NRZ complex facilitates virus infection via enhancing ER-LD contacts

Area of Science:

• Cell Biology
• Virology
• Molecular Biology

Background:

• Lipid droplets (LDs) and endoplasmic reticulum (ER) interactions are vital for cellular lipid metabolism.
• The role of ER-LD contacts in viral pathogenesis is largely unknown.
• Hepatitis C virus (HCV) infection impacts cellular lipid metabolism.

Purpose of the Study:

• To investigate how viruses, specifically HCV, exploit ER-LD contacts.
• To identify host factors mediating ER-LD association during viral infection.
• To explore the conserved function of identified factors in other viral infections.

Main Methods:

• Utilized targeted screening of ER-LD tethering proteins.
• Performed co-immunoprecipitation assays to study protein interactions.
• Assessed viral infection levels upon depletion or expression of specific host factors.
• Investigated the impact of NRZ complex on ER-LD contacts.

Main Results:

• HCV infection significantly increases LDs abundance and enhances ER-LD contacts.
• The NRZ complex (NAG, RINT1, ZW10) is essential for HCV-induced ER-LD association and viral replication.
• RINT1 and ZW10 directly interact with the HCV E1 envelope protein.
• NRZ complex depletion impairs Dengue virus (DENV) and Zika virus (ZIKV) infections, indicating a conserved role.

Conclusions:

• The NRZ complex acts as a critical host factor mediating ER-LD contacts for viral propagation.
• HCV utilizes the NRZ complex to enhance ER-LD association, promoting infection.
• This study reveals a conserved mechanism of virus-host interaction involving inter-organelle tethering complexes, highlighting potential antiviral targets.