Evidence that Processing of the Severe Fever with Thrombocytopenia Syndrome Virus Gn/Gc Polyprotein Is Critical for Viral Infectivity and Requires an Internal Gc Signal Peptide

PLoS One. 2016 Nov 17;11(11):e0166013. doi: 10.1371/journal.pone.0166013. eCollection 2016.

Abstract

The severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging, highly pathogenic bunyavirus against which neither antivirals nor vaccines are available. The SFTSV glycoproteins, Gn and Gc, facilitate viral entry into host cells. Gn and Gc are generated from a precursor protein, Gn/Gc, but it is currently unknown how the precursor is converted into the single proteins and whether this process is required for viral infectivity. Employing a rhabdoviral pseudotyping system, we demonstrate that a predicted signal sequence at the N-terminus of Gc is required for Gn/Gc processing and viral infectivity while potential proprotein convertase cleavage sites in Gc are dispensable. Moreover, we show that expression of Gn or Gc alone is not sufficient for host cell entry while particles bearing both proteins are infectious, and we provide evidence that Gn facilitates Golgi transport and virion incorporation of Gc. Collectively, these results suggest that signal peptidase liberates mature Gc from the Gn/Gc precursor and that this process is essential for viral infectivity and thus constitutes a potential target for antiviral intervention.

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Cell Line
  • Endoplasmic Reticulum / metabolism
  • Gene Expression
  • Glycoproteins
  • Golgi Apparatus / metabolism
  • Humans
  • Phlebotomus Fever / virology*
  • Phlebovirus / pathogenicity
  • Phlebovirus / physiology*
  • Polyproteins / chemistry
  • Polyproteins / genetics
  • Polyproteins / metabolism*
  • Protein Precursors / genetics
  • Protein Precursors / metabolism
  • Protein Sorting Signals*
  • Protein Transport
  • Proteolysis
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / metabolism*
  • Virus Assembly
  • Virus Internalization

Substances

  • Glycoproteins
  • Polyproteins
  • Protein Precursors
  • Protein Sorting Signals
  • Viral Envelope Proteins

Grants and funding

SP was supported by the Leibniz Association (Graduate School Emerging Infectious Diseases). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.