The interplay between viperin antiviral activity, lipid droplets and Junín mammarenavirus multiplication

Virology. 2018 Jan 15;514:216-229. doi: 10.1016/j.virol.2017.10.012. Epub 2017 Dec 1.

Abstract

Junín arenavirus infections are associated with high levels of interferons in both severe and fatal cases. Upon Junín virus (JUNV) infection a cell signaling cascade initiates, that ultimately attempts to limit viral replication and prevent infection progression through the expression of host antiviral proteins. The interferon stimulated gene (ISG) viperin has drawn our attention as it has been highlighted as an important antiviral protein against several viral infections. The studies of the mechanistic actions of viperin have described important functional domains relating its antiviral and immune-modulating actions through cellular lipid structures. In line with this, through silencing and overexpression approaches, we have identified viperin as an antiviral ISG against JUNV. In addition, we found that lipid droplet structures are modulated during JUNV infection, suggesting its relevance for proper virus multiplication. Furthermore, our confocal microscopy images, bioinformatics and functional results also revealed viperin-JUNV protein interactions that might be participating in this antiviral pathway at lipid droplet level. Altogether, these results will help to better understand the factors mediating innate immunity in arenavirus infection and may lead to the development of pharmacological agents that can boost their effectiveness thereby leading to new treatments for this viral disease.

Keywords: Junín virus; Lipids droplets; Viperin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Hemorrhagic Fever, American / genetics
  • Hemorrhagic Fever, American / immunology*
  • Hemorrhagic Fever, American / virology
  • Humans
  • Interferons / genetics
  • Interferons / immunology
  • Junin virus / chemistry
  • Junin virus / genetics
  • Junin virus / immunology
  • Junin virus / physiology*
  • Lipid Droplets / immunology
  • Lipid Droplets / virology*
  • Nucleoproteins / chemistry
  • Nucleoproteins / genetics
  • Nucleoproteins / immunology
  • Protein Domains
  • Proteins / chemistry
  • Proteins / genetics
  • Proteins / immunology*
  • Virus Replication

Substances

  • Nucleoproteins
  • Proteins
  • RSAD2 protein, human
  • Interferons