N-glycans on the rift valley fever virus envelope glycoproteins Gn and Gc redundantly support viral infection via DC-SIGN

Inaia Phoenix, Shoko Nishiyama, Nandadeva Lokugamage, Terence E. Hill, Matthew B. Huante, Olga A.L. Slack, Victor H. Carpio, Alexander N. Freiberg, Tetsuro Ikegami

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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.

Original languageEnglish (US)
JournalViruses
Volume8
Issue number5
DOIs
StatePublished - May 23 2016

Keywords

  • DC-SIGN
  • Gc
  • Gn
  • L-SIGN
  • N-glycosylation
  • Rift Valley fever virus
  • Sequon

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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