Researchers from Guizhou Medical University in China have made significant progress in understanding the mechanisms behind dengue fever, a viral infection transmitted by mosquitoes. Their study focused on the role of the DENV-2 non-structural protein 1 (NS1) in promoting autophagy, a cellular process activated during DENV infection.
Dengue fever has been a growing global concern, with millions of people affected each year. The lack of specific drugs for treatment and concerns about the efficacy and safety of the dengue vaccine have highlighted the need for a deeper understanding of the virus’s pathogenesis.
During DENV infection, autophagy, a cellular process that breaks down damaged or unnecessary cellular components, is activated. Previous studies have shown that DENV-2-induced autophagy promotes viral replication and energy metabolism. Understanding the role of autophagy in viral replication is crucial for developing effective therapeutic interventions.
The researchers identified NS1 as the non-structural protein involved in AMPK pathway-mediated autophagy. Through experiments, they confirmed that NS1 induces autophagy through the AMPK/ERK/mTOR signaling pathway. NS1 was found to interact with AMPK in DENV-2-infected cells, and its wing structural domain was identified as crucial for activating autophagy. NS1 was also found to bind to all three structural domains of the AMPKα subunit, indicating multiple mechanisms of NS1’s promotion of AMPK phosphorylation. LKB1, an upstream kinase responsible for AMPK activation, was also found to play a significant role in NS1-induced autophagy.
These findings provide important insights into the role of NS1 in DENV-induced autophagy and have implications for the development of therapeutic strategies targeting NS1. As NS1 is involved in various aspects of DENV pathogenesis, further research on its interactions and functions is crucial for combating dengue fever.
This study brings us one step closer to developing effective drugs for this global health threat. The research findings have been published in the Virology Journal, contributing to our understanding of the mechanisms behind DENV-induced autophagy and offering valuable insights for the development of potential therapeutic interventions.