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Updated: Dec 31, 2025

MicroRNA-based Regulation of Picornavirus Tropism
Published on: February 6, 2017
MicroRNA-221 inhibits human papillomavirus 16 E1-E2 mediated DNA replication through activating SOCS1/Type I IFN
Haikong Lu1, Xin Gu1
1Department of Sexually Transmitted Disease Institute, Shanghai Skin Disease Hospital Shanghai 200050, China.
Abstract:
Human Papillomavirus (HPV) 16 infection has led to clinical disorders and is considered one of the important causes of human cervical cancer. Recently, microRNAs (miRNAs) have been proven to play an important role in many viral infections through regulating the Type I IFN immune response. However, reports concerning the role of miRNAs in HPV 16 infection are unclear. The aim of this study was to identify and evaluate the potential functions of miRNAs in HPV 16 replication and reveal the detailed mechanism for regulating IFN immune response. Using microarray and qRT-PCR assays, microRNA-221 (miR-221) was found to be significantly up-regulated in the serum samples from patients with HPV 16 infection, as well as in HPV 16-positive cervical cancer cells. miR-221 overexpression inhibited, while miR-221 knockdown facilitated HPV 16 E1-E2 mediated DNA replication in vitro. Moreover, overexpression of miR-221 was associated with upregulation of IFN-α and IFN-β at mRNA and protein levels in infected cells. Conversely, IFN-α and IFN-β mRNA or protein expression was significantly downregulated during inhibition of miR-221. Subsequently, we demonstrated that upregulation of miR-221 promoted the expression of representative interferon stimulated genes (ISGs) such as myxovirus protein A (MxA), 2',5'-oligoadenylate synthetases (OAS) and murine IFN-stimulated gene 15 (ISG15). In contrast, miR-221 inhibition significantly decreased ISGs expression. Furthermore, we found that suppressor of cytokine signaling 1 (SOCS1), a suppressor of interferon signaling pathway, was a direct target of miR-221 and overexpression of SOCS1 reversed the effects of miR-221 on the IFN-I response and HPV 16 E1-E2 mediated DNA replication. Collectively, the findings provide new evidence that miR-221 could inhibit HPV 16 E1-E2 mediated DNA replication through the SOCS1/Type I IFN signaling pathway suggesting it may be a novel anti-HPV therapeutic target.
Insights
MicroRNA-221 (miR-221) inhibits Human Papillomavirus (HPV) 16 replication by targeting SOCS1 and modulating the Type I Interferon (IFN) immune response. This discovery suggests miR-221 as a potential therapeutic target for HPV infections.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Human Papillomavirus (HPV) 16 is a major cause of cervical cancer.
- MicroRNAs (miRNAs) are implicated in viral infections and immune responses.
- The role of miRNAs in HPV 16 infection requires further elucidation.
Purpose of the Study:
- To identify and evaluate miRNAs involved in HPV 16 replication.
- To understand the mechanism of miRNA regulation of the Type I Interferon (IFN) immune response in HPV 16 infection.
Main Methods:
- Microarray and quantitative real-time PCR (qRT-PCR) assays were used.
- In vitro experiments assessed HPV 16 DNA replication upon miR-221 manipulation.
- Western blotting and qRT-PCR analyzed protein and mRNA expression of IFN-α, IFN-β, and Interferon Stimulated Genes (ISGs).
- Luciferase reporter assays identified direct targets of miR-221.
Main Results:
- MicroRNA-221 (miR-221) was significantly upregulated in HPV 16-infected patients and cells.
- miR-221 overexpression inhibited HPV 16 replication, while knockdown facilitated it.
- miR-221 upregulated IFN-α, IFN-β, and ISG expression, including MxA, OAS, and ISG15.
- Suppressor of Cytokine Signaling 1 (SOCS1) was identified as a direct target of miR-221.
Conclusions:
- miR-221 inhibits HPV 16 replication by targeting SOCS1, thereby modulating the Type I IFN signaling pathway.
- miR-221 plays a crucial role in the host's immune response to HPV 16 infection.
- miR-221 represents a potential novel therapeutic target for HPV infections.
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