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

Abstract

Epithelial cells of the female reproductive tract (FRT) participate in the initial innate immunity against viral infections. Poly(dA:dT) is a synthetic analog of B form double-stranded (ds) DNA which can activate the interferon (IFN) signaling pathway-mediated antiviral immunity through DNA-dependent RNA Polymerase III. Here we investigated whether poly(dA:dT) could inhibit herpes simplex virus type 2 (HSV-2) infection of human cervical epithelial cells (End1/E6E7). We demonstrated that poly(dA:dT) treatment of End1/E6E7 cells could significantly inhibit HSV-2 infection. Mechanistically, poly(dA:dT) treatment of the cells induced the expression of the intracellular IFNs and the multiple antiviral IFN-stimulated genes (ISGs), including IFN-stimulated gene 15 (ISG15), IFN-stimulated gene 56 (ISG56), 2'-5'-oligoadenylate synthetase 1 (OAS1), 2'-5'-oligoadenylate synthetase 2 (OAS2), myxovirus resistance protein A (MxA), myxovirus resistance protein B (MxB), virus inhibitory protein, endoplasmic reticulum-associated, IFN-inducible (Viperin), and guanylate binding protein 5 (GBP5). Further investigation showed that the activation of RIG-I was largely responsible for poly(dA:dT)-mediated HSV-2 inhibition and IFN/ISGs induction in the cervical epithelial cells, as RIG-I knockout abolished the poly(dA:dT) actions. These observations demonstrate the importance for design and development of AT-rich dsDNA-based intervention strategies to control HSV-2 mucosal transmission in FRT.

• Authors: Dan-Dan Shao, Feng-Zhen Meng, Yu Liu, Xi-Qiu Xu, Xu Wang, Wen-Hui Hu, Wei Hou, Wen-Zhe Ho
• Journal: Frontiers in immunology (Front Immunol) Vol. 11 Pg. 598884 ( 2020) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 33664729 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Shao, Meng, Liu, Xu, Wang, Hu, Hou and Ho.

Chemical References

• Biomarkers
• Receptors, Immunologic
• STAT Transcription Factors
• Poly dA-dT
• Janus Kinases
• RIGI protein, human
• DEAD Box Protein 58

Topics

• Biomarkers
• Cell Line
• Cell Survival
• Cervix Uteri (metabolism, virology)
• DEAD Box Protein 58 (genetics, metabolism)
• Epithelial Cells (metabolism, virology)
• Female
• Gene Knockdown Techniques
• Herpes Genitalis (drug therapy, metabolism, virology)
• Herpesvirus 2, Human (drug effects, physiology)
• Humans
• Immunophenotyping
• Janus Kinases (metabolism)
• Mucous Membrane (metabolism, virology)
• Poly dA-dT (pharmacology)
• Receptors, Immunologic (genetics, metabolism)
• STAT Transcription Factors (metabolism)
• Signal Transduction (drug effects)
• Virus Replication (drug effects)