Poly(dA:dT) Suppresses HSV-2 Infection of Human Cervical Epithelial Cells Through RIG-I Activation.

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• Epithelial cells in the female reproductive tract (FRT) are crucial for initial antiviral defense.
• Interferon (IFN) signaling pathways, activated by double-stranded (ds) DNA analogs like Poly(dA:dT), mediate antiviral immunity.

Purpose of the Study:

• To investigate the inhibitory effect of Poly(dA:dT) on herpes simplex virus type 2 (HSV-2) infection in human cervical epithelial cells.
• To elucidate the underlying molecular mechanisms of Poly(dA:dT)-mediated antiviral activity.

Main Methods:

• Treatment of human cervical epithelial cells (End1/E6E7) with Poly(dA:dT).
• Infection of treated cells with HSV-2.
• Measurement of intracellular IFN and IFN-stimulated genes (ISGs) expression.
• Assessment of the role of RIG-I using RIG-I knockout cells.

Main Results:

• Poly(dA:dT) significantly inhibited HSV-2 infection in End1/E6E7 cells.
• Poly(dA:dT) treatment upregulated the expression of various intracellular IFNs and ISGs (ISG15, ISG56, OAS1, OAS2, MxA, MxB, Viperin, GBP5).
• RIG-I activation was identified as the primary mediator of Poly(dA:dT)'s antiviral effects, as RIG-I knockout cells showed abolished inhibition and induction.

Conclusions:

• Poly(dA:dT) demonstrates potent antiviral activity against HSV-2 in cervical epithelial cells.
• The mechanism involves RIG-I-dependent induction of IFNs and ISGs.
• AT-rich dsDNA-based strategies hold promise for controlling HSV-2 mucosal transmission.