Efecto de la infección del virus de Zika en la diferenciación neural de una línea celular troncal humana.

Astrocytes derived from Neural Progenitor Cells are susceptible to Zika Virus Infection

EDSON IVAN RUBIO HERNANDEZ (2023)

Zika virus (ZIKV) was first isolated in 1947. From its isolation until 2007, symptoms

of ZIKV-caused disease were limited (e.g., fever, hives, and headache); however,

during the epidemic in Brazil in 2014, ZIKV infection caused Guillain-Barré syndrome

in adults and microcephaly in fetuses and infants of women infected during

pregnancy. The neurovirulence of ZIKV has been studied using neural progenitor

cells (NPCs), brain organoids, neurons, and astrocytes. NPCs and astrocytes

appear to be the most susceptible cells of the Central Nervous System to ZIKV

infection. In this work, we aimed to develop a culture of astrocytes derived from a

human NPC cell line. We analyze how ZIKV affects human astrocytes and

demonstrate that 1) ZIKV infection reduces cell viability, increases the production of

Reactive Oxygen Species (ROS), and results in high viral titers; 2) there are changes

in the expression of genes that facilitate the entry of the virus into the cells; 3) there

are changes in the expression of genes involved in the homeostasis of the

glutamatergic system; and 4) there are ultrastructural changes in mitochondria and

lipid droplets associated with production of virions. Our findings reveal new evidence

of how ZIKV compromises astrocytic functionality, which may help understand the

pathophysiology of ZIKV-associated congenital disease.

Tesis de doctorado

MEDICINA Y CIENCIAS DE LA SALUD