Mucolipin-2 cation channel increases trafficking efficiency of endocytosed viruses

Nicholas Rinkenberger, John W. Schoggins

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Receptor-mediated endocytosis is a cellular process commonly hijacked by viruses to enter cells. The stages of entry are well described for certain viruses, but the host factors that mediate each step are less well characterized. We previously identified endosomal cation channel mucolipin-2 (MCOLN2) as a host factor that promotes viral infection. Here, we assign a role for MCOLN2 in modulating viral entry. We show that MCOLN2 specifically promotes viral vesicular trafficking and subsequent escape from endosomal compartments. This mechanism requires channel activity, occurs independently of antiviral signaling, and broadly applies to enveloped RNA viruses that require transport to late endosomes for infection, including influenza A virus, yellow fever virus, and Zika virus. We further identify a rare allelic variant of human MCOLN2 that has a loss-of-function phenotype with respect to viral enhancement. These findings establish a mechanistic link between an endosomal cation channel and late stages of viral entry. IMPORTANCE Viruses must co-opt cellular processes to complete their life cycle. To enter cells, viruses frequently take advantage of cellular receptor-mediated endocytosis pathways. A growing number of host proteins are implicated in these viral uptake pathways. Here, we describe a new role for the gated cation channel MCOLN2 in viral entry. This endosomal protein modulates viral entry by enhancing the efficiency of viral trafficking through the endosomal system. Thus, MCOLN2-mediated enhancement of infection may represent a key vulnerability in the viral life cycle that could be targeted for therapeutic intervention.

Original languageEnglish (US)
Article numbere02314-17
JournalmBio
Volume9
Issue number1
DOIs
StatePublished - Jan 1 2018

Keywords

  • Endocytosis
  • Flavivirus
  • Influenza
  • Ion channels
  • Vesicular trafficking
  • Virus entry
  • Virus-host interactions

ASJC Scopus subject areas

  • Microbiology
  • Virology

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