Lnc-DARVR/miR-365-1-5p/LAMB1 axis regulates rotavirus replication via the complement C3 pathway

Area of Science:

• Immunology
• Molecular Biology
• Virology

Background:

• Long non-coding RNAs (lncRNAs) are crucial in host-virus interactions, but their role in the complement system's antiviral defense against rotavirus is unclear.
• Understanding lncRNA regulation of antiviral immunity is vital for developing new therapies against viral infections.

Purpose of the Study:

• To identify and characterize a novel lncRNA involved in rotavirus (RV) infection.
• To elucidate the molecular mechanism by which this lncRNA regulates host antiviral responses.
• To explore the potential of lncRNAs and complement factors as therapeutic targets for rotavirus.

Main Methods:

• Identification of a novel intergenic lncRNA, DARVR, in MA104 cells infected with rotavirus.
• Investigation of the regulatory pathway involving DARVR, miR-365-1-5p, LAMB1, and complement factor C3.
• Assessment of DARVR's effect on rotavirus replication and complement C3 activity.

Main Results:

• DARVR was identified as a novel lncRNA that inhibits rotavirus replication.
• DARVR acts as a competing endogenous RNA (ceRNA) for miR-365-1-5p, thereby upregulating LAMB1 expression.
• Upregulation of LAMB1 enhances complement C3 activity, leading to inhibition of rotavirus replication.

Conclusions:

• This study reveals a novel lncRNA, DARVR, that plays a significant role in the innate immune response to rotavirus infection.
• DARVR enhances complement C3-mediated antiviral activity through a ceRNA mechanism involving miR-365-1-5p and LAMB1.
• These findings highlight the potential of targeting lncRNAs and complement factors for therapeutic strategies against rotavirus and other viral infections.