N-Glycans on the Rift Valley Fever Virus Envelope Glycoproteins Gn and Gc Redundantly Support Viral Infection via DC-SIGN

Viruses. 2016 May 23;8(5):149. doi: 10.3390/v8050149.

Abstract

Rift Valley fever is a mosquito-transmitted, zoonotic disease that infects humans and ruminants. Dendritic cell specific intercellular adhesion molecule 3 (ICAM-3) grabbing non-integrin (DC-SIGN) acts as a receptor for members of the phlebovirus genus. The Rift Valley fever virus (RVFV) glycoproteins (Gn/Gc) encode five putative N-glycan sequons (asparagine (N)-any amino acid (X)-serine (S)/threonine (T)) at positions: N438 (Gn), and N794, N829, N1035, and N1077 (Gc). The N-glycosylation profile and significance in viral infection via DC-SIGN have not been elucidated. Gc N-glycosylation was first evaluated by using Gc asparagine (N) to glutamine (Q) mutants. Subsequently, we generated a series of recombinant RVFV MP-12 strain mutants, which encode N-to-Q mutations, and the infectivity of each mutant in Jurkat cells stably expressing DC-SIGN was evaluated. Results showed that Gc N794, N1035, and N1077 were N-glycosylated but N829 was not. Gc N1077 was heterogeneously N-glycosylated. RVFV Gc made two distinct N-glycoforms: "Gc-large" and "Gc-small", and N1077 was responsible for "Gc-large" band. RVFV showed increased infection of cells expressing DC-SIGN compared to cells lacking DC-SIGN. Infection via DC-SIGN was increased in the presence of either Gn N438 or Gc N1077. Our study showed that N-glycans on the Gc and Gn surface glycoproteins redundantly support RVFV infection via DC-SIGN.

Keywords: DC-SIGN; Gc; Gn; L-SIGN; N-glycosylation; Rift Valley fever virus; sequon.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Cell Adhesion Molecules / metabolism*
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Humans
  • Jurkat Cells
  • Lectins, C-Type / metabolism*
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Polysaccharides / metabolism*
  • Receptors, Cell Surface / metabolism*
  • Receptors, Virus / metabolism*
  • Rift Valley fever virus / genetics
  • Rift Valley fever virus / physiology*
  • Viral Structural Proteins / genetics
  • Viral Structural Proteins / metabolism*
  • Virus Attachment*

Substances

  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Glycoproteins
  • Lectins, C-Type
  • Mutant Proteins
  • Polysaccharides
  • Receptors, Cell Surface
  • Receptors, Virus
  • Viral Structural Proteins