MCV-miR-M1 Targets the Host-Cell Immune Response Resulting in the Attenuation of Neutrophil Chemotaxis

The Journal of Investigative Dermatology
Pouria AkhbariJames R Boyne

Abstract

Virus-encoded microRNAs are emerging as key regulators of persistent infection and host-cell immune evasion. Merkel cell polyomavirus, the predominant etiological agent of Merkel cell carcinoma, encodes a single microRNA, MCV-miR-M1, which targets the oncogenic Merkel cell polyomavirus large T antigen. MCV-miR-M1 has previously been shown to play an important role in the establishment of long-term infection, however, the underlying mechanism is not fully understood. A key unanswered question is whether, in addition to autoregulating large T antigen, MCV-miR-M1 also targets cellular transcripts to orchestrate an environment conducive to persistent infection. To address this, we adopted an RNA sequencing-based approach to identify cellular targets of MCV-miR-M1. Intriguingly, bioinformatics analysis of transcripts that are differentially expressed in cells expressing MCV-miR-M1 revealed several genes implicated in immune evasion. Subsequent target validation led to the identification of the innate immunity protein, SP100, as a direct target of MCV-miR-M1. Moreover, MCV-miR-M1-mediated modulation of SP100 was associated with a significant decrease in CXCL8 secretion, resulting in the attenuation of neutrophil chemotaxis toward Mer...Continue Reading

Citations

Feb 9, 2020·Cancers·Alessia GalloPier Giulio Conaldi
Sep 16, 2020·Non-coding RNA·Alessia GalloPier Giulio Conaldi
Jun 29, 2018·International Journal of Molecular Sciences·Aelita KonstatinellUgo Moens
Oct 3, 2018·Current Opinion in Virology·Nathan A KrumpJianxin You
Apr 18, 2021·The Journal of Investigative Dermatology·Miranda C LahmanAude G Chapuis
Jul 3, 2021·International Journal of Molecular Sciences·Karolina StachyraAnna M Czarnecka
Aug 8, 2021·International Journal of Molecular Sciences·Valeria PietropaoloUgo Moens

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