Estudio del efecto de la proteína no estructural 5 del virus Zika en la producción de IFN de tipo I

Abstract

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.