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

Inaia Phoenix,Victor Carpio,Matthew Huante,Terence Hill,Nandadeva Lokugamage,Olga Slack,Alexander Freiberg,Tetsuro Ikegami,Shoko Nishiyama

doi:10.3390/v8050149

Inaia Phoenix, Victor Carpio + Show 7 more

Open Access

https://doi.org/10.3390/v8050149

Copy DOI

Journal: Viruses	Publication Date: May 23, 2016
Citations: 68	License type: CC BY 4.0

Affiliation: The University of Texas Medical Branch at Galveston

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.

Highlights

Rift Valley fever (RVF) is a mosquito-borne, viral disease endemic to Africa and is characterized by high rates of abortion, fetal deformities, and high rates of newborn mortality, in sheep, goats, and cattle [1]
The Rift Valley fever virus (RVFV) Gc N1035 could be aligned with Sandfly fever Sicilian virus (SFSV) (N1180), Toscana virus (TOSV) (N1180), and Punta Toro virus (PTV) (N1161), while the sequon corresponding to RVFV N794 was present in SFSV, and TOSV Gc, but not in PTV Gc
These results indicate the evolutional conservation of N794 and N1035 among RVFV, Sicilian, Naples serocomplexes, and the

Summary

Introduction

Rift Valley fever (RVF) is a mosquito-borne, viral disease endemic to Africa and is characterized by high rates of abortion, fetal deformities, and high rates of newborn mortality, in sheep, goats, and cattle [1]. Humans can be infected through close contact with the body fluids of infected animals or from the bites of infected mosquitoes [2]. Human RVF is typically characterized by a self-limiting febrile illness (e.g., biphasic fever, severe headaches, muscle pain, or nausea). Viruses 2016, 8, 149 some patients may develop more severe disease, such as lethal hemorrhagic fever, neurologic disorders, or blindness [3]. RVF is caused by Rift Valley fever virus (RVFV), which belongs to the genus Phlebovirus of the family Bunyaviridae. Because of the major social and economic impacts of the disease in both public health and agriculture, RVFV is classified as a Category A Priority Pathogen by National

Objectives

Methods

Results

Discussion

Conclusion