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

Pouria Akhbari, Desmond Tobin, Krzysztof Poterlowicz, Wayne Roberts, James R. Boyne

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 Merkel cells harboring synthetic Merkel cell polyomavirus. Based on these observations, we propose that MCV-miR-M1 targets key immune response regulators to help facilitate persistent infection, which is a prerequisite for cellular transformation in Merkel cell carcinoma.

Original languageEnglish
Pages (from-to)2343-2354
Number of pages12
JournalJournal of Investigative Dermatology
Volume138
Issue number11
Early online date17 May 2018
DOIs
Publication statusPublished - 1 Nov 2018
Externally publishedYes

Fingerprint

Merkel cell polyomavirus
Chemotaxis
Neutrophils
Cells
Merkel Cell Carcinoma
MicroRNAs
Immune Evasion
Infection
Polyomavirus Transforming Antigens
Merkel Cells
Viral Tumor Antigens
Bioinformatics
Artificial Cells
Viruses
Genes
Computational Biology
Innate Immunity
Modulation
RNA
Proteins

Cite this

Akhbari, Pouria ; Tobin, Desmond ; Poterlowicz, Krzysztof ; Roberts, Wayne ; Boyne, James R. / MCV-miR-M1 Targets the Host-Cell Immune Response Resulting in the Attenuation of Neutrophil Chemotaxis. In: Journal of Investigative Dermatology. 2018 ; Vol. 138, No. 11. pp. 2343-2354.
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MCV-miR-M1 Targets the Host-Cell Immune Response Resulting in the Attenuation of Neutrophil Chemotaxis. / Akhbari, Pouria; Tobin, Desmond; Poterlowicz, Krzysztof; Roberts, Wayne; Boyne, James R.

In: Journal of Investigative Dermatology, Vol. 138, No. 11, 01.11.2018, p. 2343-2354.

Research output: Contribution to journalArticle

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