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 journalArticlepeer-review

22 Citations (Scopus)


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
Issue number11
Early online date17 May 2018
Publication statusPublished - 1 Nov 2018
Externally publishedYes


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