STUDIES ON THE ROLE OF TRIM69 IN DENV NS3 PROTEASE UBIQUITINATION AND THE INHIBITION MECHANISM OF HUMAN NEUTROPHIL ELASTASE

Abstract

Bacterial and viral diseases have plagued the world for centuries. During the infection process, the host elicits different defense mechanisms in response to the invading pathogens. The immune system effector molecules including immune cells and interferon stimulated genes function to clear the pathogen. However, imbalances in the production of effector molecules such as human neutrophil elastase/hNE have been associated with chronic inflammatory lung conditions. As such Ecotin, a bacterium produced hNE inhibitor was exploited as scaffold as for design of potent hNE inhibitor. On the other hand, following Dengue infection, the host overexpress the E3 ligase TRIM69 as an antiviral restriction factor to curb the viral replication and spread. In efforts to understand the molecular basis of TRIM69 antiviral activity against DENV protease NS2B-NS3, the interaction interface between the two was mapped using HDXMS. This revealed a conserved mode of action by which the host exploits TRIM69 as a pan-antiviral factor.