A Novel Mycovirus Evokes Transcriptional Rewiring in the Fungus Malassezia and Stimulates Beta Interferon Production in Macrophages

Author:

Applen Clancey Shelly1,Ruchti Fiorella23,LeibundGut-Landmann Salomé23ORCID,Heitman Joseph1,Ianiri Giuseppe1ORCID

Affiliation:

1. Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA

2. Section of Immunology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland

3. Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland

Abstract

Malassezia species represent the most common fungal inhabitant of the mammalian skin microbiome and are natural skin commensal flora. However, these fungi are also associated with a variety of clinical skin disorders. Recent studies have reported associations of Malassezia with Crohn’s disease and pancreatic cancer, further implicating this fungal genus in inflammatory and neoplastic disease states. Because M. sympodialis has lost genes involved in RNA interference (RNAi), we hypothesized Malassezia could harbor dsRNA mycoviruses. Indeed, we identified a novel mycovirus of the totivirus family in several Malassezia species and characterized the MsMV1 mycovirus of M. sympodialis . We found conditions that lead to curing of the virus and analyzed isogenic virus-infected/virus-cured strains to determine MsMV1 genetic and pathogenic impacts. MsMV1 induces a strong overexpression of transcription factors and ribosomal genes, while downregulating cellular metabolism. Moreover, MsMV1 induced a significantly higher level of beta interferon expression in cultured macrophages. This study sheds light on the mechanisms of pathogenicity of Malassezia , focusing on a previously unidentified novel mycovirus.

Funder

Swiss National Science Foundation

HHS | NIH | National Institute of Allergy and Infectious Diseases

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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