DEFA1B inhibits ZIKV replication and retards cell cycle progression through interaction with ORC1

Area of Science:

• Virology
• Cell Biology
• Immunology

Background:

• Zika virus (ZIKV) poses a public health risk due to its association with microcephaly.
• Innate immune responses involve endogenous molecules and exosomes for intercellular communication.
• Exosomes can transfer viral infection-related molecules between cells.

Purpose of the Study:

• To investigate if ZIKV-induced exosomes regulate viral pathogenicity via RNA transfer.
• To identify specific molecules within ZIKV-infected exosomes.
• To understand the role of these molecules in host-pathogen interactions.

Main Methods:

• Exosomes isolated from ZIKV-infected and uninfected A549 cells.
• Human transcriptome array (HTA) for RNA profiling.
• qPCR, Western blotting, ELISA for ZIKV replication.
• CCK-8 and flow cytometry for cell proliferation and cycle analysis.
• Co-culture assays to assess exosome effects on recipient cells.

Main Results:

• Defensin alpha 1B (DEFA1B) expression significantly increased in exosomes from ZIKV-infected cells.
• Extracellular DEFA1B demonstrated anti-ZIKV activity, particularly before viral entry.
• Upregulated DEFA1B was found to retard host cell cycles.
• DEFA1B interacts with origin recognition complex 1 (ORC1), reducing its nuclear levels and retarding cell cycles in recipient cells.

Conclusions:

• DEFA1B, delivered via exosomes, exhibits anti-ZIKV activity.
• DEFA1B interacts with ORC1 to impede cell cycle progression.
• This study introduces DEFA1B as a dual-function molecule, acting as an antiviral agent and influencing cell proliferation by retarding cell cycles.