of human infections occasionally associated with severe neurologicaldisorders in adults and newborns. The intracellular steps of flavivirus multiplicationare associated to cellular membranes and their bound organelles leading to anextensive host cell reorganization. Importantly, the association of organelle dysfunctionwith diseases caused by several human viruses has been widely reported in recentstudies. With the aim to increase the knowledge about the impact of ZIKV infectionon the host cell functions, the present study was focused on the evaluation of thereorganization of three cell components, promyelocytic leukemia nuclear bodies (PMLNBs), mitochondria, and lipid droplets (LDs). Relevant human cell lines including neuralprogenitor cells (NPCs), hepatic Huh-7, and retinal pigment epithelial (RPE) cells wereinfected with the Argentina INEVH116141 ZIKV strain and the organelle alterationswere studied by using fluorescent cell imaging analysis. Our results have shown thatthese three organelles are targeted and structurally modified during ZIKV infection.Considering the nuclear reorganization, the analysis by confocal microscopy of infectedcells showed a significantly reduced number of PML-NBs in comparison to uninfectedcells. Moreover, a mitochondrial morphodynamic perturbation with an increasedfragmentation and the loss of mitochondrial membrane potential was observed in ZIKVinfected RPE cells. Regarding lipid structures, a decrease in the number and volume ofLDs was observed in ZIKV infected cells. Given the involvement of these organelles inhost defense processes, the reported perturbations may be related to enhanced virusreplication through protection from innate immunity. The understanding of the cellularremodeling will enable the design of new host-targeted antiviral strategies.