Estudio del efecto de la proteína no estructural 5 del virus Zika en la producción de IFN de tipo I
Author
Hernández Cabrera, RaúlDate
2024Abstract
The Zika virus (ZIKV) differs from other flaviviruses due to its neurotropism and neurotoxicity,
which are associated with the most deleterious effects of the infection, such as Congenital
Zika Syndrome (CZS) and Guillain-Barré Syndrome. Both the blood-brain barrier and the
placental barrier seem to be disrupted, and the ability of the nonstructural protein 5 (NS5) to
interfere with the innate immune response, especially in the production of type I interferon
(IFN-I), is crucial in this process. Here, we demonstrate the impact of the ZIKV NS5 viral
protein on the innate immune response in HEK-Lucia cells, a reporter cellular model for IFN-I
expression. We discovered that promoting post-translational modifications (PTMs) such as
ubiquitination, SUMOylation, or blocking autophagy abolishes NS5 ability to inhibit IFN-I. We
revealed that Lysine 330 of NS5 directs its capacity to subvert IFN-I expression in response
to infection. Our findings demonstrate that PTMs are critical in NS5 suppression of IFN-I. ZIKV
utilizes the cellular ubiquitination machinery to facilitate evasion of the immune response.
Given the global impact of ZIKV and its potential for a pandemic, understanding this virus
better is crucial for developing prevention, control, and potential treatment strategies.